Current status of SRC inhibitors in solid tumor malignancies

Oncologist. 2011;16(5):566-78. doi: 10.1634/theoncologist.2010-0408. Epub 2011 Apr 26.

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.

Publication types

  • Review

MeSH terms

  • Aniline Compounds / adverse effects
  • Aniline Compounds / chemistry
  • Aniline Compounds / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols
  • Benzodioxoles / adverse effects
  • Benzodioxoles / chemistry
  • Benzodioxoles / therapeutic use
  • Clinical Trials as Topic
  • Dasatinib
  • Dose-Response Relationship, Drug
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Nitriles / adverse effects
  • Nitriles / chemistry
  • Nitriles / therapeutic use
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / chemistry
  • Pyrimidines / therapeutic use
  • Quinazolines / adverse effects
  • Quinazolines / chemistry
  • Quinazolines / therapeutic use
  • Quinolines / adverse effects
  • Quinolines / chemistry
  • Quinolines / therapeutic use
  • Thiazoles / adverse effects
  • Thiazoles / chemistry
  • Thiazoles / therapeutic use
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / chemistry
  • src-Family Kinases / genetics

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Benzodioxoles
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Quinazolines
  • Quinolines
  • Thiazoles
  • bosutinib
  • saracatinib
  • src-Family Kinases
  • Dasatinib