Targeted therapy for gastrointestinal stromal tumors: current status and future perspectives

• Published in: Cancer and metastasis reviews Vol. 29; no. 1; pp. 151 - 170
• Main Authors: Papaetis, Georgios S., Syrigos, Kostas N.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2010; Springer; Springer Nature B.V
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - therapeutic use; Benzamides; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Care and treatment; Cell surface; Cellular signal transduction; Chemotherapy; Clinical Trials as Topic - methods; Development and progression; Drug Delivery Systems - methods; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal cancer; Gastrointestinal Stromal Tumors - diagnosis; Gastrointestinal Stromal Tumors - drug therapy; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal system; Gastrointestinal tract; Genetic aspects; Genotypes; Growth factors; Health aspects; Humans; Imatinib; Imatinib Mesylate; Medical Oncology - trends; Medical prognosis; Medical sciences; Mesenchyme; Metastases; Metastasis; Non-Thematic Review; Oncology; Patients; Phenotypes; Piperazines - therapeutic use; Platelet-derived growth factor; Platelet-derived growth factor receptors; Prognosis; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - therapeutic use; Radiation therapy; Signal transduction; Stem cells; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Gastrointestinal stromal tumors; Imatinib; PDGFR-α; KIT; Antineoplastic agent; Platelet derived growth factor receptor A; Enzyme; Tyrosine kinase inhibitor; Targeted therapy; Transferases; Enzyme inhibitor; Gastrointestinal stromal tumor; Cancerology; Treatment; C-Onc gene; Digestive diseases; Intestinal disease; Protein-tyrosine kinase; Protooncogene
• ISSN: 0167-7659; 1573-7233
• DOI: 10.1007/s10555-010-9206-7

Gastrointestinal stromal tumors (GISTs) present 80% of gastrointestinal tract mesenchymal tumors, with systemic chemotherapy and radiotherapy being unable to improve survival of patients with advanced disease. The identification of activating mutations in either KIT cell surface growth factor receptor or platelet-derived growth factor receptor alpha, which lead to ligand-independent signal transduction, paved the way for the development of novel agents that selectively inhibit key molecular events in disease pathogenesis. The development of imatinib mesylate in the treatment of metastatic GIST represents a therapeutic breakthrough in molecularly targeted strategies, which crucially improved patients’ prognosis while its usefulness in adjuvant and neoadjuvant setting is under study. Sunitinib malate is available in the second-line setting, with ongoing studies evaluating its role in an earlier disease stage, while other targets are under intense investigation in order to enrich the therapeutical armamentarium for this disease. GIST phenotype seems to be an essential indicator of treatment response; thus, obtaining genotype information of each patient may be critical in order to tailor individualized treatment strategies and achieve maximal therapeutic results.