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Drug development and clinical trials—the path to an approved cancer drug

Abstract

Advances in our understanding of cancer biology have led to the discovery of a spectrum of new therapeutic targets. However, despite remarkable progress in the identification and characterization of novel mechanisms of the oncogenic process, the success rate for approval of oncology drugs remains low relative to other therapeutic areas. Innovative preclinical and clinical approaches, such as the use of advanced genomic technologies, as well as branched adaptive clinical trial designs, have the potential to accelerate the development and approval of highly effective oncology drugs, along with a matching diagnostic test to identify those patients most likely to benefit from the new treatment. To maximize the effectiveness of these new strategies, close collaboration between academic, industry, and regulatory agencies will be required. In this Review, we highlight new approaches in preclinical and clinical drug development that will help accelerate approval of drugs, and aim to provide more-effective treatments alongside companion diagnostic tests to ensure the right treatment is given to the right patient.

Key Points

  • Traditional approaches to preclinical and clinical development of anticancer agents have a poor track record of success and are not sustainable from an industry perspective

  • There have been significant advances in the preclinical development of targeted anticancer therapies that may improve the clinical success rate

  • New clinical trial approaches are available that may improve selection of the best dose, as well as better identify responsive patients via co-development of a companion diagnostic test

  • There are increasing examples of academic–industry collaborations to develop public databases containing linked clinical and biomarker information, which have the potential to accelerate development of highly effective anticancer drugs

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Figure 1: Research and development spending and sales for leading pharmaceutical companies from 1980 to 2008.
Figure 2: ShRNA-based synthetic lethality and enhancer screens to identify novel cancer targets.
Figure 3: Wee1 and PARP inhibitors are examples of synthetic-lethal interactions in TP53 and BRCA1 deficient backgrounds, respectively.

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Both authors researched data for the article, made a considerable contribution to the discussion of the content, wrote the manuscript and edited and revised the article before submission.

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Correspondence to Eric H. Rubin.

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E. H. Rubin and D. G. Gilliland are employees at Merck.

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Rubin, E., Gilliland, D. Drug development and clinical trials—the path to an approved cancer drug. Nat Rev Clin Oncol 9, 215–222 (2012). https://doi.org/10.1038/nrclinonc.2012.22

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