Taking advantage of drug resistance, a new approach in the war on cancer

Abstract

Identification of the driver mutations in cancer has resulted in the development of a new category of molecularly targeted anti-cancer drugs. However, as was the case with conventional chemotherapies, the effectiveness of these drugs is limited by the emergence of drug-resistant variants. While most cancer therapies are given in combinations that are designed to avoid drug resistance, we discuss here therapeutic approaches that take advantage of the changes in cancer cells that arise upon development of drug resistance. This approach is based on notion that drug resistance comes at a fitness cost to the cancer cell that can be exploited for therapeutic benefit. We discuss the development of sequential drug therapies in which the first therapy is not given with curative intent, but to induce a major new sensitivity that can be targeted with a second drug that selectively targets the acquired vulnerability. This concept of collateral sensitivity has hitherto not been used on a large scale in the clinic and holds great promise for future cancer therapy.

Keywords

cancer / drug resistance / genetic screens / senescence / targeted therapy

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Acknowledgements

The work of the authors is supported by the Oncode Institute, which is financed in part by the Dutch Cancer Society (KWF) and by the gravitation program CancerGenomics.nl from the Netherlands Organisation for Scientific Research (NWO).

Compliance with ethics guidelines

Liqin Wang and Rene Bernards declare no competing or financial interests. This manuscript does not involve any research protocols requiring approval by the relevant ethical committee or institutional review board.

Open Access

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2018 The Author(s) 2018. This article is published with open access at link.springer.com and journal.hep.com.cn