Volume 11 Issue 7, July 2011

A new study describes a novel mechanism of resistance to BCR–ABL1 inhibitors and suggests a therapeutic strategy for resensitization.

Semenza and colleagues identify a positive feedback loop between the pyruvate kinase PKM2 and HIF1 that may explain how PKM2 can promote metabolic reprogramming of cancer cells.

Dieter Saur and colleagues show that a cathepsin-activatable probe can be used to detect and diagnose early stages of pancreatic cancer.

Tumorigenesis by the receptor tyrosine kinase MET requires not only activation but also increased localization and signalling on endosomes.

Pollard and colleagues have examined the origin and function of metastasis-associated macrophages and implicated the chemokine CCL2 in their recruitment.

The tumour suppressor WTX regulates mesenchymal progenitor cell fate and lineage specification.

Two papers identify new modulators of ERα expression, which has implications for responses of ERα⁺breast cancer to endocrine therapy.

Two recent papers have shown that the E3 ubiquitin ligase COP1 is a tumour suppressor.

Interstrand crosslinks (ICLs) are a type of DNA damage that is induced by various chemotherapeutics, such as cisplatin. This Review discusses how these lesions are repaired through multiple pathways, including the Fanconi anaemia pathway, and how ICL repair mediates sensitivity to these drugs.

Recent studies have identified frequent inactivating mutations in different SWI/SNF subunits in several types of cancer, highlighting the tumour suppressor roles of these chromatin remodellers. This Review discusses the current knowledge regarding inactivating mutations, and silencing, of SWI/SNF subunits in cancer, the molecular mechanisms of their tumour suppressor functions and possibilities for therapeutic intervention in SWI/SNF-mutant cancers.

Research into basic developmental biology has frequently yielded insights into cancer biology. This is particularly true for the Hedgehog (HH) pathway, and both naturally occurring and synthetic inhibitors of HH signalling show great promise. However, it remains unclear how many cancers will ultimately benefit from these new, molecularly targeted therapies.

Senescence is becoming increasingly appreciated as a powerful mechanism of tumour suppression. This Opinion article discusses how senescence may be capitalized on for therapeutic benefit, and includes the defining features of senescence signalling pathways and the potential molecular strategies and considerations for senescence induction.

This article describes the importance of key physical and mechanical processes at each step of the metastatic cascade. The emerging insight into these physical interactions may lead to new approaches to developing cancer diagnostics and therapies.

This article introduces some preliminary mathematical models of the basic decision circuits in breast cancer cells, with a view to understanding in greater detail their susceptibility or resistance to endocrine therapy.