In recent years, the use of traditional Chinese medicine (TCM) in the treatment of cancer has received widespread attention. Treatment of tumours using TCM can effectively reduce the side effects of anti-tumour drugs, meanwhile to improve the treatment efficacy of patients. However, most of the active ingredients in TCM, such as saponins, alkaloids, flavonoids, volatile oils, etc., have defects such as low bioavailability and poor solubility in clinical application, which seriously restrict the application of TCM. Meanwhile, the encapsulation of TCM into lipid nano-delivery systems for cancer therapy has received much attention. Lipid nano-delivery systems are obtained by using phospholipids as the base material and adding other auxiliary materials under a certain preparation process, including, for example, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), microemulsions, and self-microemulsion drug delivery systems (SMEDDS), can resolve the application problems of TCM by improving the efficacy of active ingredients of TCM and reducing the toxicity of anti-tumour drugs. This paper focuses on the categories, development status, and research progress of lipid nano delivery system of TCM, aiming to provide a certain theoretical basis for further in-depth research and rational application of these systems.

Chemotherapy resistance and immunosuppression are major causes of tumor treatment failure. The polarization state of tumor-associated macrophages (TAMs) is a central regulatory hub for both processes. Traditional Chinese medicine (TCM) has the characteristics of multi-component, multi-target, and multi-pathway. It regulating M1/M2 polarization is promising due to the high plasticity of TAMs. This review comprehensively explores the anti-tumor effects of TCM active components through multiple targets such as metabolic reprogramming. The mechanism includes regulating TAM's polarization, reversing chemotherapy resistance, and modulating immunosuppression. Furthermore, we also summarize the synergistic effects of TCM multi-component and the exploration of mechanisms promoted by new technologies. While most studies are still in the preclinical stage, these insights highlight the potential of TCM as a cancer treatment and highlight avenues for future research and clinical application to improve patient outcomes.

Tumor immune escape presents a significant challenge in cancer treatment, characterized by the upregulation of immune inhibitory molecules and dysfunction of immune cells. Tumor immunotherapy seeks to restore normal anti-tumor immune responses to control and eliminate tumors effectively. The active ingredients of traditional Chinese medicine (TCM) demonstrate a variety of anti-tumor activities and mechanisms, including the modulation of immune cell functions and inhibiting tumor-related suppressive factors, thereby potentially enhancing anti-tumor immune responses. Furthermore, nano-delivery systems function as efficient carriers to enhance the bioavailability and targeted delivery of TCM active ingredients, augmenting therapeutic efficacy. This review comprehensively analyzes the impact of TCM active ingredients on the immune system and explores the synergistic application of nano-delivery systems in combination with TCM active ingredients for enhancing tumor immunotherapy.

One of the leading causes of cancer-related mortality globally is non-small cell lung cancer (NSCLC). It has become a significant public health concern due to its rising incidence rate and fatality. Tumor-associated macrophage (TAM) is important in the tumor microenvironment (TME) of NSCLC because they have an impact on the development, metastasis, and incidence of tumors. As a crucial element of the TME, TAM contributes to tumor immune evasion, facilitates tumor proliferation and metastasis, and modulates tumor angiogenesis, immunosuppression, and treatment resistance through the secretion of diverse cytokines, chemokines, and growth factors. Consequently, TAM assumes a multifaceted and intricate function in the onset, progression, and therapeutic response of NSCLC, serving as a crucial focal point for comprehending the tumor microenvironment and formulating novel therapeutic methods. The study aims to review the biological properties and potential processes of TAM in NSCLC, investigate its involvement in the clinical of NSCLC patients, and discuss its potential as a therapeutic target.

Macrophages in the tumor microenvironment (TME) regulated gastric cancer progression, but the mechanism of macrophage polarization in gastric cancer progression remained unclear. This study mainly explored the molecular mechanism of macrophage polarization in the tumor microenvironment and its impact on the progression of gastric cancer. KPNA2 and KPNB1 expressions in cancer tissues and adjacent non-cancerous tissues were quantified via RT-qPCR and western blot. A correlation analysis was conducted between KPNA2 and KPNB1 expressions, utilizing the GEPIA2 database to link them with macrophage polarization. KPNA2-KPNB1 interaction was investigated on STRING, verified by Co-IP and IF assays. Raw246.7 cells were transfected with KPNA2 overexpression with or without si-KPNB1 plasmids. Then, M1/M2 macrophage markers and the proportion of M2 macrophages were measured by RT-qPCR, western blot, and IF. Co-culturing transfected Raw246.7 with MFC cells showed gastric cancer cell proliferation, apoptosis, migration, and invasion via CCK-8, flow cytometry, and transwell assays. KPNA2 and KPNB1 in gastric cancer tissues were elevated, exhibiting a positive correlation between them. KPNA2 overexpression facilitated the differentiation of macrophages into M2 type. KPNA2 overexpression in macrophages co-cultured with MFC cells stimulated MFC cells proliferation, repressed apoptosis, and enhanced migration/invasion. The interaction between KPNA2 and KPNB1 was confirmed through Co-IP and IF assays. Si-KPNB1 reversed the effects of KPNA2 overexpression on macrophages and gastric cancer cells. KPNA2 promoted the M2 polarization of macrophages by upregulating KPNB1, thereby inducing the proliferation and metastasis of gastric cancer.

Non-small cell lung cancer (NSCLC) is a malignant tumor with high morbidity and mortality. Ginsenosides have been shown to have strong antitumor activity, inhibiting tumor cell growth and promoting apoptosis. In this paper, the effects of ginsenoside CK on the proliferation and apoptosis of NSCLC 95D and NCI-H460 cells were investigated by CCK8, colony formation assay, flow cytometry, fluorescence staining assay, and Western Blot, and it was found that ginsenoside CK could significantly inhibit the growth and proliferation of non-small cell lung cancer, and it was also clarified that the mechanism of its action was realized by the mitochondrial apoptosis pathway. It provides new therapeutic ideas for lung cancer and other major tumor diseases.

