Abstract
Summary:
Src is believed to play an important role in cancer, and several agents targeting Src are in clinical development.
Design:
We reviewed Src structure and function and preclinical data supporting its role in the development of cancer via a PubMed search. We conducted an extensive review of Src inhibitors by searching abstracts from major oncology meeting databases in the last 3 years and by comprehensively reviewing ongoing clinical trials on ClinicalTrials.gov.
Results:
In this manuscript, we briefly review Src structure and function, mechanisms involving Src that lead to the development of cancer, and Src inhibitors and key preclinical data establishing a rationale for clinical application. We then focus on clinical data supporting their use in solid tumor malignancies, a newer arena than their more well-established hematologic applications. Particularly highlighted are clinical trials investigating new biomarkers as well as ongoing studies assessing Src inhibitor activity in biomarker-selected patient populations. We also review newer investigational Src-targeting agents.
Conclusions:
Src inhibitors have shown little activity in monotherapy trials in unselected solid tumor patient populations. Combination studies and biomarker-driven clinical trials are under way.
MeSH terms
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Aniline Compounds / adverse effects
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Aniline Compounds / chemistry
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Aniline Compounds / therapeutic use
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols
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Benzodioxoles / adverse effects
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Benzodioxoles / chemistry
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Benzodioxoles / therapeutic use
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Clinical Trials as Topic
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Dasatinib
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Dose-Response Relationship, Drug
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Humans
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Neoplasms / drug therapy*
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Neoplasms / genetics
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Nitriles / adverse effects
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Nitriles / chemistry
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Nitriles / therapeutic use
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / therapeutic use*
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Pyrimidines / adverse effects
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Pyrimidines / chemistry
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Pyrimidines / therapeutic use
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Quinazolines / adverse effects
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Quinazolines / chemistry
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Quinazolines / therapeutic use
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Quinolines / adverse effects
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Quinolines / chemistry
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Quinolines / therapeutic use
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Thiazoles / adverse effects
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Thiazoles / chemistry
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Thiazoles / therapeutic use
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src-Family Kinases / antagonists & inhibitors*
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src-Family Kinases / chemistry
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src-Family Kinases / genetics
Substances
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Aniline Compounds
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Antineoplastic Agents
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Benzodioxoles
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Nitriles
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Protein Kinase Inhibitors
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Pyrimidines
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Quinazolines
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Quinolines
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Thiazoles
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bosutinib
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saracatinib
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src-Family Kinases
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Dasatinib