The definitive treatment of stage-III colon cancer is surgery and adjuvant chemotherapy. A combined assessment of pre-operative and post-adjuvant chemotherapy carcinoembryonic antigen (CEA) levels may better prognosticate early recurrence and survival.

A cohort of patients who underwent surgery and adjuvant chemotherapy was assessed. The CEA-Square (CEA2) score was defined as the multiplication of preoperative and post-adjuvant chemotherapy CEA levels and was grouped as "≤25(ng/mL)2" and ">25(ng/mL)2.

Among the 432 patients,137 were eligible. CEA2 score (>25 vs ​≤ ​25 (ng/mL)2) was significantly prognostic for early recurrence (34.5 ​% vs. 14.3 ​%, log-rank, p ​< ​0.001). In the multivariable analysis, only the CEA2 score remained associated with early recurrence [HR:3.375, (95 ​% CI:1.488-7.655), p ​= ​0.004]. In a median follow-up of 37.5 months (2.5-101.0), a high CEA2 score [>25 (ng/mL)2] was significantly associated with a worse OS (log-rank, p ​< ​0.001).

CEA2 is a simple, practical score combining prognostic values of preoperative and post-adjuvant chemotherapy CEA levels.

A 64-year-old man with a history of surgery for rectal cancer and colon cancer was referred for a hepatic mass identified on computed tomography (CT). He was diagnosed with unresectable intrahepatic cholangiocarcinoma (ICC) with perihilar and para-aortic lymph node metastases. After 4 cycles of gemcitabine and cisplatin combination therapy (GC therapy), follow-up CT showed slight enlargement of the primary tumor and a slight increase in carbohydrate antigen (CA) 19-9. Genetic testing was performed during GC therapy based on the strong family history of cancer. Germline pathogenic variant in MLH1 was identified, leading to the diagnosis of Lynch syndrome (LS) with mismatch repair deficiency (dMMR: loss of MLH1/PMS2). Durvalumab was added to GC therapy following regulatory approval in Japan. A significant reduction in tumor size and CA19-9 was observed after only two cycles of GC and durvalumab therapy. Continuous improvement was observed, and conversion surgery involving liver resection, partial inferior vena cava resection, and perihilar and para-aortic lymph nodes dissection was performed with curative intent. No malignant cells were found in any of the resected specimens, consistent with pathological complete response.

Tumor mutations and the composition of the tumor microenvironment have prognostic and therapeutic significance in colorectal cancer (CRC). However, immunotherapy remains a challenge for patients with proficient mismatch repair (pMMR) CRC. In this paper, the association between tumor-infiltrating lymphocytes (TILs) and tumor mutations on survival outcomes in patients with localized pMMR CRC was examined.

A systematic review of the literature and a meta-analysis were conducted in accordance with the PRISMA guidelines. The literature search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The outcomes of interest were overall survival, disease-free survival, and cancer-specific survival. The risk of bias was assessed through the Newcastle-Ottawa Scale and the quality of the cumulative evidence was evaluated through the modified GRADE approach.

In total, 8498 articles were screened for eligibility and 44 articles were included in the meta-analysis with 33,704 patients in total. Patients with high infiltration of any TILs showed significantly improved overall survival (HR = 0.57, 95 % CI: 0.49-0.67, I2: 0 %), especially for the subgroup of CD3 + (HR = 0.52, 95 % CI: 0.38-0.71, I2: 0 %) and CD8 + (HR = 0.60, 95 % CI: 0.37-0.99, I2: 10 %) TILs. Patients with BRAF mutation (HR = 2.68, 95 % CI: 1.47-4.89, I2: 83 %) and KRAS mutation (HR = 1.25, 95 % CI: 1.18-1.33, I2: 0 %) showed decreased overall survival.

High infiltration of TILs, especially CD3 + and CD8 + , was associated with significantly improved survival, while BRAF and KRAS mutations were correlated with worse survival outcomes for patients with non-metastatic pMMR CRC.

Gastrointestinal cancers account for approximately one-fourth of all cancer cases and one-third of all tumor-related deaths worldwide. For the most frequent gastrointestinal tumor entities including colorectal, gastric, esophageal, and liver cancer, the incidence is expected to increase by more than 50% until 2040. While most gastrointestinal cancers are diagnosed beyond the age of fertility and predominantly in men, the increasing incidence of gastrointestinal malignancies in patients below the age of fifty suggests a growing importance in women of childbearing age. While localized cancers in pregnant women can either be monitored or treated surgically, more advanced stages might require radio- or chemotherapy to control tumor growth until delivery. Under these circumstances, critical decisions have to be made to preserve maternal health on the one side and minimize harm to the infant on the other side.

Here we summarize data from case reports, meta-analyses, and registries of women undergoing radio- or chemotherapy during pregnancy and provide guidance for therapeutic decision-making in pregnant women suffering from gastrointestinal cancers.

After the first trimester, most chemotherapeutic regimens can be safely administered to pregnant patients with gastrointestinal cancers. With appropriate safety measures, both radiotherapy and radiochemotherapy can be applied to pregnant patients with rectal cancers.

In the era of precision oncology, systemic therapies for colon cancer are becoming increasingly biomarker-led, with implications for patients in the neoadjuvant, adjuvant and metastatic settings. As the landscape for colon cancer treatment evolves and becomes more complex, it is important that all members of the multidisciplinary team keep abreast of developments to ensure the most effective care is delivered to patients. As core members of the colorectal multidisciplinary team, Radiologists play a central role throughout the patient journey. This review serves as an educational summary of current and emerging treatment pathways in colon cancer, standards for biomarker testing, mechanisms of action for key drugs, important treatment-related complications, relevant tumour biology that underpins patterns of disease and treatment response, and the specific implications systemic therapies have for cancer imaging and Radiologists. We also highlight the increasing role for radiology in patient stratification and the importance of imaging biomarkers. It is crucial that Radiologists understand the current landscape of colon cancer treatment and emerging strategies on the horizon in clinical trials. Only through engagement across the wider multidisciplinary team will we deliver true personalised medicine for patients with colon cancer.