The silent killer epithelial ovarian cancer (EOC) is a lethal malignancy with high mortality rate and often diagnosed at an advanced stage. Traditional chemotherapy for EOC remains unsatisfactory as the tumor microenvironment (TME) is complicated and contains multiple factors such as tumor associated macrophages (TAMs). Therefore, a drug delivery system which codelivery chemotherapy drug and immune modulator for EOC treatment is urgently needed.

Follicle-stimulating hormone peptide-conjugated paclitaxel and ginsenoside Rh2 codelivery liposomes (FSH@PTX-Rh2-Lips) were prepared in this study. FSH was decorated on the liposomal surface to enhance cellar uptake, PTX was used to kill cancer cells, and Rh2 was added to induce macrophages repolarization as well as a member material. The targeting, anti-tumor effect and impact on macrophage repolarization of FSH@PTX-Rh2-Lips were evaluated in vitro and in vivo.

With the ideal physicochemical properties, FSH@PTX-Rh2-Lips displayed increased cellular uptake, strong cytotoxicity to ID8 cells, inhibitory effect of tumor cell metastasis, and ability to induce macrophage repolarization from M2 to M1 in vitro. The tumor-bearing mice model suggested FSH@PTX-Rh2-Lips showed significant effect on antitumor and tumor recurrence, and the mechanism of FSH@PTX-Rh2-Lips in treatment of EOC was related to inhibiting tumor growth and inducing macrophage repolarization.

FSH@PTX-Rh2-Lips with function of affecting TAMs repolarization and altering the TME were successfully prepared and might offer an effective therapeutic strategy against EOC.

Colorectal cancer (CRC) poses a significant health burden worldwide and necessitates novel treatment approaches with fewer side effects than conventional chemotherapy. Many natural compounds have been tested as possible cancer treatments. Plants in the genus Panax have been widely studied due to their therapeutic potential for various diseases such as inflammatory disorders and cancers. Extracts from plants of genus Panax activate upstream signals, including those related to autophagy and the generation of reactive oxygen species, to induce intrinsic apoptosis in CRC cells. The root extract of Panax notoginseng (P. notoginseng) regulated the gut microbiota to enhance the T-cell-induced immune response against CRC. Protopanaxadiol (PPD)-type ginsenosides, especially Rh2, Rg3, Rb1, and Rb2, significantly reduced proliferation of CRC cells and tumor size in a xenograft mouse model, as well as targeting programmed death (PD)-1 to block the immune checkpoint of CRC cells. Moreover, modified nanocarriers with ginsenosides upregulated drug efficacy, showing that ginsenosides can also be utilized as drug carriers. An increasing body of studies has demonstrated the potential of the genus Panax in curing CRC. Ginsenosides are promising active compounds in the genus Panax, which can also support the activity of conventional cancer therapies.

The development of malignant tumors is a complex process that involves the tumor microenvironment (TME). An immunosuppressive TME presents significant challenges to current cancer therapies, serving as a key mechanism through which tumor cells evade immune detection and play a crucial role in tumor progression and metastasis. This impedes the optimal effectiveness of immunotherapeutic approaches, including cytokines, immune checkpoint inhibitors, and cancer vaccines. Tumor-associated macrophages (TAMs), a major component of tumor-infiltrating immune cells, exhibit dual functionalities: M1-like TAMs suppress tumorigenesis, while M2-like TAMs promote tumor growth and metastasis. Consequently, the development of various nanocarriers aimed at polarizing M2-like TAMs to M1-like phenotypes through distinct mechanisms has emerged as a promising therapeutic strategy to inhibit tumor immune escape and enhance antitumor responses. This Review covers the origin and types of TAMs, common pathways regulating macrophage polarization, the role of TAMs in tumor progression, and therapeutic strategies targeting TAMs, aiming to provide a comprehensive understanding and guidance for future research and clinical applications.

Breast cancer is the most prevalent cancer and the second leading cause of cancer-related mortality among women globally, resulting in considerable psychological and physical distress for patients. Our previous study synthesized a novel derivative, 2-Deoxy-Rh2, which exhibited anticancer properties by influencing glycolysis and mitochondrial respiration. The objective of the current study was to investigate the anti-proliferative effects and underlying mechanisms of 2-Deoxy-Rh2 on human breast cancer cell lines MCF-7 and MDA-MB-231. In our experiments, we observed that 2-Deoxy-Rh2 reduced cell viability and induced cell cycle arrest, reactive oxygen species accumulation, and mitochondrial dysfunction. Furthermore, treatment with 2-Deoxy-Rh2 affected autophagic flux and induction, leading to increased expression of microtubule-associated protein light chain 3B (LC3B) and decreased expression of sequestosome 1 (P62) expression in both two breast cancer cell lines, which could be reversed by 3-Methyladenine (3-MA). Additionally, the AMPK signaling pathway plays a crucial role in 2-Deoxy-Rh2-induced autophagy. 2-Deoxy-Rh2 modulated the expression levels of mTOR and AMPK in MCF-7 and MDA-MB-231 cells, resulting in the cellular homeostasis disruption, autophagy and apoptosis, which was further corroborated by compound C (CC). Finally, the study validated the antitumor activity and mechanism of 2-Deoxy-Rh2 in vivo using Balb/c mice bearing 4T1 tumor cells. Overall, the results suggest that 2-Deoxy-Rh2 can induce apoptosis and autophagic cell death through the AMPK/mTOR signaling pathway, positioning it as a promising candidate for an antitumor agent against breast cancer.

