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. 2011 Nov;3(1 Suppl):S51-60.
doi: 10.1177/1758834011423540.

Future directions in the evaluation of c-MET-driven malignancies

Johann S de Bono  1 , Timothy A Yap
Affiliations

Future directions in the evaluation of c-MET-driven malignancies

Johann S de Bono et al. Ther Adv Med Oncol. 2011 Nov.

Abstract

The c-MET (mesenchymal-epithelial transition factor) receptor tyrosine kinase is an exciting novel drug target in view of its key role in oncogenesis, as well as its association with disease prognosis in a number of malignancies. Several drugs targeting c-MET are currently showing promise in clinical trials and will hopefully validate positive observations from preclinical studies. The potential efficacy of these different therapeutic agents is expected to be influenced by the mechanism of aberrant hepatocyte growth factor (HGF)/c-MET signaling pathway activation in a particular cancer, but presents a promising strategy for cancer treatment either as a single agent or as part of a combination therapeutic approach. However, there is an ongoing need to improve and accelerate the transition of preclinical research into improved therapeutic strategies for patients with cancer. The main challenges facing the development of HGF/c-MET-targeted agents for cancer treatment include the discovery of rationally designed anticancer drugs and combination strategies, as well as the validation of predictive biomarkers. This paper discusses these issues, with a particular focus on future directions in the evaluation of c-MET-driven malignancies.

Keywords: biomarkers; c-MET; drug development; patient selection; targeted therapy; treatment resistance.

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Figures

Figure 1.
Figure 1.
The shifting focus of old versus new phase I clinical trial designs. PD, pharmacodynamics; PK, pharmacokinetics; MTD, maximum tolerated dose. Reprinted by permission from Macmillan Publishers Ltd: NATURE REVIEWS CANCER, Timothy A. Yap, et al. 2010a;10:514–523, © 2010.
Figure 2.
Figure 2.
Pharmacological audit trail. PARP, poly(ADP)-ribose polymerase; PBMC, peripheral blood mononuclear cell; PhAT, pharmacological audit trail. Adapted by permission from Macmillan Publishers Ltd: NATURE REVIEWS CANCER, Timothy A. Yap, et al. 2010a;10:514–523. © 2010.
See this image and copyright information in PMC

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