TITLE:
Gastrointestinal Stromal Tumors in the 21st Century
AUTHORS:
Rani Kanthan, Jenna-Lynn Senger, Shahid Ahmed, Selliah Chandra Kanthan
KEYWORDS:
Gastrointestinal Stromal Tumor, Targeted Therapy, Drug Resistance, Histopathology, Surgery
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.8,
July
17,
2014
ABSTRACT:
Gastrointestinal stromal
tumours (GISTs) are rare mesenchymal lesions accounting for only 0.2% of all
gastrointestinal neoplasms. These tumors arise from the interstitial cells of
Cajal, with mutations described in proto-oncogenes such as KIT, PDGFRA, DOG-1,
and SDH. The majority of these lesions are asymptomatic, thus the true
incidence remains unknown. While patients typically undergo initial endoscopy,
CT scan and/or MRI, findings are often nonspecific and require a biopsy to
identify the tumor. As such, immunohistochemical evaluation is the
gold-standard for the accurate diagnosis of GIST. Though surgical excision
remains the gold-standard for curative management, the discovery of imatinib, a
tyrosine kinase inhibitor (TKI), has revolutionized the treatment of GIST in
the 21stcentury as a
“prototype” of molecular targeted therapy for solid tumors. Risk assessment for
recurrence divides these tumors into low and high-risk categories. In the
latter, a role for adjuvant therapy with TKI confers a significantly better
prognosis than previously observed. However, secondary mutations conferring
drug resistance remain an ongoing challenge for management, as few alternative
treatment options are available for patients intolerant/refractory to TKI
therapy. In this review, we summarize the epidemiology, molecular pathogenesis,
clinical presentation, diagnosis, pathology features, management options, and
prognostic features of GISTs.