Emergence of imatinib resistance associated with downregulation of C-Kit expression in recurrent gastrointestinal stromal tumor (GIST): Optimal timing of resection

Vikas Dudeja, Leonard H. Armstrong, Pankaj Gupta, Howard Ansel, Sabeen Askari, Waddah B. Al-Refaie

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Introduction: 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. Case description: 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. Discussion: 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.

Original languageEnglish (US)
Pages (from-to)557-561
Number of pages5
JournalJournal of Gastrointestinal Surgery
Volume14
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

Gastrointestinal Stromal Tumors
Down-Regulation
Neoadjuvant Therapy
Protein-Tyrosine Kinases
Proto-Oncogenes
Imatinib Mesylate
Comorbidity
Mutation
Therapeutics

Keywords

  • C-kit
  • Drug resistance
  • Elderly
  • Gastrointestinal stromal tumor
  • Imatinib mesylate
  • Neoplasm
  • Surgery

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

Cite this

Emergence of imatinib resistance associated with downregulation of C-Kit expression in recurrent gastrointestinal stromal tumor (GIST) : Optimal timing of resection. / Dudeja, Vikas; Armstrong, Leonard H.; Gupta, Pankaj; Ansel, Howard; Askari, Sabeen; Al-Refaie, Waddah B.

In: Journal of Gastrointestinal Surgery, Vol. 14, No. 3, 01.03.2010, p. 557-561.

Research output: Contribution to journalArticle

Dudeja, Vikas ; Armstrong, Leonard H. ; Gupta, Pankaj ; Ansel, Howard ; Askari, Sabeen ; Al-Refaie, Waddah B. / Emergence of imatinib resistance associated with downregulation of C-Kit expression in recurrent gastrointestinal stromal tumor (GIST) : Optimal timing of resection. In: Journal of Gastrointestinal Surgery. 2010 ; Vol. 14, No. 3. pp. 557-561.
@article{52296447276f43439aad0a66f1b23389,
title = "Emergence of imatinib resistance associated with downregulation of C-Kit expression in recurrent gastrointestinal stromal tumor (GIST): Optimal timing of resection",
abstract = "Introduction: 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. Case description: 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. Discussion: 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.",
keywords = "C-kit, Drug resistance, Elderly, Gastrointestinal stromal tumor, Imatinib mesylate, Neoplasm, Surgery",
author = "Vikas Dudeja and Armstrong, {Leonard H.} and Pankaj Gupta and Howard Ansel and Sabeen Askari and Al-Refaie, {Waddah B.}",
year = "2010",
month = "3",
day = "1",
doi = "10.1007/s11605-009-1121-2",
language = "English (US)",
volume = "14",
pages = "557--561",
journal = "Journal of Gastrointestinal Surgery",
issn = "1091-255X",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Emergence of imatinib resistance associated with downregulation of C-Kit expression in recurrent gastrointestinal stromal tumor (GIST)

T2 - Optimal timing of resection

AU - Dudeja, Vikas

AU - Armstrong, Leonard H.

AU - Gupta, Pankaj

AU - Ansel, Howard

AU - Askari, Sabeen

AU - Al-Refaie, Waddah B.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Introduction: 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. Case description: 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. Discussion: 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.

AB - Introduction: 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. Case description: 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. Discussion: 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.

KW - C-kit

KW - Drug resistance

KW - Elderly

KW - Gastrointestinal stromal tumor

KW - Imatinib mesylate

KW - Neoplasm

KW - Surgery

UR - http://www.scopus.com/inward/record.url?scp=77950517698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950517698&partnerID=8YFLogxK

U2 - 10.1007/s11605-009-1121-2

DO - 10.1007/s11605-009-1121-2

M3 - Article

C2 - 20033343

AN - SCOPUS:77950517698

VL - 14

SP - 557

EP - 561

JO - Journal of Gastrointestinal Surgery

JF - Journal of Gastrointestinal Surgery

SN - 1091-255X

IS - 3

ER -