Higher and richer nutrient requirements are typical features that distinguish tumor cells from AU: cells, ensuring adequate substrates and energy sources for tumor cell proliferation and migration. Therefore, nutrient deprivation strategies based on targeted technologies can induce impaired cell viability in tumor cells, which are more sensitive than normal cells. In this review, nutrients that are required by tumor cells and related metabolic pathways are introduced, and anti-tumor strategies developed to target nutrient deprivation are described. In addition to tumor cells, the nutritional and metabolic characteristics of other cells in the tumor microenvironment (including macrophages, neutrophils, natural killer cells, T cells, and cancer-associated fibroblasts) and related new anti-tumor strategies are also summarized. In conclusion, recent advances in anti-tumor strategies targeting nutrient blockade are reviewed, and the challenges and prospects of these anti-tumor strategies are discussed, which are of theoretical significance for optimizing the clinical application of tumor nutrition deprivation strategies.

Lung cancer remains a leading cause of cancer-related deaths worldwide, necessitating innovative treatments. Tumor-associated macrophages (TAMs) are primary immunosuppressive effectors that foster tumor proliferation, angiogenesis, metastasis, and resistance to therapy. They are broadly categorized into proinflammatory M1 and tumor-promoting M2 phenotypes, with elevated M2 infiltration correlating with poor prognosis. Strategies aimed at inhibiting TAM recruitment, depleting TAMs, or reprogramming M2 to M1 are therefore highly promising. Key signaling pathways, such as CSF-1/CSF-1R, IL-4/IL-13-STAT6, TLRs, and CD47-SIRPα, regulate TAM polarization. Additionally, macrophage-based drug delivery systems permit targeted agent transport to hypoxic regions, enhancing therapy. Preclinical studies combining TAM-targeted therapies with chemotherapy or immune checkpoint inhibitors have yielded improved responses and prolonged survival. Several clinical trials have also reported benefits in previously unresponsive patients. Future work should clarify the roles of macrophage-derived exosomes, cytokines, and additional mediators in shaping the immunosuppressive tumor microenvironment. These insights will inform the design of next-generation drug carriers and optimize combination immunotherapies within precision medicine frameworks. Elucidating TAM phenotypes and their regulatory molecules remains central to developing novel strategies that curb tumor progression and ultimately improve outcomes in lung cancer. Importantly, macrophage-based immunomodulation may offer expanded treatment avenues.

Lung cancer remains a major global health challenge and one of the leading causes of cancer-related deaths worldwide. Despite significant advancements in treatment, challenges such as drug resistance, side effects, metastasis and recurrence continue to impact patient outcomes and quality of life. In response, there is growing interest in complementary and integrative approaches to cancer care. Traditional Chinese medicine (TCM), with its long history, abundant clinical experience, holistic perspective and individualized approach, has garnered increasing attention for its role in lung cancer prevention and management. This review provides a comprehensive overview of the advances in TCM for lung cancer treatment, covering its theoretical foundation, treatment principles, clinical experiences and evidence supporting its efficacy. We also provide a systematic summary of the preclinical mechanisms, through which TCM impacts lung cancer, including the induction of cell death, reversal of drug resistance, inhibition of metastasis and modulation of immune responses. Additionally, future prospects for TCM in lung cancer treatment are discussed, offering insights into its expanded application and integration with modern medicine to address this challenging disease.

Metastasis is a hallmark of advanced cancer, and the liver is a common site for secondary metastasis of many tumor cells, including colorectal, pancreatic, gastric, and prostate cancers. Macrophages in the tumor microenvironment (TME) promote tumor cell metastasis through various mechanisms, including angiogenesis and immunosuppression, and play a unique role in the development of liver metastasis. Macrophages are affected by a variety of factors. Under conditions of hypoxia and increased acidity in the TME, more factors are now found to promote the polarization of macrophages to the M2 type, including exosomes and amino acids. M2-type macrophages promote tumor cell angiogenesis through a variety of mechanisms, including the secretion of factors such as VEGF, IL-1β, and TGF-β1. M2-type macrophages are subjected to multiple regulatory mechanisms. They also interact with various cells within the tumor microenvironment to co-regulate certain conditions, including the creation of an immunosuppressive microenvironment. This interaction promotes tumor cell metastasis, drug resistance, and immune escape. Based on the advent of single-cell sequencing technology, further insights into macrophage subpopulations in the tumor microenvironment may help in exploring new therapeutic targets in the future. In this paper, we will focus on how macrophages affect the TME, how tumor cells and macrophages as well as other immune cells interact with each other, and further investigate the mechanisms involved in liver metastasis of tumor cells and their potential as therapeutic targets.

Cancer remains a formidable global health challenge, necessitating innovative therapeutic approaches to enhance treatment efficacy and reduce adverse effects. The traditional Chinese medicine (TCM), as an embodiment of ancient wisdom, has been validated to regulate the holistic human capacity against both internal and external "evils" in accordance with TCM principles. Therefore, it stands to reason to integrate TCM into current cancer therapy paradigms, such as chemotherapy, immunotherapy, and targeted therapy. This strategy conceptually intends to circumvent the inevitable side effects derived from present treatment, alleviate the discomfort, mollify the detrimental mood and synergize tumoricidal effects of distinct approaches. However, it is still vague whether TCM exert favorable function in cancer treatment. Therefore, it is imperative to retrieve and compile the existing literature on TCM in the realm of cancer, followed by a comprehensive recapitulation and synthesis of its core findings. Recently, with the advancement of contemporary biologic and medical theory and technology, it has become both feasible and imperative to elucidate the molecular signaling mechanisms and cellular biology underlying TCM. Specifically, leveraging TCM pharmaceutic components can not only directly impact tumor biology at the molecular level, but regulate the tumor immune environment through distinct pathways. Additionally, the administration of external TCM treatments such as acupuncture and moxibustion also demonstrates beneficial effects in cancer patients. Through comprehensive analysis, we demonstrated that TCM not only potentially increases the efficacy of conventional cancer treatments, but also significantly mitigates their toxic side effects, thereby prolonging patients' prognosis and improving their living quality. Furthermore, we have underscored the challenges and prospects associated with the integration of TCM into contemporary oncological practices, placing particular emphasis on the imperative for rigorous clinical trials and molecular investigations to substantiate the efficacy and safety of these combined therapeutic approaches. This synthesis aims to pave the way for a more integrated approach to cancer treatment rooted in both traditional wisdom and cutting-edge science.