The role of adjuvant chemotherapy (adj-CT) in stage II colon cancer remains controversial. Circulating tumor DNA (ctDNA) is a promising biomarker for detecting minimal residual disease (MRD) and predicting recurrence. This systematic review and meta-analysis evaluated the prognostic value of ctDNA in stage II colorectal cancer (CRC), focusing on postoperative detection, post adj-CT outcomes, and dynamic surveillance. A literature search identified studies correlating ctDNA positivity in stage II CRC with recurrence risk, recurrence-free survival (RFS), and disease-free survival (DFS). Seven studies met the inclusion criteria. Postoperative ctDNA positivity significantly increased the risk of recurrence (pooled risk ratio [RR:] 3.66; 95% confidence interval [CI]: 1.25-10.72; p = 0.002). CtDNA positivity after adj-CT was strongly associated with poor survival, while dynamic ctDNA monitoring detected recurrence earlier than conventional methods, including carcinoembryonic antigen (CEA) and imaging. CtDNA is a robust prognostic biomarker in stage II CRC, enabling personalized treatment. High-risk ctDNA-positive patients may benefit from intensified therapy, while ctDNA-negative patients could avoid unnecessary treatments. However, the standardization of detection methods and large-scale validation studies are needed before integrating ctDNA into routine clinical practice as a non-invasive, dynamic tool for personalized care.

A 3-month adjuvant treatment regimen with capecitabine and oxaliplatin (CAPOX) for high-risk stage II (T4N0) and stage III (node-positive) colon cancer was implemented in the Netherlands in 2017. The IDEA trial showed a clinically irrelevant difference in long-term outcomes in combination with a substantial decrease in toxicity in comparison with a 6-month regimen. A significantly increased dose intensity was observed in the 3-month arm, which might be essential to achieve optimal long-term outcomes. Hence, the aim of the present study was to evaluate if a similar dose intensity could be achieved in patients treated with adjuvant CAPOX for 3 months in daily practice.

Patients scheduled for 3 months of adjuvant CAPOX for high-risk stage II or stage III colon cancer were selected from the Netherlands Cancer Registry. The number of administered cycles and the daily cumulative dose of capecitabine and oxaliplatin were extracted from the medical files. Relative dose intensity (RDI) was determined by comparing the administered dose intensity with the standard dose intensity.

In total, 802 (80.0%) of the 1002 patients completed 4 cycles of CAPOX. The overall mean RDI of adjuvant treatment was 82.9% for capecitabine, and 83.8% for oxaliplatin, based on the combination of dose reductions and omitting cycles.

One out of 5 patients did not complete 4 cycles of CAPOX. The administered dose of capecitabine and oxaliplatin in the first year after the update of the guideline was lower than the advised dose for the 3-month CAPOX regimen, and the administered dose in the IDEA study. The impact on long-term oncological outcomes should be awaited.

Standard adjuvant treatment of stage III colon cancer (CC) is fluoropyrimidine with oxaliplatin. Recently, stage III was subdivided into low-risk (T1-3, N1) and high-risk (T4 and/or N2), with the benefit of adding oxaliplatin varying across these substages. In this study, we aimed to assess the impact of oxaliplatin on survival outcomes in subdividing stage III CC patients based on T and N staging.

A total of 4942 stage III CC patients were pooled from the three randomized pivotal trials of oxaliplatin. Kaplan-Meier curves, Cox models stratified by study, and interaction tests were used to assess the oxaliplatin effect across subgroups based on T and N stages. The primary endpoint was overall survival (OS).

The prevalence of tumor stages was T1-2 12.4%, T3 74.4%, and T4 13.1%; nodal stages were N1 64.7% and N2 35.3%. A significant OS benefit from oxaliplatin was seen only in T3 (5-year OS = 77.2% versus 73.0%, P < 0.001): T3N1 (hazard ratio 0.72, 95% confidence interval 0.62-0.85, P < 0.001) and T3N2 (hazard ratio 0.81, 95% confidence interval 0.69-0.95, P = 0.010). No benefit was observed for T1-2 (5-year OS = 87.8% versus 88.7%, P = 0.644) or T4 patients (5-year OS = 62.6% versus 60.2%, P = 0.648). Subgroup analysis revealed a significant interaction between T stage and the effect of oxaliplatin treatment on OS, whereas no such interaction was observed for N stage.

Our analysis revealed that oxaliplatin-based chemotherapy offers a significant survival benefit in stage III CC patients with T3 tumors. In contrast, no survival benefit was observed for T1-2 or T4 patients. These results suggested that T stage plays a more crucial role than N stage in predicting treatment benefit, highlighting the need for tailored treatment strategies based on tumor characteristics.

Based on the International Duration Evaluation of Adjuvant Chemotherapy analysis, 3 months of adjuvant chemotherapy with capecitabine and oxaliplatin (CAPOX) is an option for stage III colorectal cancer (colorectal cancer [CRC]), with cost and toxicity benefits. We examined the patterns of uptake of CAPOX versus fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and chemotherapy duration in a contemporary real-world cohort of patients in Canada.

The provincial pharmacy database was used to identify patients with resected stage III CRC receiving adjuvant chemotherapy between January 2021 and December 2022. Demographic, tumor, and treatment information was collected and compared.

Of 452 patients, 234 (52%) and 218 (48%) were planned to receive 3 and 6 months of chemotherapy, respectively. Within the 3-month group, 226 (97%) received CAPOX. Within the 6-month group, there was a 51%-49% split between CAPOX and FOLFOX. Age >70 years (P = .039), well/moderately differentiated (P = .005), and low-risk disease (P < .0001) were significantly associated with 3 months. Performance status, ileostomy, or preexisting neuropathy did not affect treatment choice. Of patients planned for 6 months, 29% had low-risk disease, with 52% of these receiving CAPOX. Patients receiving 6 months were more likely to report neuropathy (68 v 36%, P < .0001) and to stop oxaliplatin early (54 v 31%, P < .0001). The most likely reason for early adjuvant discontinuation was neuropathy in the 6-month group and gastrointestinal toxicity in the 3-month group (P < .0001). Irrespective of duration, mean time from consult to starting chemotherapy was longer for FOLFOX versus CAPOX (24 v 19 days, P = .007).

In this contemporary cohort, 6 months chemotherapy is still being offered to patients with low-risk disease and is associated with more neuropathy. Exploration of patient preferences and resource costs may improve adoption of reduced duration adjuvant CAPOX in stage III CRC.

Background/Objective: The prognostic value of specific hot-spot mutations within KRAS, NRAS, and BRAF genes in metastatic colorectal cancer (mCRC) genes remains debatable. This study explores whether certain KRAS, NRAS, and BRAF mutations are associated with the risk of all-cause mortality in mCRC. Methods: We retrospectively analyzed records of 494 patients with mCRC treated at the University of Texas Medical Branch between January 2016 and July 2023. Data on genetic mutations and clinicopathological features were collected for this analysis. We estimated survival probabilities and conducted multivariable Cox proportional hazards regression to evaluate the impact of specific mutations on all-cause mortality risk. Results:KRAS c.35G>T (p.Gly12Val) and c.34G>T (p.Gly12Cys) mutations were significantly associated with an increased risk of all-cause mortality in the overall mCRC population and the treated mCRC subgroup. KRAS c.38G>A (p.Gly13Asp) was significantly associated with an increased risk of all-cause mortality in the treated mCRC subgroup but BRAF c.1799T>A (p.Val600Glu) was significantly associated with an increased risk of all-cause mortality in the overall mCRC population. No significant association was observed between NRAS mutations and mortality risk in mCRC, possibly due to their lower frequency or different biological effects compared to KRAS and BRAF mutations. Conclusions: These findings suggest that specific KRAS [c.35G>T (p.Gly12Val), c.34G>T (p.Gly12Cys), and c.38G>A (p.Gly13Asp)] and BRAF c.1799T>A (p.Val600Glu) mutations may have prognostic value in mCRC. However, given the single-center study design and lack of direct therapeutic implications, larger multicenter studies are needed to substantiate these results and better define the clinical relevance of these mutations.

The molecular characterization of early-stage (1-3) colorectal cancer (CRC) remains incomplete, as opposed to metastatic disease, where comprehensive genomic profiling (CGP) is routinely performed. This study aimed to characterize the genomics of stages 1-3 versus IV CRC, and the genomics of patients recurring within 1 year of diagnosis.

Patients from a de-identified CRC clinico-genomic database who received Foundation Medicine testing (FoundationOne/FoundationOne CDx) during routine clinical care at approximately 280 US cancer clinics between March 2014 and June 2023 were included. Genomic alterations (GA) were compared by Fisher's exact test.

A total of 4702 patients were included; 1902 with stages 1-3 and 2800 with stage 4 disease. Among patients with stages 1-3 disease, 546 recurred within 1 year. Patients staged 1-3 had higher prevalence of microsatellite instability (MSI-H, 11.4% vs 4.5%, P < .001), tumor mutational burden (TMB) ≥ 10 Mut/Mb (14.6% vs 6.8%, P < .001), GA in RNF43 (11.2% vs 5.7%, P < .001), MSH6 (3.9% vs 1.7%, P < .001), MLH1 (2.3% vs 0.7%, P < .001), and MSH2 (1.5% vs 0.6%, P < .01) compared to those with stage 4 disease. Patients who recurred within 1 year had higher prevalence of MSI-H (13.2% vs 4.4%, P < .001), TMB ≥ 10 Mut/Mb (16.2% vs 6.9%, P < .001), BRAF V600E (17.2% vs 7.9%, P < .003), GA in RNF43 (13.7% vs 5.3%, P < .001), MSH6 (4.2% vs 1.6%, P = .035), and BRCA1/2 (6.2% vs 3.0%, P = .030). On recurrence, more patients received targeted therapy when CGP was performed before versus after first-line therapy (43% vs 19%, P < .001).

Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.

The effectiveness of oxaliplatin (L-OHP) has been reported overseas; however, in Japan, the prognosis of colorectal cancer (CRC) patients is reported to be good, and there has been a long debate about the applicability of L-OHP combination therapy in Japan. In recent years, the results of the ACHIEVE trial have become clear, and the standard consensus in Japan establishes L-OHP combination therapy for a duration of 3 months as the adjuvant treatment for CRC.

Lynch syndrome is the most common hereditary cancer predisposition, accounting for 1-5% of colorectal cancer cases, and is driven by germline mutations in DNA mismatch repair genes. Despite established diagnostic criteria, such as the Amsterdam guidelines, Lynch syndrome remains largely underdiagnosed. To address this gap, universal tumour screening has been introduced for all newly diagnosed cases of colorectal cancer and endometrial cancer, significantly improving early detection. The surgical management of colorectal cancer in patients with Lynch syndrome remains controversial. While extended colectomy reduces the risk of metachronous colorectal cancer, surgical strategies must be carefully individualised based on patient-specific factors. Chemoprevention with aspirin has shown promise in reducing the risk of colorectal cancer, with ongoing trials investigating optimal dosing. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionised the treatment of Microsatellite Instability-High/deficient Mismatch Repair colorectal cancer, offering durable responses and significant survival benefits. In addition, the neoadjuvant use of immune checkpoint inhibitors is paving the way for non-surgical interventions, potentially transforming the management of colorectal cancer in patients with Lynch syndrome. A multidisciplinary approach and continued research are essential to optimise cancer prevention, treatment and quality of life for people with Lynch syndrome.

