Jakhetiya A, Garg PK, Prakash G, Sharma J, Pandey R, Pandey D. Targeted therapy of gastrointestinal stromal tumours. World J Gastrointest Surg 2016; 8(5): 345-352 [PMID: 27231512 DOI: 10.4240/wjgs.v8.i5.345]
Corresponding Author of This Article
Dr. Pankaj Kumar Garg, Associate Professor, Department of Surgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, University of Delhi, Dilshad Garden, Delhi 110095, India. dr.pankajgarg@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Therapeutics Advances
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Ashish Jakhetiya, Pankaj Kumar Garg, Jyoti Sharma, Durgatosh Pandey, Department of Surgical Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India
Pankaj Kumar Garg, Department of Surgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, University of Delhi, Delhi 110095, India
Gaurav Prakash, Clinical Hematology and Bone Marrow Transplant Unit, Department of Internal Medicine, Post-Graduate Institute of Medical Education and Research, Chandigarh 160012, India
Rambha Pandey, Department of Radiation Oncology, Dr BRA Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India
Author contributions: Jakhetiya A and Garg PK searched the literature, analyzed the retrieved literature, and wrote the initial draft; Garg PK conceptualized the study; Pandey D, Prakash G and Sharma J provided critical inputs in literature search and analysis, and drafted the manuscript; all the authors read and approved the final draft.
Conflict-of-interest statement: There is no conflict of interest associated with any of the authors.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Pankaj Kumar Garg, Associate Professor, Department of Surgery, University College of Medical Sciences and Guru Teg Bahadur Hospital, University of Delhi, Dilshad Garden, Delhi 110095, India. dr.pankajgarg@gmail.com
Telephone: +91-1122-592536 Fax: +91-1122-590495
Received: September 29, 2015 Peer-review started: October 2, 2015 First decision: November 4, 2015 Revised: January 7, 2016 Accepted: March 7, 2016 Article in press: March 9, 2016 Published online: May 27, 2016 Processing time: 231 Days and 3.9 Hours
Abstract
Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majority of the tumours stain positively for the CD-117 (KIT) and discovered on GIST-1 (DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy (tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs.
Core tip: Gastrointestinal stromal tumors (GISTs) are common mesenchymal tumours of the gastrointestinal tract. They are characterized by the presence of a driver kinase-activating mutation in either CD-117 or platelet-derived growth factor receptor α. Development of tyrosine kinase inhibitors has led to a paradigm shift in the management of GISTs. Surgery is the primary modality of treatment in localized non-metastatic GISTs. Adjuvant Imatinib for three years is a preferred option for high-risk patients to lessen disease recurrence. The role of neoadjuvant Imatinib is evolving. Imatinib, Sunitinib, and Regorafinib are recommended as first, second and third-line targeted therapies, respectively, for the management of metastatic GISTs.