Triple-Negative Breast Cancer (TNBC), the most challenging subtype of Breast Cancer (BC), currently lacks targeted therapy, presenting a significant therapeutic gap in its management. Tumor Associated Macrophages (TAMs) play a significant role in TNBC progression and could be targeted by repolarizing them from M2 to M1 phenotype. Matairesinol (MAT), a plant lignan, has been shown to exhibit anticancer, anti-inflammatory and immunomodulatory activities. In this study, we explored how MAT-induced repolarization of THP-1-derived M2 macrophages towards the M1 phenotype, which could effectively target the TNBC cell line, MDA-MB-231.

The differential expression of genes in THP-1-derived macrophages at mRNA levels was evaluated by RNAseq assay. An inverted microscope equipped with a CMOS camera was utilized to capture the morphological variations in THP-1 cells and THP-1-derived macrophages. Relative mRNA expression of M1 and M2 specific marker genes was quantified by qRT-PCR. Cell viability and induction of apoptosis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1 dye) assays, respectively.

MAT reduced the viability of M2a and M2d macrophages and repolarized them to M1 phenotype. Conditioned medium (CM) from MAT-treated M2a and M2d macrophages significantly reduced the viability of TNBC cells by apoptosis.

Targeting M2 macrophages is an important strategy to regulate cancer progression. Our study provides evidence that MAT may be a promising drug candidate for developing novel anti-TNBC therapy. However, further studies are warranted to thoroughly elucidate the molecular mechanism of action of MAT and evaluate its therapeutic potential in TNBC in vitro and in vivo models.

Ginsenoside Rh2 (G-Rh2) is a vital bioactive compound in Traditional Chinese Medicine, celebrated for its strong pharmacological properties, particularly its potent antitumor effects. However, its poor water solubility and limited bioavailability have necessitated the development of a novel drug delivery method. In this study, we utilized an indocyanine green carboxylic acid-hydroxypropyl cellulose-abietic acid-bovine serum albumin hydrogel (ICG-HPC-AA/BSA hydrogel) as a tumor in situ vaccine to enhance the permeability, retention, and tumor-targeted therapeutic efficacy of G-Rh2. We examined the therapeutic impact of a G-Rh2-loaded hydrogel combined with systemic PD-1 antibody treatment in murine models of H22 liver cancer and CT26 colon cancer. Additionally, we explored the immune microenvironment of the tumors influenced by this in situ vaccination strategy.

Chronic inflammation is closely related to the occurrence and progression of many cancers, especially colorectal cancer (CRC), which can be triggered by repeated and sustained induction of colitis in mice. CRC is a typical type of cancer that can be caused by inflammation and NLRP3 inflammasome dysregulation plays a certain role in the pathogenesis of CRC.

As an edible Chinese medicine, Abrus cantoniensis Hance (ACH) has both anti-inflammatory and anti-tumor activities. However, most research has focused on inflammation-related diseases, and less research has been done on its active ingredients and targets and its application in CRC. Here, this study deeply explored the target of 2',4'-DHC and its pharmacological mechanism in anti-colon cancer, and provided a new strategy for its drug development and treatment of colon cancer.

The cytotoxicity of ACH's active ingredient in HT29 and CT26 cells was measured by CCK-8, clone formation, apoptosis, and cell cycle assay. The metastasis inhibition of CRC cells was determined by wound-healing assay. Western blotting was used to detect the NLRP3 inflammasome activation, pyroptosis, and apoptosis activation. Finally, the in vivo efficacy of 2',4'-DHC was verified by establishing CT26 and HT29 tumor transplant models in mice.

Here, our study firstly demonstrated that 2',4'-DHC inhibited the growth of CRC cells mainly by increasing CRC cell death and ameliorating tumor immunosuppressive environment, which is verified by inducing apoptosis and pyroptosis by regulating caspase-3/4/11, arresting cell cycle in G2/M phase, suppressing the migration of CRC cells, and inhibiting NLRP3 inflammasome activation through inhibiting the NF-κB pathway, enhancing the anticancer immune response by increasing the infiltration of T cells and function of CD8+ cytotoxic T cells but decreasing the infiltration of CD11b+ CD206+ macrophages and function. Importantly, the administration of 2',4'-DHC decreased liver and spleen indexs to mice's normal levels and reduced the burden of CT26 and HT29 tumor-bearing in mice without pathological changes in the major organs.

2',4'-DHC inhibited CRC growth through various mechanisms, mainly by regulating NLRP3 inflammasome and caspase-3/4/11 activation. Considering the anti-tumor and immunomodulation roles of 2',4'-DHC, it might be a new direction for the development of new strategies to treat colorectal cancer.

As an important innate immune cell in the body, macrophages have a strong ability to phagocytic tumor cells and maintain the innate immune response. Tumor-associated macrophages play a more prominent role in regulating tumor immunity and are currently an important target of antitumor immunity. As a new type of antitumor therapy, tumor immunotherapy has great potential, combined chemotherapy, targeting and other therapeutic means can significantly enhance the antitumor therapy effect. At present, a number of natural products have been proved to have significant immunomodulatory and antitumor effects, and have become a hot field of antitumor immunity research. Studies have found that a variety of natural products, such as polysaccharides, flavonoids, saponins, lactones, and alkaloids, can induce the polarization of M1 macrophages, inhibit the polarization of M2 macrophages, and regulate the expression of immune-related cytokines by targeting specific signaling pathways to enhance the killing effect of macrophages on tumor cells and improve the tumor immune microenvironment, and finally better play the antitumor immune function. In this paper, by summarizing the research results of the specific mechanism of natural products targeting tumor-associated macrophages to exert antitumor immunity in recent years, we discussed the aspects of natural products targeting tumor-associated macrophages to enhance antitumor immunity, in order to provide a new research idea for tumor immunotherapy and further improve the effectiveness of clinical antitumor therapy.