Colorectal cancer (CRC) represents a heterogeneous group of diseases that imposes a considerable global and national health burden. Although most CRC patients are diagnosed at an early stage and undergo potentially curative treatment, a significant proportion experience recurrence. Currently, adjuvant chemotherapy decisions are primarily based on clinicopathological characteristics, which have well-recognized limitations in accurately identifying patients harboring minimal residual disease (MRD), often resulting in unnecessary chemotherapy exposure. Circulating tumor DNA (ctDNA) has emerged as a promising surrogate marker for MRD, offering a more precise approach to identifying patients at risk of recurrence after curative-intent surgery and refining adjuvant chemotherapy decisions. Growing evidence from multiple studies has demonstrated that ctDNA outperforms traditional clinicopathological factors as a marker for MRD. This review synthesizes key studies supporting the role of ctDNA in MRD detection for CRC patients and evaluates clinical trials investigating the application of ctDNA in guiding adjuvant therapy decisions. This emerging strategy holds the potential to transform the adjuvant treatment paradigm in colorectal cancer by optimizing therapeutic precision and minimizing unnecessary treatment.

Analysis of ctDNA may enable early identification of patients likely to relapse, presenting an opportunity for early interventions and improved outcomes. Tumor-naïve plasma-only approaches for minimal residual disease (MRD) assessment accelerate turnaround time, enabling rapid treatment decisions and ongoing surveillance.

Plasma samples were obtained from 80 study participants with stage II or III colorectal cancer selected from CIRCULATE-Japan GALAXY. MRD status was assessed using a tumor-naïve ctDNA assay (xM) that integrates methylation and genomic variant data, delivering a binary call. MRD was assessed at 4 weeks postsurgery [landmark time point (LMT)] using methylation and genomic variant data and longitudinally (median, 22.1 months) using only methylation data.

At LMT, 69/80 study participants were evaluable (36 recurrent; 33 nonrecurrent). Of recurrent study participants, 22/36 had detectable ctDNA (MRD-positive) at LMT and 29/33 nonrecurrent study participants had undetectable ctDNA (MRD-negative), yielding a clinical sensitivity of 61.1% and specificity of 87.9%. Additionally, 74 study participants were evaluable for longitudinal performance with a clinical sensitivity of 83.3% and specificity of 89.5%. The median lead time from the first MRD-positive result to recurrence was 4.77 months overall, and 5.30 months for study participants with no adjuvant treatment. At 12 weeks postsurgery, MRD status strongly correlated with disease-free survival (adjusted HR, 9.69), outperforming carcinoembryonic antigen correlation (HR, 2.13).

This tumor-naïve MRD assay demonstrated clinically meaningful performance at LMT and longitudinally, accurately predicting clinical recurrence. MRD status was a stronger prognostic biomarker for disease-free survival compared with standard-of-care carcinoembryonic antigen.

Males have a higher incidence and mortality rate from colorectal cancer (CRC) compared with females. This review examines the reasons for these differences, including risk factors, screening participation, interpretation of screening tests, presentation and tumour types, pathophysiology (particularly the impact of sex hormones on tumour-related gene expression, microsatellite instability, micro-RNA expression, and the tumour microenvironment), and the efficacy and toxicity of treatment. Sex differences in hormones and body composition are responsible for some of the sexual dimorphism in CRC incidence and outcomes, particularly the pathophysiology, CRC presentation, the pharmacokinetics of cytotoxic therapies, and the impact of treatment on outcomes. However, gender differences also play a role, affecting risk factors, access to or participation in screening and treatment, and patients' experience of treatment (e.g. adverse events and sequelae). Sex and gender issues warrant further investigation in CRC to optimise treatment outcomes for patients.

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018. Patients treated with and without adjuvant chemotherapy were matched based on tumor location, T- and N-stage (n = 522). Tumor material was available for 464 patients, with successful RNA extraction and CMS subtyping achieved in 390 patients (surgery alone group: 192, adjuvant chemotherapy group: 198). In the overall cohort, CMS4 was associated with poorest prognosis (HR 1.55; p = .03). Multivariate analysis revealed favorable RFS for the adjuvant chemotherapy group in CMS1, CMS2, and CMS4 tumors (HR 0.19; p = .01, HR 0.27; p < .01, HR 0.19; p < .01, respectively), while no significant difference between treatment groups was observed within CMS3 (HR 0.68; p = .51). CMS subtyping in this non-randomized cohort identified patients with poor prognosis and patients who may not benefit significantly from adjuvant chemotherapy.

Colorectal cancer primarily affects older adults and poses treatment challenges due to age-related comorbidities and frailty, which hinder surgical and chemotherapy options for many elderly patients. This study aims to analyze treatment and disease patterns in elderly colorectal cancer patients, aged over 80 years old, to inform personalized therapies that accommodate their unique clinical needs and improve their outcomes.

The medical records of all patients aged 80 years old and above, and those aged 65 to 75 years old, who were diagnosed with colorectal cancer at a cancer center in Canada over a seven year period, were retrospectively reviewed.

No significant differences in the initial presentation, location, grade or stage at colorectal cancer diagnosis were observed between age groups. Patients aged 80 years old and above were less likely to receive neoadjuvant and adjuvant chemotherapy treatments for stage II disease (19.2% versus. 58.6%, p = 0.002; 7.9% versus. 40.0%, p = 0.002). There were also differences in the intensity of chemotherapy received and the frequency of dose reductions (76.0% vs. 10.0%, p = 0.0001), neoadjuvant and adjuvant radiation therapy (34.6% vs. 65.5%, p = 0.02) and surgical management (83.7% vs. 95.3%, p = 0.006). Despite these differences in treatments, recurrence rates were not statistically significant between the two groups. However, overall survival was reduced in the older age group.

Treatment plans for patients aged 80 years old and above should be tailored to the patient's colorectal cancer presentation, comorbidity status and life expectancy, weighing the impact of cancer treatments on the patient's short- and long-term outcomes.

