The Rho GTPase RAC1 is implicated in cell proliferation and is a potential target in cancer treatment. However, it is also required for normal intestinal homeostasis, so direct targeting of RAC1 could negatively impact that homeostasis. As an alternative approach to direct targeting, Karen Pickering, together with fellow authors, tested indirect targeting of RAC1 via other proteins that affect it, namely Vav2/3 and Tiam1 (A RAC-GEF network critical for early intestinal tumourigenesis). Deletion of all three of these genes profoundly suppressed hyperproliferation, tumourigenesis and RAC1 activity, and importantly, did so without impacting normal intestinal function.

MDM2 is a key regulator of the tumour suppressor protein p53 and is therefore another attractive drug target in cancer. However, designing inhibitors towards the protein's catalytic domain have been hampered by its tendency to aggregate. Here (Identification of a catalytic active but non-aggregating MDM2 RING domain variant), Helge Magnussen and Danny Huang identify a single point mutation that greatly decreases aggregation without affecting MDM2's catalytic activity. This variant should be very useful for developing drugs targeting the catalytic domain.

mTOR is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. Here (The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction), postdoc Ewan Smith and fellow authors use RNA-binding protein capture to identify changes in the RNA–protein interaction network following mTOR inhibition. They find that upon mTOR inhibition, the binding of LARP1 to numerous mRNAs increases, an interaction which the researchers show requires another protein, PABPC1. Importantly, they find that this binding results in translational repression of mRNAs encoding proteins critical for cell growth and survival.

Oncogenic KRAS mutations and inactivation of the APC tumour suppressor often co-occur in colorectal cancer. Despite efforts to target mutant KRAS directly, most therapeutic approaches focus on downstream pathways, albeit with limited efficacy. Here (The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer), postdoc Arafath Najumudeen and fellow researchers show that simultaneous mutation of Apc and Kras in the mouse intestine profoundly rewires cellular metabolism, increasing glutamine consumption. Importantly, the team show that SLC7A5, a glutamine transporter, is critical for colorectal tumourigenesis in models of both early and late stage metastatic disease. Together, these data suggest SLC7A5 as an attractive target for therapy-resistant KRAS mutant colorectal cancer.