Regulatory immune cells regulate immune responses through various mechanisms, affecting the occurrence, development, and therapeutic effects of tumors. In this article, we reviewed the important roles of regulatory immune cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), myeloid-derived suppressor cells (MDSCs), regulatory dendritic cells (DCregs), and tumor-associated macrophages (TAMs), in the tumor microenvironment (TME). The immunomodulatory effects of natural products, such as polysaccharides, polyphenols, glycosides, alkaloids, terpenoids, quinones, and other compounds, which affect the functions of regulatory immune cells through molecular signaling pathways, thereby enhancing the potential of the antitumor immune response, are discussed. These findings provide new ideas and possibilities for the application of natural products in tumor treatment, which can help enhance the effectiveness of tumor treatment and improve patient prognosis.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies globally, posing a major challenge to global health care. Protopanaxadiol ginsenosides (PDs) have been believed to significantly improve liver diseases. PDs, such as Rg3, have been developed as a new class of anti-cancer drugs. Ginsenosides Rb1, Rd, Rg3, and Rh2 exhibit effective anti-inflammatory and anti-tumor activities. Studies have confirmed that PDs could be used to treat HCC. However, the mechanism of action of PDs on HCC remains unclear. In the study, we reviewed the anti-HCC effects and mechanisms of PDs including Rb1, Rd, Rg3, Rg5, Rh2, Rk1, and Compound K (CK). Then, we searched for relevant targets of PDs and HCC from databases and enriched them for analysis. Subsequently, molecular docking was simulated to reveal molecular mechanisms. We found that PDs may treat HCC through multiple signaling pathways and related targets. PDs could inhibit the proliferation, invasion, and metastasis of HCC while promoting apoptosis and inducing differentiation. In conclusion, this review and network pharmacological analysis might offer a direction for in-depth research on related mechanisms. These insights will aid in the direction of further pharmacological studies and the development of safe and effective clinical drugs.

Endometriosis (EMS) is defined as the appearance, growth, infiltration, and repeated bleeding of endometrioid tissue (glands and stroma) outside the uterus cavity, which can form nodules and masses. Endometriosis is a chronic inflammatory estrogen-dependent disease and occurs in women of reproductive age. This disorder may significantly affect the quality of life of patients. The pathogenic processes involved in the development and maintenance of endometriosis remain unclear. Current treatment options for endometriosis mainly include drug therapy and surgery. Drug therapy mainly ties to the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal drugs. However, these drugs may produce adverse effects when used for long-term treatment of endometriosis, such as nausea, vomiting gastrointestinal reactions, abnormal liver and kidney function, gastric ulcers, and thrombosis. Although endometriosis lesions can be surgically removed, the disease has a high recurrence rate after surgical resection, with a recurrence rate of 21.5% within 2 years and 40% to 50% within 5 years. Thus, there is an urgent need to develop alternative or additional therapies for the treatment of endometriosis. In this review, we give a systematic summary of therapeutic multiple component prescriptions (including traditional Chinese medicine and so on), bioactive crude extracts of plants/herbs and purified compounds and their newly found mechanisms reported in literature in recent years against endometriosis.

Ginseng, the dried root of Panax ginseng C.A. Mey., is widely used in Chinese herbal medicine. Ginsenosides, the primary active components of ginseng, exhibit diverse anticancer functions through various mechanisms, such as inhibiting tumor cell proliferation, promoting apoptosis, and suppressing cell invasion and migration. In this article, the mechanism of action of 20 ginsenoside subtypes in tumor therapy and the research progress of multifunctional nanosystems are reviewed, in order to provide reference for clinical prevention and treatment of cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide, with metastasis being the primary cause of mortality in lung cancer patients, and its prevention and control efficacy remain limited. In recent years, immunotherapy has emerged as a promising direction for overcoming the bottleneck of metastasis. Macrophages, as essential components of innate immunity, participate in the entire process of tumor initiation and progression. Tumor-associated macrophages (TAMs) represent the most abundant immune population in the tumor microenvironment (TME), displaying both anti-tumor M1-like and pro-tumor M2-like phenotypes. The latter promotes tumor invasion and metastasis, angiogenesis, lymphangiogenesis, immune suppression, and reactivation of dormant disseminated tumor cells (DTCs), thereby facilitating tumor metastasis. In recent years, traditional Chinese medicine (TCM) has shown significant efficacy in inhibiting tumor metastasis and has been extensively validated. It exerts anti-tumor effects by reducing the recruitment of TAMs, inhibiting M2-like polarization, and modulating cytokines and proteins in the TME. This paper reviews the relationship between TAMs and lung cancer metastasis, elucidates the targets and mechanisms of TCM in regulating TAMs to prevent and treat lung cancer metastasis, aiming to provide insights into lung cancer prevention and treatment.
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Non-small cell lung cancer (NSCLC) presents a complex and diverse disease, exhibiting variations at individuals' cellular and histological levels. This complexity gives rise to different subtypes and genetic mutations, posing challenges for accurate diagnosis and effective treatment. Nevertheless, continuous progress in medical research and therapies is continually shaping the landscape of NSCLC diagnosis and management. The treatment of NSCLC has undergone significant advancements in recent years, especially with the emergence of targeted therapies that have shown remarkable efficacy in patients with actionable mutations. This has ushered in the era of personalized medicine in NSCLC treatment, with improvements in molecular and immunohistochemical techniques contributing to enhanced progression-free survival. This review focuses on the latest progress, challenges, and future directions in developing targeted therapies for NSCLC, including tyrosine kinase inhibitors (TKIs), DNA-damaging agents, immunotherapy regimens, natural drug therapy, and nanobodies. Furthermore, recent randomized studies have demonstrated enhanced overall survival in patients receiving different targeted and natural drug therapies.