A shorter duration of oxaliplatin adjuvant chemotherapy has recently emerged as a potential option for patients with high-risk stage II and low-risk stage III (T1-3N1) colon cancer (CC). The present study aimed to elucidate the risk factors for recurrence in these patient populations and to identify the appropriate indications for shortened treatment durations. The present study retrospectively analyzed 396 patients who underwent curative surgery for pathological T4N0 or stage III CC, followed by adjuvant chemotherapy, at two institutes. Overall, 234 patients with T4N0 and low-risk stage III CC were categorized into the low-risk group and 162 patients with high-risk stage III CC into the high-risk group. The 3-year relapse-free survival rate was significantly higher in the low-risk group than in the high-risk group. Multivariate Cox model analysis of the low-risk group revealed that high preoperative serum levels of carcinoembryonic antigen (CEA) and incomplete 6-month adjuvant chemotherapy with oxaliplatin were independent poor prognostic factors. The prognosis of patients in the low-risk group who had abnormal CEA levels and did not complete the 6-month adjuvant treatment with oxaliplatin was similar to that of patients in the high-risk group. However, the prognosis of patients in the low-risk group with high CEA levels improved with a 6-month adjuvant treatment with oxaliplatin to a similar level to that of all patients with low CEA levels in the low-risk group. In conclusion, the present study suggested that the duration of adjuvant chemotherapy with oxaliplatin should not be shortened in patients with high preoperative CEA levels, even in the low-risk group.

To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer (CRC).

Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge. Some cancer types are less responsive to immunotherapy, and the heterogeneity in responses within cancer types is poorly understood. Clinical characteristics of the patient, the timing of immunotherapy in relation to surgery, diversities in the immune responses, clonal heterogeneity, different features of the tumor microenvironment, and genetic alterations are some factors among many that may influence the efficacy of immunotherapy.

In this narrative review, we describe the major types of immunotherapy used to treat localized CRC. Furthermore, we discuss the prediction of response to immunotherapy in relation to biomarkers and radiologic assessment. Finally, we consider the future perspectives of clinical implications and response patterns, as well as the potential and challenges of neoadjuvant immunotherapy in localized CRC.

Establishing mismatch repair (MMR) status at the time of diagnosis is central to the potential use of neoadjuvant immunotherapy, in particular immune checkpoint inhibitors, in localized CRC. To date, efficacy is primarily seen in patients with deficient MMR status and polymerase epsilon mutations, although a small group of patients with proficient MMR does respond. In conclusion, neoadjuvant immunotherapy shows promising complete response rates, which may open a future avenue of an organ-sparing watch-and-wait approach for a group of patients.

While specific elements of naturopathic medicine, such as botanical medicines and lifestyle interventions, have supporting evidence, there is limited quantitative data confirming its effectiveness as a comprehensive, whole-person medical approach for patients with metastatic colorectal cancer (CRC).

This study aims to retrospectively evaluate the integration of naturopathic modalities, including modulated electrohyperthermia (mEHT), into the standard of care for metastatic CRC. We compare survival outcomes between patients at the Integrated Health Clinic (IHC) and a matched control group from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, a de-identified, publicly available cancer registry in the United States.

A retrospective chart review was conducted for 131 IHC patients diagnosed with stage IV CRC and treated with mEHT between 2010 and 2021. These patients were matched with 262 controls from the SEER database using propensity score matching. The primary outcome was overall survival, with time zero defined as the first IHC treatment date (with controls assigned the time zero of their matched IHC patient) to account for immortal time bias. Survival analysis was conducted using a Kaplan-Meier curve, log-rank test, and Cox proportional-hazards model.

The overall survival analysis did not achieve a statistically significant difference (HR = .76; 95% CI: .57-1.01) between the IHC (median survival time: 29 month) and SEER groups (median survival time: 18 months). Incorporating time-varying effects, the hazard ratio (HR) for the IHC group compared to the SEER group was .63 (95% CI: .46-.86) for survival <36 months, indicating a lower hazard of early mortality in the IHC group. Moreover, IHC patients who initiated treatment within 90 days of diagnosis had significantly improved survival compared to their matched controls (HR = .45; 95% CI: .28-.70).

This study provides evidence that integrative naturopathic treatment, including mEHT, can significantly improve survival outcomes for CRC patients in the first 36 months post-treatment and when initiated within 90 days of diagnosis.

The adjuvant treatment for stage III colon cancer (CC) is chemotherapy combining fluoropyrimidine (FP) and oxaliplatin (OX). FP regimen plus OX (FPOX) may benefit in high-risk stage II CC. We performed a pooled analysis of pivotal MOSAIC and C-07 studies evaluating FPOX for the treatment of high-risk stage II CC according to prognostic factors, number of high-risk factors, and current clinicopathologic risk classification on the basis of T stage, tumor perforation, and number of lymph nodes examined.

One thousand five hundred and ninety-five patients with stage II CC receiving FP or FPOX were pooled. The overall survival (OS) benefit of OX was analyzed using Kaplan-Meier curves and unadjusted Cox models stratified by study. Three thousand and fifty-nine patients with stage III CC were used only for interaction tests between the allocated chemotherapy and stage.

In the pooled analysis of stage II patients, independent prognostic factors in multivariable analysis were sex, age, perforation/obstruction, and tumor sidedness. There was a significant interaction in OS between stage and allocated chemotherapy with hazard ratios (HRs) of 1.03 for stage II (95% CI, 0.82 to 1.29; P = .813) and 0.82 for stage III (95% CI, 0.73 to 0.92; P = .001; Pint = .073). There was no benefit from the addition of OX to FP for any of the prognostic factors. The number of high-risk factors tested was not predictive of OX benefit. According to the currently agreed clinicopathologic risk classification, no OS benefit of OX was observed, as HR was 0.86 (95% CI, 0.63 to 1.18; P = .349).

No OS benefit of adjuvant OX was found in high-risk stage II CC, regardless of the definition used to characterize tumors as having a high risk for recurrence. Hence, our analysis suggests that OX should not be the standard of care for adjuvant chemotherapy for stage II CC, even in high-risk patients.

