Identifying New Targets for Personalised Cancer Therapy

Abstract

Personalised medicine requires the use of patient‐specific information to predict individual responses to disease treatment. Consequently, this approach requires the diagnostic ability to stratify patients based on their potential to benefit from a specific treatment (as opposed to an alternative) and the availability of molecularly targeted therapies. On the basis of the heterogeneity of the disease, cancer diagnosis and therapy is currently at the forefront of personalised medicine. Cancer therapy is currently undergoing a significant paradigm change, from nonspecific cytotoxic agents to considerably more specific approaches based on the unique molecular features of cancer cells. The identification and validation of disease relevant targets is crucial for the development of molecularly targeted anticancer therapies. Our advancing understanding of the molecular basis of cancer in tandem with novel approaches to interfere with signal transduction pathways have opened new horizons for anticancer target discovery. Specifically, the image‐based large‐scale analysis of cellular phenotypes that arise from genetic or chemical perturbations paved the way for the identification and validation of disease relevant molecular targets independent of preconceived notions of mechanistic relationships.

Key Concepts:

  • Cancer therapy is undergoing a change from nonspecific cytotoxic to molecularly targeted treatment.

  • Targeted cancer therapies need new relevant targets.

  • A good therapeutic target is essential and specific.

  • Targeting specific molecular targets are expected to be beneficial only for a subset of patients.

  • Companion diagnostics based on specific biomarkers is essential to guide treatment decisions.

  • Targeted treatment has to be intimately linked to the causal changes for each neoplasm.

  • The selection of appropriate combinations of molecular targets specific for different cancers will be essential to develop successful anticancer therapies.

  • Image‐based high content screening allows for the identification of disease relevant molecular targets independent of preconceived notions of mechanistic relationships.

Keywords: cancer; target discovery; high content screening; drug resistance; imatinib; personalized medicine; FOXO; chemical genetics

Figure 1.

Proposed schematic for the novel therapeutic vemurafenib and the corresponding companion diagnostics as a paradigm for molecularly targeted therapies in modern personalised medicine.

Figure 2.

A schematic diagram demonstrating how following melanoma diagnosis, a personalised medicine approach can be used to identify the patient population that would respond to treatment with vemurafenib (those who harbour constitutive BRAF v600‐positive tumours).

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Link, W, Madureira, PA, and Hill, R(May 2013) Identifying New Targets for Personalised Cancer Therapy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0024865]