Development of focal adhesion kinase inhibitors in cancer therapy

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase implicated in cancer progression, and plays a vital role in integrating environmental signals from growth factors, extracellular matrix and mechanical forces. As a scaffolding protein, FAK interacts and regulates the activity of many signaling kinases including Src, VEGFR-3, p53, PI3k and IGF-1R. In turn, FAK activity is modulated by a complex network of regulators that presents a number of therapeutic approaches to targeting FAK in cancer therapy. The ATP competitive inhibitors binds directly to FAK kinase domain to abrogate multiple downstream signaling pathways, and this class of agents lead the way in FAK inhibitor clinical development. CFAK-C4 and Y15 represents a novel class of non-ATP dependant, allosteric inhibitors that interrupt protein-protein interactions to achieve anti-cancer effects. The optimal approach to targeting FAK for cancer therapy is currently under investigation. Preliminary efficacy signals from early-phase trials suggest that FAK inhibitors may be best used in combination therapy. In addition to determining dosing schedules that is tolerable by patients, future clinical studies should include mechanistic-based pharmacodynamic studies to determine the biological active dose and explore potential predictive markers. In summary, a rich pipeline of FAK-targeting agents is entering clinical development and has the potential of improving the lives of cancer patients.

Original languageEnglish (US)
Pages (from-to)638-642
Number of pages5
JournalAnti-Cancer Agents in Medicinal Chemistry
Volume11
Issue number7
StatePublished - Sep 1 2011
Externally publishedYes

Fingerprint

Focal Adhesion Protein-Tyrosine Kinases
Neoplasms
Therapeutics
Vascular Endothelial Growth Factor Receptor-3
Proteins
src-Family Kinases
Protein-Tyrosine Kinases
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Appointments and Schedules
Phosphotransferases
Adenosine Triphosphate

Keywords

  • Cancer therapy
  • Drug development
  • FAK
  • Focal adhesion kinase

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Cancer Research

Cite this

Development of focal adhesion kinase inhibitors in cancer therapy. / Ma, Wen Wee.

In: Anti-Cancer Agents in Medicinal Chemistry, Vol. 11, No. 7, 01.09.2011, p. 638-642.

Research output: Contribution to journalArticle

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