This study examined the association between deficient mismatch repair (dMMR) versus proficient MMR (pMMR) status and overall survival and disease-free survival in patients with localized colorectal cancer.

Several distinctions exist between patients with dMMR and pMMR colorectal cancer. However, the impact on prognosis is yet to be investigated in large-scale cohort studies.

In this cohort study, we included patients who underwent curative-intent surgery for localized colorectal cancer between 2009 and 2020. Patients were identified in the Danish Colorectal Cancer Group database and patient-level data were extracted from 6 registry databases. After inclusion, patients with dMMR status were matched 1:1 to patients with pMMR status using an estimated propensity score.

After matching, 5994 patients were included. The patients had a median age of 74 years and a median follow-up of 4.1 years. There was no significant association between mismatch repair (MMR) status and overall survival (hazard ratio, 0.91; 95% confidence interval [CI], 0.81-1.03) or disease-free survival (hazard ratio, 0.89; 95% CI, 0.78-1.01). However, the restricted 5-year mean disease-free survival time, calculated due to violation of the proportional hazards assumption, showed a significant absolute difference of 0.13 years (95% CI, 0.03-0.23; P = 0.01) in favor of the dMMR group.

No significant association with overall survival was found according to MMR status. dMMR status was, however, found to be associated with marginally improved disease-free survival compared to pMMR status in patients with localized colorectal cancer undergoing curative-intent surgery.

This manuscript reports the results of the Indian Network for Development of Peritoneal Surface Oncology and Indian Society of Peritoneal Surface Malignancies (INDEPSO-ISPSM) consensus that aimed to provide recommendations for some important aspects management of patients with colorectal peritoneal metastases (CPM) and address some issues unique to India.

The modified Delphi technique was used with two rounds of voting. There were 29 questions on nine main topics-the role of cytoreductive surgery (CRS), patient selection for CRS, preoperative workup, role of systemic chemotherapy (SC), CPM with other visceral metastases, molecular profile, hyperthermic intraperitoneal chemotherapy (HIPEC) and other modalities of intraperitoneal chemotherapy (IPC), prophylactic/preventive strategies, and surveillances after CRS. A consensus was achieved if anyone option received >70 votes (strong consensus >90%).

Forty-eight surgical (n = 41) and gastrointestinal (n = 7) oncologists were invited; 44 agreed to participate. The response rate was 95.4% (42/44) in round 1 and 93.1% (41/44) in round 2. Overall, a consensus was achieved on 23/29 (79.3%) questions (strong consensus on 6/29 [20.6%]). The panel strongly recommended considering surgery for limited CPM with limited liver metastases (92.5%), not altering the surgical approach in patients with KRAS mutations (91.67%), and limiting the use of IPC for unresectable CPM outside clinical trials (95%). Adjuvant SC was recommended for all patients undergoing CRS (89.47%). CRS is a therapeutic option for selected patients with CPM including those with metachronous CPM (79.49) and signet ring cell cancers (76.92%). HIPEC was recommended outside clinical trials only for patients with peritoneal cancer index 11-15(80%).

The panel recommended CRS for most indications but was very selective in recommending HIPEC and IPC outside clinical trials. These recommendations should be a useful resource in clinical decision making for clinicians treating CPM in India and regions with a similar sociodemographic background.

Stage II colon cancer (CC) exhibits considerable prognostic heterogeneous. Our objective was to assess survival but also the prognosis impact of microsatellite instability (MSI) in patients with stage IIC (T4bN0M0) CC.

We conducted a retrospective observational study including all patients who had primary stage IIC CC resection between 2010 and 2020 in 2 expert centers. The primary endpoint was overall survival (OS) and disease-free survival (DFS) and time-to-relapse (TTR) were secondary endpoints.

Sixty-six patients, median age of 74 years [30-95], were included, with 37.9% presenting MSI (n = 25). Organ invasion involved the last ileal loop (n = 17), another colonic segment (n = 15), omentum (n = 13), visceral peritoneum (n = 13), and the bladder (n = 4). Surgical quality criteria showed complete monobloc resection in all patients and 93.9% R0 resection. After a median follow-up of 5 years [3.5-6.6], the entire population showed a 5-year OS of 65.2% [53.0-80.3] and 5-year DFS of 53.5% [41.1-69.6], with 18.9% [6.8-29.4] experiencing relapses at 5 years. The MSI phenotype correlated with improved 5-year OS (75.5% [56.5-100] vs. 59.5% [44.9-79.0], HR 0.41 [0.17-0.99]; P = .04), but DFS and TTR did not differ. Adjuvant chemotherapy was administered to 34.9% of patients. Univariate analysis identified age > 65 years, MSI status, and the number of nodes as factors associated with OS.

These data underline, in relation to a low rate of relapse, the lack of consensus regarding the appropriate indication for adjuvant chemotherapy in this high-risk stage II population.

Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.

Biomarkers have revolutionized the management of colorectal cancer (CRC), facilitating early detection, prevention, personalized treatment, and minimal residual disease (MRD) monitoring. This review explores current CRC screening strategies and emerging biomarker applications.

We summarize the landscape of non-invasive CRC screening and MRD detection strategies, discuss the limitations of the current approaches, and highlight the promising potential of novel biomarker solutions. The fecal immunochemical test remained the cornerstone of CRC screening, but its sensitivity has been improved by assays that combined its performance with other stool analytes. However, their sensitivity for advanced adenomas and the patient compliance both remain suboptimal. Blood-based tests promise to increase compliance but require further refinement to compete with stool-based biomarker tests. The ideal scenario involves leveraging blood tests to increase screening participation, and simultaneously promote stool- and endoscopy-based screening among those who are compliant. Once solely reliant on upfront surgery followed by stage and pathology-driven adjuvant chemotherapy, the treatment of stage II and III colon cancer has undergone a revolutionary transformation with the advent of MRD testing after surgery. A decade ago, the concept of using a post-surgical test instead of stage and pathology to determine the need for adjuvant chemotherapy was disruptive. Today, a blood test may be more informative of the need for chemotherapy than the stage at diagnosis.

