A second-generation of genetic-vulnerability-maps in cancer cells

In the pursuit of systematically identifying new therapeutic targets for cancer, various approaches have been explored in pre-clinical drug discovery. Some of these approaches involve large-scale chemical or functional-genomics screens of extensively characterised human cancer cell lines (CLs), with a focus on correlating molecular features - often cancer driver (epi)genomic events - with drug sensitivity and vulnerabilities.

These efforts have generated extensive public datasets encompassing thousands of CLs, their comprehensive characterisations, and responses to individual gene inactivation through CRISPR-Cas9 genome editing. This has laid the groundwork for the collaborative Cancer Dependency Map project, aiming to catalog all intra-cellular cancer dependencies, i.e., genes essential for cancer cell survival.

This endeavour has led to the identification of drug response markers, synthetic lethality cases, and genome-scale prioritisation of novel therapeutic targets. I will introduce our recent contributions in this field, including dedicated computational tools, a second generation of prioritised cancer therapeutic targets, and new data modalities shaping the future of cancer dependency maps.