Why tyrosine kinase inhibitor resistance is common in advanced gastrointestinal stromal tumors

Cristian Tomasetti; George D. Demetri; Giovanni Parmigiani

doi:10.12688/f1000research.2-152.v1

Why tyrosine kinase inhibitor resistance is common in advanced gastrointestinal stromal tumors

Cristian Tomasetti, George D. Demetri, Giovanni Parmigiani

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Background: Most patients with advanced gastrointestinal stromal tumors (GIST) develop drug resistance to tyrosine kinase inhibitors (TKIs) within two years of starting therapy, whereas most chronic myeloid leukemia (CML) patients in chronic phase still exhibit disease control after a decade on therapy. This article aims to explain this divergence in long term outcomes. Methods and results: By combining clinical and experimental observations with mathematical formulas we estimate that, in advanced GIST, the genetic changes responsible for resistance are generally already present at disease detection. Conclusion: This result has relevant clinical implications by providing support for the exploration of combination therapies.

Original language	English (US)
Article number	152.v1
Journal	F1000Research
Volume	2
DOIs	https://doi.org/10.12688/f1000research.2-152.v1
State	Published - Jul 9 2013
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
Pharmacology, Toxicology and Pharmaceutics(all)

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10.12688/f1000research.2-152.v1

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title = "Why tyrosine kinase inhibitor resistance is common in advanced gastrointestinal stromal tumors",

abstract = "Background: Most patients with advanced gastrointestinal stromal tumors (GIST) develop drug resistance to tyrosine kinase inhibitors (TKIs) within two years of starting therapy, whereas most chronic myeloid leukemia (CML) patients in chronic phase still exhibit disease control after a decade on therapy. This article aims to explain this divergence in long term outcomes. Methods and results: By combining clinical and experimental observations with mathematical formulas we estimate that, in advanced GIST, the genetic changes responsible for resistance are generally already present at disease detection. Conclusion: This result has relevant clinical implications by providing support for the exploration of combination therapies.",

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AU - Demetri, George D.

AU - Parmigiani, Giovanni

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N2 - Background: Most patients with advanced gastrointestinal stromal tumors (GIST) develop drug resistance to tyrosine kinase inhibitors (TKIs) within two years of starting therapy, whereas most chronic myeloid leukemia (CML) patients in chronic phase still exhibit disease control after a decade on therapy. This article aims to explain this divergence in long term outcomes. Methods and results: By combining clinical and experimental observations with mathematical formulas we estimate that, in advanced GIST, the genetic changes responsible for resistance are generally already present at disease detection. Conclusion: This result has relevant clinical implications by providing support for the exploration of combination therapies.

AB - Background: Most patients with advanced gastrointestinal stromal tumors (GIST) develop drug resistance to tyrosine kinase inhibitors (TKIs) within two years of starting therapy, whereas most chronic myeloid leukemia (CML) patients in chronic phase still exhibit disease control after a decade on therapy. This article aims to explain this divergence in long term outcomes. Methods and results: By combining clinical and experimental observations with mathematical formulas we estimate that, in advanced GIST, the genetic changes responsible for resistance are generally already present at disease detection. Conclusion: This result has relevant clinical implications by providing support for the exploration of combination therapies.

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Why tyrosine kinase inhibitor resistance is common in advanced gastrointestinal stromal tumors

Abstract

ASJC Scopus subject areas

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