Biomarker research is not just improving, but bringing a transformative change to CRC clinical management. Early detection is not just getting better, but improving thanks to a multi-modality approach, and personalized treatment plans are not just becoming a reality, but a promising future with MRD testing.

Adjuvant chemotherapy (AC) for stage III disease is recognized as a standard treatment and is routinely performed in patients with colon cancer (CC). However, the recommendation for AC is mainly based on studies performed in past environments, where D3 lymphadenectomy was not routinely performed.

We retrospectively analyzed CC patients who underwent curative resection with D3 lymphadenectomy in Keio Surveillance Epidemiology and End Results (K-SEER) database. After patients were divided into AC and non-AC groups, propensity score matching (PSM) was performed to match the two groups.

After PSM, 84 patients were included in each group. There were no significant differences between the AC and non-AC groups in the 5-year cancer-specific survival (CSS; 88.01% vs. 81.46%, p = 0.295) and 5-year recurrence-free survival (RFS; 69.57 vs. 70.08%, p = 0.820), respectively. In the subgroup analysis, AC improved both the CSS [hazard ratio (HR)0.273; 95% confidence interval (CI) 0.094-0.797, p = 0.017] and RFS (HR 0.376; 95% CI 0.174-0.806, p = 0.012) only for tumors with N2 disease compared to non-AC.

The current indications for AC in patients with CC after D3 lymphadenectomy should be reconsidered. It is possible that AC is appropriate only for stage III CC patients with N2 disease.

Circulating tumor DNA (ctDNA) represents a powerful measure of minimal residual disease (MRD) in colorectal cancer (CRC). Although immunotherapy has been widely established in metastatic CRC that is mismatch repair deficient or microsatellite instability-high (dMMR/MSI-H), its role in non-metastatic CRC is rapidly evolving. In resected, dMMR/MSI-H stage II CRC, adjuvant fluoropyrimidine has no benefit and is not recommended. There is growing evidence to suggest diminished benefit from neoadjuvant chemotherapy and chemoradiation in localized CRC that is dMMR/MSI-H. We present two cases of dMMR/MSI-H stage III CRC treated with definitive surgery wherein adjuvant oxaliplatin-based chemotherapy led to a failure to clear postoperative plasma ctDNA levels, prompting a change to immune checkpoint blockade with pembrolizumab and resultant ctDNA clearance. We illustrate that chemotherapy may achieve suboptimal disease control in localized colon cancer that is dMMR/MSI-H, while plasma ctDNA offers a window of opportunity to gauge the efficacy of oxaliplatin-based adjuvant chemotherapy to clear microscopic disease in resected, dMMR/MSI-H stage III colon cancer. These findings are important to contextualize given that relapse is inevitable with failure to clear MRD in the postoperative stage I-III CRC setting whereby chemotherapy remains the standard adjuvant therapy in resected, dMMR/MSI-H stage III colon cancer.

The purpose of this study was to investigate the effects of postoperative complications on long-term survival after laparoscopic surgery for resectable colorectal cancer.

We retrospectively included 204 patients who underwent laparoscopic surgery for colorectal cancer from January 2016 to June 2020.

Overall, 68 (33.3%) patients had postoperative complications, twelve (17.6%) of which were classified as Clavien-Dindo class 3a or higher. The 5-year overall survival rate of the non-complication and complication groups were 93.0% and 81.7%, respectively (p = 0.048; Kaplan-Meier analysis and log-rank test), and those among patients with stage III disease were 87.0% and 61.3%, respectively (p = 0.045). The 5-year disease-free survival rates were 85.6% and 77.4%, respectively (p = 0.042). Multivariable Cox proportional-hazards analysis revealed that nodal stage (hazard ratio, 8.392; 95% confidence interval, 1.892-37.175; p = 0.005) was an independent prognostic factor for overall survival, and postoperative complications (hazard ratio, 2.996; 95% confidence interval, 1.076-8.340; p = 0.036) were independent prognostic factors for disease-free survival.

Postoperative complications were associated with poor oncological outcomes, especially among patients with stage III colorectal cancer, and independent prognostic factors for disease-free survival.

Colorectal cancer (CRC) has a 5-year overall survival rate of over 60%. The decrease in the rate of metastatic disease is due to screening programs and the population's awareness of healthy lifestyle. Similarly, advancements in surgical methods and the use of adjuvant chemotherapy have contributed to a decrease in the recurrence of resected disease. Before evaluating a patient's treatment, it is recommended to be discussed in a multidisciplinary tumor board. In stage II tumors, the pathologic characteristics of poor prognosis must be known (T4, number of lymph nodes analyzed less than 12, lymphovascular or perineural invasion, obstruction or perforation, poor histologic grade, presence of tumor budding) and it is mandatory to determine the MSI/MMR status for avoiding administering fluoropyridimidines in monotherapy to patients with MSI-H/dMMR tumors. In stage III tumors, the standard treatment consists of a combination of fluoropyrimidine (oral or intravenous) with oxaliplatin for 6 months although the administration of CAPOX can be considered for 3 months in low-risk tumors. Neoadjuvant treatment is not consolidated yet although immunotherapy is achieving very good preliminary results in MSI-H patients. The use of ctDNA to define the treatment and monitoring of resected tumors is only recommended within studies. These guidelines are intended to help decision-making to offer the best management of patients with non-metastatic colon cancer.