Recent research has demonstrated the immunomodulatory potential of Panax notoginseng in the treatment of chronic inflammatory diseases and cerebral hemorrhage, suggesting its significance in clinical practice. Nevertheless, the complex immune activity of various components has hindered a comprehensive understanding of the immune-regulating properties of Panax notoginseng, impeding its broader utilization. This review evaluates the effect of Panax notoginseng to various types of white blood cells, elucidates the underlying mechanisms, and compares the immunomodulatory effects of different Panax notoginseng active fractions, aiming to provide the theory basis for future immunomodulatory investigation.

The tumor microenvironment (TME) can aid tumor cells in evading surveillance and clearance by immune cells, creating an internal environment conducive to tumor cell growth. Consequently, there is a growing focus on researching anti-tumor immunity through the regulation of immune cells within the TME. Various bioactive compounds in traditional Chinese medicine (TCM) are known to alter the immune balance by modulating the activity of immune cells in the TME. In turn, this enhances the body's immune response, thus promoting the effective elimination of tumor cells. This study aims to consolidate recent findings on the regulatory effects of bioactive compounds from TCM on immune cells within the TME. The bioactive compounds of TCM regulate the TME by modulating macrophages, dendritic cells, natural killer cells and T lymphocytes and their immune checkpoints. TCM has a long history of having been used in clinical practice in China. Chinese medicine contains various chemical constituents, including alkaloids, polysaccharides, saponins and flavonoids. These components activate various immune cells, thereby improving systemic functions and maintaining overall health. In this review, recent progress in relation to bioactive compounds derived from TCM will be covered, including TCM alkaloids, polysaccharides, saponins and flavonoids. This study provides a basis for further in-depth research and development in the field of anti-tumor immunomodulation using bioactive compounds from TCM.

Ginsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function.

We examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR.

Treatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor's aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier.

G-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes.

Pulmonary premetastatic niche (PMN) formation plays a key role in the lung metastasis of hepatocellular carcinoma (HCC). Hypoxia promotes the secretion of tumor-derived exosomes (TDEs) and facilitates the formation of PMN. However, the mechanisms remain unexplored.

TDEs from normoxic (N-TDEs) or hypoxic (H-TDEs) HCC cells were used to induce fibroblast activation in vitro and PMN formation in vivo. Oleanolic acid (OA) was intragastrically administered to TDEs-preconditioned mice. Bioinformatics analysis and drug affinity responsive target stability (DARTS) assays were performed to identify targets of OA in fibroblasts.

H-TDEs induced activation of pulmonary fibroblasts, promoted formation of pulmonary PMN and subsequently facilitated lung metastasis of HCC. OA inhibited TDEs-induced PMN formation and lung metastasis and suppressed TDEs-mediated fibroblast activation. MAPK1 and MAPK3 (ERK1/2) were the potential targets of OA. Furthermore, H-TDEs enhanced ERK1/2 phosphorylation in fibroblasts in vitro and in vivo, which was suppressed by OA treatment. Blocking ERK1/2 signaling with its inhibitor abated H-TDEs-induced activation of fibroblasts and PMN formation. H-TDEs-induced phosphorylation of ERK1/2 in fibroblasts touched off the activation NF-κB p65, which was mitigated by OA. In addition, the ERK activator C16-PAF recovered the activation of ERK1/2 and NF-κB p65 in H-TDEs-stimulated MRC5 cells upon OA treatment.

The present study offers insights into the prevention of TDEs-induced PMN, which has been insufficiently investigated. OA suppresses the activation of inflammatory fibroblasts and the development of pulmonary PMN by targeting ERK1/2 and thereby has therapeutic potential in the prevention of lung metastasis of HCC.

Cancer immunotherapy has garnered promise in tumor progression, invasion, and metastasis through establishing durable and memorable immunological activity. However, low response rates, adverse side effects, and high costs compromise the additional benefits for patients treated with current chemical and biological agents. Chinese herbal medicines (CHMs) are a potential treasure trove of natural medicines and are gaining momentum in cancer immunomodulation with multi-component, multi-target, and multi-pathway characteristics. The active ingredient extracted from CHMs benefit generalized patients through modulating immune response mechanisms. Additionally, the introduction of nanotechnology has greatly improved the pharmacological qualities of active ingredients through increasing the hydrophilicity, stability, permeability, and targeting characteristics, further enhancing anti-cancer immunity. In this review, we summarize the mechanism of active ingredients for cancer immunomodulation, highlight nano-formulated deliveries of active ingredients for cancer immunotherapy, and provide insights into the future applications in the emerging field of nano-formulated active ingredients of CHMs.

Patients diagnosed with non-small cell lung cancer (NSCLC) have a limited lifespan and exhibit poor immunotherapy outcomes. M1 macrophages have been found to be essential for antitumor immunity. This study aims to develop an immunotherapy response evaluation model for NSCLC patients based on transcription. RNA sequencing profiles of 254 advanced-stage NSCLC patients treated with immunotherapy are downloaded from the POPLAR and OAK projects. Immune cell infiltration in NSCLC patients is examined, and thereafter, different coexpressed genes are identified. Next, the impact of M1 macrophage-related genes on the prognosis of NSCLC patients is investigated. Six M1 macrophage coexpressed genes, namely, NKX2-1, CD8A , SFTA3, IL2RB, IDO1, and CXCL9, exhibit a strong association with the prognosis of NSCLC and serve as effective predictors for immunotherapy response. A response model is constructed using a Cox regression model and Lasso Cox regression analysis. The M1 genes are validated in our TD-FOREKNOW NSCLC clinical trial by RT-qPCR. The response model shows excellent immunotherapy response prediction and prognosis evaluation value in advanced-stage NSCLC. This model can effectively predict advanced NSCLC prognosis and aid in identifying patients who could benefit from customized immunotherapy as well as sensitive drugs.

