Volume 16 Issue 2, February 2016

An analysis by Tomasetti and Vogelstein prompted considerable debate about the origins of the genetic mutations that drive tumour initiation. Further fuel to this debate has recently been provided by an analysis from Wuet al.

Nguyen, Pellacaniet al. report data suggesting that a slow multi-step evolutionary process might not be required to generate mammary tumours following KRAS-G12D expression, and that KRAS-G12D-expressing tumours can rapidly accumulate heterogeneous clones.

A new study reports how tracking the evolution of resistance in serial biopsies revealed the molecular mechanisms by which a patient with metastatic non-small-cell lung cancer became resensitized to crizotinib.

A study inCancer Cell reports that the growth of some isocitrate dehydrogenase 1 (IDH1)-mutant cancers is dependent on their addiction to NAD⁺, a metabolic vulnerability that can be targeted by drugs that are already in clinical trials.

Recent studies have shown that germline and somatic mutations in the proofreading exonuclease domains of the replicative DNA polymerases Pol δ and Pol ε are associated with several cancers. This Review summarizes what these mutations are and how they might drive tumorigenesis, and highlights their potential as novel biomarkers and therapeutic targets.

This Analysis article discusses characterization of the kinome in human cancers through genomic, proteomic and functional genomic analyses. In particular, it presents an analysis of cancer genomic data to derive a new census of protein kinase cancer drivers.

Research on the BCL-2-regulated apoptotic pathway has led to the development of small molecules called BH3-mimetics that bind to pro-survival BCL-2 proteins to induce apoptosis of malignant cells. This Timeline article describes the history of research on the BCL-2 family of proteins and their roles in cancer.

The development of therapeutic approaches that target BRCA-mutant tumours has led to the possibility of expanding the range of patients who may benefit from such strategies. Tumours with 'BRCAness', a similar phenotype to germline BRCA-mutant tumours, are increasingly being identified, and this Opinion article discusses the advances and challenges in this context.

Many patients have now received various types of immunotherapy, so we asked three scientists to give their views on whether acquired resistance to immunotherapy exists in patients and the future challenges posed by immunotherapy.