Classical oncogenes and tumour suppressors

Although hyperactivation of BRAF has been well-established to drive tumour progression and drug resistance, the role of CRAF in cancer is becoming increasingly relevant. Here, Riaud et al. summarize the various oncogenic roles of CRAF and the potential for CRAF-targeted therapies to improve the clinical outcome for RAF1 altered tumours.

Although p53 was once considered undruggable, in this Review, Peuget et al. discuss the progress made in targeting p53 as a form of cancer therapy with approaches ranging from restoration of mutant p53 function to inhibition of the negative regulator of p53, MDM2, as well as newer strategies, including p53-based mRNA vaccines and antibodies.

In this study, Bhardwaj et al. highlight the mechanistic link between elevated body mass index and breast epithelial cell DNA damage in individuals carrying BRCA mutations.

Mutant gain-of-function p53 is commonly found in human cancers. Huang, Cao, Qian et al. developed and validated the use of multifunctional biomimetic nanoreceptors that bind to and promote the degradation of mutant p53 as a cancer therapy.

In this World View, H. Michael Shepard describes his personal story behind the discovery of trastuzumab, 25 years since its FDA approval for HER2-overexpressing breast cancers.

This Review examines the tissue-specific metabolism and associated therapeutic vulnerabilities of mutant KRAS-driven tumours, providing a comparative discussion of intrinsic metabolism, co-occurring mutations and metabolic interactions in the microenvironment in colorectal, lung and pancreatic cancer.

This Perspective highlights the importance of protein–protein interactions for the oncogenic functions of MYC and discusses how the MYC protein interactome might be exploited therapeutically.

Aberrant signalling of ERBB family members plays an important role in tumorigenesis and in the escape from antitumour immunity in multiple malignancies. This Review discusses the mechanisms by which this signalling affects antitumour immune responses and the potential application of immune-genome precision medicine in this context.