Shuangshen granules (SSG), a nationally patented Chinese medicinal formula, including Panax quinquefolium L., Panax notoginseng (Burkill) F. H. Chen, and Cordyceps sinensis (Berk.) Sacc., has demonstrated remarkable therapeutic effects on pancreatic cancer in clinical treatment for nearly 10 years. Previous pharmacological researches have found that its main components, including ginsenosides and cordycepin have anticancer or preventive effects on pancreatic ductal adenocarcinoma (PDAC), which may be associated with immune metabolism. However, the underlying pharmacological mechanism of SSG in the truncation effect of PDAC progression is still unclear.

To comprehensively understand the infiltrating immune cells during the different stages of the PDAC development chain and search for immune-related biomarkers that could potentially serve as drug targets through bioinformatic analysis. Meanwhile, the truncation effect of SSG on PDAC progression was also investigated.

The gene expression profiles at different PDAC developmental stages, including normal pancreas, pancreatic intraepithelial neoplasia (PanIN), and PDAC, were retrieved from the GEO database. The GEO2R tool was used to identify differentially expressed genes among the three groups. Functional enrichment analysis was performed with the GSEA software and Metascape platform. The CIBERSORT algorithm evaluated immune cell infiltration in the three groups, and immune-related biomarkers were identified. Correlation analysis was employed to examine the association between immune cells and the biomarkers. One of these biomarkers was selected for immunohistochemistry validation in human samples. Lastly, the effectiveness of SSG against PDAC progression and the influence on the selected biomarker were validated in vivo. The underlying pharmacological mechanisms were also explored.

One dataset was obtained, where the functional enrichment of DEGs primarily involved immune effector processes and cytokine production of immune cells. The differential immune cells reflected during the progression from PanIN to PDAC were B memory cells, monocytes, M2 macrophages, and activated dendritic cells. The upregulation of ACTA2 was closely associated with M2 macrophage regulation. The immunohistochemistry on human samples validated significant differences in ACTA2 expression levels as the PDAC progressed. Moreover, animal experiments revealed that the national patented drug SSG ameliorated the pathological changes, decreased the expression of ACTA2 and its functional protein α-smooth muscle actin during PDAC progression. The underlying pharmacological mechanism was related to the regulation of macrophage polarization and downregulation of TGF-β/Smad signaling pathway.

The immunosuppressive environment changes during the PDAC progression. ACTA2 is a potential immuned-target for drug prevention of PDAC, while SSG could be a promising drug candidate.

Tumour-associated macrophages (TAMs), particularly M2-TAMs, constitute the largest proportion of immune cells in the solid tumour microenvironment, playing a crucial role in tumour progression and correlating with poor prognosis. TAMs promote the proliferation, invasion, and metastasis of tumour cells by remodelling the extracellular matrix, inhibiting immunity, promoting immune escape and tumour angiogenesis, and affecting cell metabolism. Traditional Chinese medicine (TCM) has been used clinically in China for millennia. Chinese herbs exhibit potent antitumour effects with minimal to no toxicity, substantially contributing to prolonging the lives of patients with cancer and improving their quality of life. TCM has unique advantages in improving the solid tumour microenvironment, particularly in regulating TAMs to further inhibit tumour angiogenesis, reduce drug resistance, reverse immunosuppression, and enhance antitumour immunity. This review highlights the TAM-associated mechanisms within the solid tumour microenvironment, outlines the recent advancements in TCM targeting TAMs for antitumour effects, emphasises the superiority of combining TCM with standard treatments or new nano-drug delivery systems, and evaluates the safety and efficacy of TCM combined with conventional treatments via clinical trials to provide insights and strategies for future research and clinical treatment.

Single-cell RNA sequencing (scRNA-seq) is an emerging technology used for cellular transcriptome analysis. The application of scRNA-seq has led to profoundly advanced oncology research, continuously optimizing novel therapeutic strategies. Intratumor heterogeneity extensively consists of all tumor components, contributing to different tumor behaviors and treatment responses. Tumor-associated macrophages (TAMs), the core immune cells linking innate and adaptive immunity, play significant roles in tumor progression and resistance to therapies. Moreover, dynamic changes occur in TAM phenotypes and functions subject to the regulation of the tumor microenvironment. The heterogeneity of TAMs corresponding to the state of the tumor microenvironment has been comprehensively recognized using scRNA-seq. Herein, we reviewed recent research and summarized variations in TAM phenotypes and functions from a developmental perspective to better understand the significance of TAMs in the tumor microenvironment.

The field of personalized medicine has gained increasing attention in cancer care, with the aim of tailoring treatment strategies to individual patients for improved outcomes. Herbal medicine, with its long-standing historical use and extensive bioactive compounds, offers a rich source of potential treatments for various diseases, including cancer.

To provide an overview of the current knowledge and evidence associated with incorporating herbal compounds into precision medicine strategies for cancer diseases. Additionally, to explore the general characteristics of the studies included in the analysis, focusing on their key features and trends.

A comprehensive literature search was conducted from multiple online databases, including PubMed, Scopus, Web of Science, and CINAHL-EBSCO. The search strategy was designed to identify studies related to personalized cancer medicine and herbal interventions.

Publications pertaining to cancer research conducted through in vitro, in vivo, and clinical studies, employing natural products were included in this review.

Two review authors independently applied inclusion and inclusion criteria, data extraction, and assessments of methodological quality. The quality assessment and biases of the studies were evaluated based on modified Jadad scales. A detailed quantitative summary of the included studies is presented, providing a comprehensive description of their key features and findings.

