Understanding and targeting PARP inhibitor resistance in cancer

Chris started his career with PhD training in disease genetics with John Todd and Richard Gardner at the University of Oxford before carrying out a Postdoctoral Fellowship with Todd at the University of Cambridge. Chris joined the ICR London as a Postdoctoral Fellow with Alan Ashworth in 2000, where he was joint first author on a paper describing the synthetic lethal interaction between BRCA-tumour suppressor genes and PARP inhibitors (Nature 2005), observations that eventually led to the use of these drugs for the treatment of breast, ovarian, prostate and pancreatic cancers.

Later, Chris exploited high-throughput genetic perturbation screens to understand a variety of cancer-related phenotypes including drug sensitivity/resistance and the identification of novel therapeutic targets (e.g. Cancer Cell 2008, Cancer Discov. 2011), a number of which are now being investigated as part of new drug development programmes. Chris has also used multiple approaches to uncover and/or understand clinically-relevant mechanisms of resistance to DNA repair inhibitors (e.g. Nat Commun. 2018, Cancer Discov. 2020) and to identify novel synthetic lethal approaches that target hard-to-treat cancers, including those with ARID1A, Rb or E-cadherin defects (e.g. Cancer Discov. 2018).

More recently, Chris has focused on using high-throughput genetic perturbation screens to understand the principles that govern the robustness of synthetic lethal interactions (e.g. Elife 2020). The impact of the work led by Lord is demonstrated by the multiple biomarkers of drug sensitivity/resistance and novel synthetic lethal approaches to the treatment of ARID1A, Rb or E-cadherin defective cancers now being assessed in clinical trials.