Background: Adjuvant chemotherapy (AC) for colorectal cancer (CRC) has led to substantial improvement in survival. Several clinical trials advocate the initiation of AC within 6-8 weeks of surgical resection based on evidence of improved survival with early initiation of AC. We aim to evaluate factors that predict initiation and completion of AC, subsequently improving survival. Methods: We identified 451 patients who underwent resection for CRC between 2014 and 2022. One hundred ten patients had stage II/III colorectal cancer who underwent resection followed by AC. Multivariable logistic regression analysis was performed to identify factors significantly predicting delay in AC >8 weeks. Secondary outcomes included chemotherapy completion rate, recurrence-free survival, and overall survival. Results: The final analysis included 110 patients. The median time to initiation of adjuvant chemotherapy (TIAC) was 6.9 weeks (IQR: 5.8-9.5). In total, 36.4% of patients had a delay >8 weeks to initiation of AC, and only 40% completed treatment. The surgical approach (open vs laparoscopic vs robotic) had no effect on the TIAC. On multivariable logistic regression analysis, preoperative albumin ≥3.5 (OR = .31; 95% CI: .12-.80) was an independent predictor of timely initiation of AC. Completion of AC was associated with a higher overall survival. Discussion: Preoperative nutritional status predicted delay in initiation of AC. Patients with a delay in AC beyond eight weeks had a lower rate of AC completions and worse survival. It is imperative to optimize this aspect of treatment as it correlates with survival.

Mismatch repair deficiency (dMMR) is found in approximately 15% of non-metastatic colon cancers (CCs) and is characterized by a defective DNA mismatch repair system, resulting in hypermutated and highly immunogenic tumors. Although patients with dMMR CC have limited benefit from chemotherapy, these tumors have been shown to respond exceptionally well to neoadjuvant anti-PD-1 plus anti-CTLA-4, with high rates of pathologic responses. Here, based on data from melanoma studies, we postulated a high efficacy and favorable toxicity profile of anti-PD-1 plus anti-LAG-3. In the NICHE-3 study, a total of 59 patients with locally advanced dMMR CC were treated with two 4-weekly cycles of nivolumab (480 mg) plus relatlimab (480 mg) before surgery. Pathologic response was observed in 57 of 59 (97%; 95% confidence interval (CI): 88-100%) patients, meeting the primary endpoint. Responses included 54 (92%; 95% CI: 81-97%) major pathologic responses (≤10% residual viable tumor) and 40 (68%; 95% CI: 54-79%) pathologic complete responses. With a median follow-up of 8 months (range, 2-19), one patient had recurrence of disease. The treatment displayed an acceptable safety profile, with all-grade and grade 3-4 immune-related adverse events (irAEs) occurring in 80% and 10% of patients, respectively. The most common irAEs were infusion-related reactions (29%), thyroid dysfunction (22%) and fatigue (20%). In conclusion, our results show that neoadjuvant nivolumab/relatlimab induces high rates of pathologic responses and that further investigation of this treatment in larger studies is warranted. These data add to the body of evidence in support of neoadjuvant immunotherapy regimens in dMMR CC. ClinicalTrials.gov identifier: NCT03026140 .

Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC.

Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients.

The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052).

Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Colorectal cancer remains a significant health burden in South Korea, being the third most diagnosed cancer in the country. Despite advances in treatment, patients with metastatic colorectal cancer still face limited survival rates, with resection often deemed impossible for the majority. This review discusses the current state of chemotherapy in colorectal cancer treatment, focusing on both adjuvant chemotherapy post-surgery and palliative chemotherapy for metastatic cases. The article highlights recent updates in treatment guidelines, including the use of immunotherapy and the role of circulating tumor DNA (ctDNA) in personalized medicine. The integration of these novel approaches aims to enhance treatment efficacy, improve patient survival, and reduce recurrence rates, paving the way for more tailored and effective therapeutic strategies in colorectal cancer management.

Chemotherapy tolerance weakened efficacy of chemotherapy drugs in the treating gastric cancer (GC). Banxiaxiexin decoction (BXXXD) was widely used in digestive diseases for thousands of years in Traditional Chinese medicine (TCM). In order to better treat GC, three other herbs were added to BXXXD to create a new prescription named Modified Banxiaxiexin decoction (MBXXXD). Although MBXXXD potentially treated GC by improving chemotherapy tolerance, the possible mechanisms were still unknown.

To explore the therapeutic effect of MBXXXD on GC patients and explore the possible anti-cancer mechanism.

A randomized controlled trial (n = 146) was conducted to evaluate the clinical efficacy between MBXXXD + chemotherapy (n = 73) and placebo + chemotherapy (n = 73) in GC patients by testing overall survival, progression free survival, clinical symptoms, quality of life score, tumor markers, T cell subpopulation, and adverse reactions. Network pharmacology was conducted to discover the potential mechanism of MBXXXD in treating GC. Metabolic activity assay, cell clone colony formation and mitochondrial apoptosis were detected in human GC cell lines including AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD. Multiple pathways including P53, AKT, IκB, P65, P38, ERK, JNK p-AKT, p-P65, p-P38, p-ERK and p-JNK in AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy were also detected.

MBXXXD + chemotherapy promoted overall survival and progression free survival, improved clinical symptoms and quality of life score, increased T4 lymphocyte ratio and T8 lymphocyte ratio as well as T4/T8 lymphocyte ratio, and alleviated adverse reactions in GC patients. Network pharmacology predicted multiple targets and pathways of MBXXXD in treating GC including apoptosis, P53 pathway, AKT pathway, MAPK pathway. MBXXXD inhibited cell viability, decreased cell clone colony formation, and promoted mitochondrial apoptosis by producing reactive oxygen species (ROS), promoting mitochondrial permeability transition pore (MPTP) and the cleavage of pro-caspase-3 and pro-caspase-9, and decreasing mito-tracker red Chloromethyl-X-rosamine (CMXRos) in AGS cell, KNM-45 cell and SGC7901 cell. MBXXXD up-regulated the expression of P53 and IκB, and down-regulated the expression of p-AKT, p-P65, p-P38, p-ERK, p-JNK, AKT, P65, P38, ERK and JNK AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy.

MBXXXD benefitted chemotherapy for GC by regulating multiple targets and pathways.