A total of 121 studies were included in this review for analysis. Some of them were considered as comprehensive experimental investigations both in vitro and in vivo. The majority (n = 85) of the studies included in this review were conducted in vitro, with 44 of them specifically investigating the effects of herbal medicine on animal models. Additionally, 7 articles with a combined sample size of 31,271 patients, examined the impact of herbal medicine in clinical settings.

Personalized medication can optimize the use of herbal medicine in cancer treatment by considering individual patient factors such as genetics, medical history, and other treatments. Additionally, active phytochemicals found in herbs have shown potential for inhibiting cancer cell growth and inducing apoptosis, making them a promising area of research in preclinical and clinical investigations. Please cite this article as: Tayeb BA, Kusuma IY, Osman AAM, Minorics R. Herbal compounds as promising therapeutic agents in precision medicine strategies for cancer: A systematic review. J Integr Med. 2024; 22(2): 137-162.

This study is aim to discern the Traditional Chinese Medicine (TCM) syndrome classifications relevant to immunotherapy sensitive in non-small cell lung cancer (NSCLC) patients, and to delineate intestinal microbiota biomarkers and impact that wield influence over the efficacy of NSCLC immunotherapy, grounded in the TCM theory of "lung and large intestine stand in exterior-interior relationship."

The study cohort consisted of patients with advanced NSCLC who received treatment at the Oncology Department of Chengdu Fifth People's Hospital. These patients were categorized into distinct TCM syndrome types and subsequently administered immune checkpoint inhibitors (ICIs), specifically PD-1 inhibitors. Stool specimens were collected from patients both prior to and following treatment. To scrutinize the differences in microbial gene sequences and species of the intestinal microbiota, 16S rRNA amplicon sequencing technology was employed. Additionally, peripheral blood samples were collected, and the analysis encompassed the assessment of T lymphocyte subsets and myeloid suppressor cell subsets via flow cytometry. Subsequently, alterations in the immune microenvironment pre- and post-treatment were thoroughly analyzed.

The predominant clinical manifestations of advanced NSCLC patients encompassed spleen-lung Qi deficiency syndrome and Qi-Yin deficiency syndrome. Notably, the latter exhibited enhanced responsiveness to ICIs with a discernible amelioration of the immune microenvironment. Following ICIs treatment, significant variations in microbial abundance were identified among the three strains: Clostridia, Lachnospiraceae, and Lachnospirales, with a mutual dependency relationship. In the subset of patients manifesting positive PD-L1 expression and enduring therapeutic benefits, the study recorded marked increases in the ratios of CD3+%, CD4+%, and CD4+/CD8+ within the T lymphocyte subsets. Conversely, reductions were observed in the ratios of CD8%, Treg/CD4+, M-MDSC/MDSC, and G-MDSC/MDSC.

The strains Clostridia, Lachnospiraceae, and Lachnospirales emerge as potential biomarkers denoting the composition of the intestinal microbiota in the NSCLC therapy. The immunotherapy efficacy of ICIs markedly accentuates in patients displaying durable treatment benefits and those expressing positive PD-L1.

This study aimed to explore the interaction between the tumor-associated macrophage (TAM) and enhancer of zeste homolog 2 (EZH2) in tumor microenvironment of lung cancer are obscure. M2 type of TAM was induced by interleukin-4 (IL-4) and interleukin-13 (IL-13) in RAW264.7 cells. Subsequently, the co-culture system of the M2 RAW264.7 treating LLC-1 cells were constructed to evaluate the cell proliferation, migration and invasion abilities. On top of that, the M2 RAW264.7 was injected into the LLC-1 cells-bearing mice. Tumor growth and the number of metastatic nodes were observed. Moreover, DNA methylation, EZH2 expression, target genes of EZH2 and the M2 type TAM-related markers were detected in vivo and in vitro . Further experiments of EZH2 function in lung cancer were carried out by the addition of EZH2 inhibitor (GSK126) and si-EZH2. M2 type of TAM was induced with IL-4 and IL-13 with increased expression of CD206, CD68, CD163 and Arg1. Following co-culture with M2 type TAM, the proliferative, invasive, migrative abilities, tumor growth and metastasis, and the DNA methylation, EZH2 level were strengthened whereas the target genes of EZH2, including p21, CDKN2A, CDKN2B were reduced in LLC-1 cells and LLC-1 cell-bearing mice. Of note, GSK126 and si-EZH2 offset the M2 type TAM's effects, and inhibited the LLC-1 cell metastasis, DNA methylation and tumor growth. M2 type TAM promoted DNA methylation in LLC-1 cells and LLC-1 cell-bearing mice, which is related to the intensified EZH2.

Lung cancer is one of the more common malignant tumors posing a great threat to human life, and it is very urgent to find safe and effective therapeutic drugs. The antitumor effect of ginsenosides has been reported to be a treatment with a strong effect and a high safety profile.

This paper aimed to investigate the inhibitory effect of ginsenoside Rb1 on 95D and NCI-H460 lung cancer cells and its pathway to promote apoptosis.

We performed the CCK-8 assay, fluorescence staining assay, flow cytometry, scratch healing assay, and Transwell assay to detect the effects of different concentrations of ginsenoside Rb1 on the antitumor activity of 95D and NCI-H460 cells and Western Blot detected the mechanism of antitumor effect.

Ginsenoside Rb1 treatment significantly increased the inhibition and apoptosis rates of 95D and NCIH460 cells and inhibited the cell cycle transition from S phase to G2/M. Rb1 induces apoptosis by altering the levels of P53, Bax, Cyto-c, Caspase-8, Caspase-3, Cleaved Caspase-3, Bcl-2, MMP-2, and MMP-9 proteins and activating the external apoptotic pathway.

Ginsenoside Rb1 inhibits proliferation and migration and induces apoptosis of 95D and NCI-H460 lung cancer cells by regulating the mitochondrial apoptotic pathway to achieve antitumor activity.