Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

KIT mutations in GIST.

Jonathan A Fletcher1, Brian P Rubin

  • 1Brigham and Women's Hospital, 75 Francis Street, Thorn 5, Boston, MA 02115, USA. jfletcher@partners.org

Current Opinion in Genetics & Development
|January 9, 2007
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

System for study of diverse cellular composition in alveolar rhabdomyosarcoma.

Scientific reports·2026
Same author

Dissecting the oncogenic function of YAP1 and WWTR1 fusion proteins in mammary epithelial cells.

Cancer letters·2026
Same author

CD117-Targeted Intraoperative Imaging of Gastrointestinal Stromal Tumor Using a Stem-Cell-Factor-Labeled Fluorophore.

Advanced nanobiomed research·2025
Same author

Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout.

Cancers·2025
Same author

AMPK Signaling Regulates Epithelioid Hemangioendothelioma Cell Growth.

Cancers·2025
Same author

Ossifying Spindled and Epithelioid Tumor: A Novel Soft Tissue Tumor.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc·2025
Same journal

Transcription regulation of cell fate plasticity - from embryonic development to tissue regeneration.

Current opinion in genetics & development·2026
Same journal

Shared molecular and cellular programs during regeneration of glandular epithelia.

Current opinion in genetics & development·2026
Same journal

Lineage tracing in human cortical development.

Current opinion in genetics & development·2026
Same journal

Cis-regulatory strategies in developmental patterning.

Current opinion in genetics & development·2026
Same journal

GABAergic neuron fate specification and lineage allocation: from development to disorder.

Current opinion in genetics & development·2026
Same journal

Active processes shape and move the genome and nucleoplasm.

Current opinion in genetics & development·2026
See all related articles

Gastrointestinal stromal tumors (GISTs) are often treated with imatinib and sunitinib, but resistance develops. New therapies like nilotinib and HSP90 inhibitors show promise for overcoming this resistance in GIST patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Most gastrointestinal stromal tumors (GISTs) harbor oncogenic KIT or PDGFRA mutations.
  • KIT and PDGFRA kinase inhibitors, such as imatinib and sunitinib, are effective treatments for inoperable GIST.
  • Clinical resistance to imatinib and sunitinib is a significant challenge in GIST management.

Purpose of the Study:

  • To explore therapeutic strategies for overcoming imatinib and sunitinib resistance in GIST.
  • To investigate the potential of novel kinase inhibitors and targeted therapies for resistant GIST mutations.

Main Methods:

  • Review of preclinical studies on GIST resistance mechanisms.
  • Analysis of therapeutic approaches targeting secondary mutations in KIT and PDGFRA.

Related Experiment Videos

  • Evaluation of alternative treatments including potent kinase inhibitors, HSP90 inhibitors, and transcriptional repressors.

    • Main Results:

    • Imatinib and sunitinib resistance in GIST typically arises from secondary mutations in KIT and/or PDGFRA kinase domains.
    • Preclinical data suggest potent kinase inhibitors like nilotinib can inactivate mutant kinase proteins.
    • HSP90 inhibitors and KIT transcriptional repressors (e.g., flavopiridol) offer alternative strategies by targeting mutant protein degradation or expression.

    Conclusions:

    • Secondary mutations in KIT and PDGFRA are the primary cause of imatinib and sunitinib resistance in GIST.
    • Nilotinib, HSP90 inhibitors, and flavopiridol represent promising therapeutic avenues for treating resistant GIST.
    • Further research into these novel agents is warranted for improved GIST patient outcomes.