Recent advances in the treatment of gastrointestinal stromal tumors

Abstract

Constitutively activating mutations in the KIT and platelet-derived growth factor receptor α (PDGFRA) RTKs play a crucial role in the biology of gastrointestinal stromal tumors (GISTs), and this disease has served as an effective model for targeting gain-of-function kinase mutations in cancer. Imatinib has entered the clinical arena in the last decade and substantially improved the outcome in these formerly untreatable cancers. However, most advanced GISTs responding to imatinib progress within 2-3 years due to heterogeneous subclones harboring a range of imatinib-resistant secondary KIT mutations. Sunitinib, and more recently, regorafenib, have obtained US Food and Drug Administration approval for the treatment of GISTs after imatinib failure, and thus expanded the treatment options in resistant disease. Within this framework, we present an evaluation of current GIST management, emphasizing the most recent advances in the field together with a discussion on future steps to be taken in refractory disease.

Gastroduodenal intussusception due to gastrointestinal stromal tumor

“…Gastroduodenal intussusception (10%)1, 2 causing acute gastric outlet obstruction due to pedunculated gastric gastrointestinal stromal tumor (GIST) is rare. GIST (mesenchymal tumor) is pathologically defined by positive immunostaining for c‐kit proto‐oncogene—CD117 (95%) and CD34 (60%‐70%) 2.…”

“…GIST (mesenchymal tumor) is pathologically defined by positive immunostaining for c‐kit proto‐oncogene—CD117 (95%) and CD34 (60%‐70%) 2. Ulceration of the apical mucosa results in bleeding (50%) 2.…”

“…Treatment for localized GIST is complete surgical resection. Fletcher's risk stratification indices include tumor size, mitotic index, nonradical resection (R1), and tumor rupture 1, 2. Postoperative chemotherapy improves relapse‐free survival, but overall survival remains unchanged.…”

An innovative procedure of laparoscope combined with endoscopy for gastrointestinal stromal tumor resection and cholecystectomy: A case report and literature review

“…GISTs are rare, non-epithelial mesenchymal tumors with a potential for malignant transformation, accounting for <3% of all gastrointestinal neoplasms (27), and the most common sites of occurrence is the stomach (40-60%) (28). Despite the development of a new chemotherapeutic agent, imatinib mesylate (29), surgical resection remains the primary alternative treatment for primary GISTs (30).…”

Are Rogerofenib and Nilotinib Effective for Advanced Gastrointestinal Stromal Tumor (GIST) Patients who have Already been Given Main Treatments?

“…Regorafenib inhibits VEGFR-1,2,3, PDGFRB, FGFR1, KIT, RET and BRAF. Nilotinib inhibits ARG, KIT, PDGFRA and PDGFRB (Serrano and George, 2014). All tyrosine kinase inhibitors which are used for GISTs, have partly different targets so, a non-responder patient with a certain agent may become "responder" with another.…”