In Cancer Discovery this week, researchers in France and Lebanon say drug-induced degradation of oncoproteins is an unexpected weakness of cancer cells. Many targeted cancer treatments inhibit the enzymatic activity of kinases, an approach that has yielded clinical improvements, but few cures, the authors write. Other drugs, "which selectively elicit proteasome-dependent degradation of oncoproteins, induce the loss of cancer cell self-renewal and promote cell differentiation and/or apoptosis," improving clinical outcome in many cases, they add. Several transcription factors, nuclear receptors, and fusion proteins, which drive cancer growth, could then be candidates for proteolysis-based drug-discovery. "Leukemia- or sarcoma-associated fusion proteins are the best candidates for small-molecule screens aimed at initiating oncoprotein degradation," the researchers suggest.
Also in Cancer Discovery this week, researchers in the US and Europe say that C-Raf is required for the initiation of lung cancer by K-Ras. The team investigated the roles of two Raf kinases — B-Raf and C-Raf — in Ras oncogenesis, and found that C-Raf is required for the proliferation of K-Ras in primary epithelial cells. In addition, a lung cancer mouse model showed that C-Raf is "essential for tumor initiation by oncogenic K-Ras," the authors write. "Our findings reveal that K-Ras elicits its oncogenic effects primarily through C-Raf and suggest that selective C-Raf inhibition could be explored as a therapeutic strategy for K-Ras-dependent cancers."
And finally in Cancer Discovery this week, Boston researchers write that ovarian cancer spheroids use myosin-generated force to clear the mesothelium and implant themselves into the mesothelial monolayer on the walls of peritoneal and pleural cavity organs. The team developed a live, image-based in vitro model to monitor interactions between tumor spheroids and mesothelial cells, and found that the spheroids use "integrin- and talin-dependent activation of myosin and traction force to promote displacement of mesothelial cells" from underneath themselves. "These results suggest that ovarian tumor cell clusters gain access to the submesothelial environment by exerting force on the mesothelial cells lining target organs, driving migration and clearance of the mesothelial cells," the team adds.