Emergence of imatinib resistance associated with downregulation of c-kit expression in recurrent gastrointestinal stromal tumor (GIST): optimal timing of resection.
BACKGROUND
Gastrointestinal stromal tumors (GISTs) are the most common gastrointestinal mesenchymal tumors. The activating mutation in the KIT (c-kit; CD117) proto-oncogene with subsequent tyrosine kinase activation plays a central role in the pathogenesis of GIST. Tyrosine kinase inhibitors are an integral part of GIST therapy. Initial response to neoadjuvant imatinib can be expected in up to 70% of the patients, thus offering an opportunity to surgically treat those with locally advanced primary or recurrent GIST. This favorable response to imatinib, however, is plagued with development of secondary resistance during the course of therapy.


METHODS
We herein report a case of recurrent locally advanced GIST in an elderly man, with excellent performance status, successfully managed with the integration of neoadjuvant targeted therapy and surgery.


CONCLUSIONS
Continued monitoring by a multidisciplinary team, including a surgeon, is vital for the success of neoadjuvant imatinib therapy for unresectable primary or recurrent GIST in the context of emergence of secondary resistance. As such, surgeons should participate in managing imatinib-treated GIST, as resection may become a viable curative option. This case also highlights that major oncologic resections can be safely performed in older persons when their performance status and comorbidities are carefully considered.
Dudeja
Vikas
V
Division of Surgical Oncology, Department of Surgery, Minneapolis VAMC and University of Minnesota, Minneapolis, MN 55455, USA.
Armstrong
Leonard H
LH
Gupta
Pankaj
P
Ansel
Howard
H
Askari
Sabeen
S
Al-Refaie
Waddah B
WB
D000369:Aged, 80 and over; D001549:Benzamides; D001707:Biopsy, Needle; D003131:Combined Modality Therapy; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D005500:Follow-Up Studies; D005743:Gastrectomy / Q000009:adverse effects / Q000379:methods; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000473:pathology / Q000628:therapy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D020360:Neoadjuvant Therapy / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000187:drug effects* / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D018570:Risk Assessment; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D001549:Benzamides; C000715470:MAS1 protein, human; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D000090063:Proto-Oncogene Mas; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit