Highlights of This Issue

Abstract

The clinical impact of mechanisms of acquired resistance to anti-EGFRs in mCRC is poorly understood. In chemorefractory patients treated with anti-EGFRs, Pietrantonio and colleagues performed NGS and MET/HER2 in situ hybridization on tumor samples obtained at baseline and at disease progression. Matched ctDNA was also analyzed. RAS and BRAF mutations and HER2 and MET amplifications were the most frequent alterations, but concordance among tumor and liquid biopsies was not always detectable. Intra- and interlesion heterogeneity of resistance mechanisms was observed. These results could have clinical implications to select the most appropriate therapy in patients who develop acquired resistance to anti-EGFRs.A major challenge for cancer immunotherapy has been the eradication of large solid tumors. In a major advance towards this goal, Slaney and colleagues describe an approach using adoptive cell transfer and an oncolytic viral vaccine, which led to extensive T-cell proliferation and recruitment of endogenous immunity to mediate complete and durable regression of established tumors in mice. Notably, the study was performed in syngeneic, self-antigen models, which permitted the stringent preclinical assessment of efficacy and potential toxicities of this approach, to enable progression of the approach towards the clinic.Genomic and transcriptomic analysis are starting to define the landscape of male breast cancer. In an analysis of over 700 male breast cancer cases across four independent datasets at the transcriptomic and immunohistochemical levels, increased expression of translational initiation pathway genes, eIF4E and eIF5, were independent predictors of reduced survival. Samples from a male patient with breast cancer who was treated with an investigational combination of BEZ235 and everolimus, which target this pathway, showed a marked reduction in eIF4E and eIF5 expression, accompanied by improved survival, suggesting this pathway may be tractable.Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third most common cause of cancer-related death in the Asia-Pacific region. Sorafenib monotherapy, the current standard of care for advanced HCC, provides only modest survival benefit; more effective systemic therapies are needed. Results reported by Yau and colleagues from a phase I/II clinical trial of foretinib as a first-line monotherapy for advanced HCC in Asian patients show promising antitumor activity with acceptable safety and tolerability. Further investigation of the relative efficacy of foretinib and standard of care treatment in advanced HCC is warranted.