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The identification of biomarkers that can predict therapeutic outcomes in response to PD-1 or PD-L1 immune checkpoint inhibitors remains an unmet need in the treatment of NSCLC and urothelial cancer. To identify a predictive biomarker for durvalumab, an anti-PD-L1 monoclonal antibody, Higgs and colleagues performed RNA sequencing of biopsies from NSCLC and urothelial cancer patients enrolled in a nonrandomized phase Ib/II clinical trial (NCT01693562). Their results demonstrate that gene expression levels of four IFNγ-inducible mRNAs correlate with improved clinical outcomes in durvalumab-treated patients with NSCLC or urothelial cancer. This IFNγ gene signature may augment the predictive value of PD-L1 and other biomarkers in identifying those cancer patients who are most likely to respond to therapy with durvalumab or other immune checkpoint inhibitors, independently of PD-L1 assessed by immunohistochemistry.To determine whether the 21-gene recurrence score can predict benefit of postmastectomy radiotherapy (PMRT) in women with ER-positive T1-2 N1 breast cancer, Goodman and colleagues performed an observational cohort study using the National Cancer Database as a discovery cohort and the SEER registry as a validation cohort. Women with low-risk recurrence scores derived a significant survival benefit from PMRT, while women with intermediate- and high-risk scores did not. Women at the lowest risk of distant failure may, therefore, derive the greatest benefit from aggressive locoregional therapy with PMRT.The poor response of advanced stage ovarian clear cell carcinoma (OCCC) towards platinum-based chemotherapy urges alternative therapeutic strategies. Caumanns and colleagues performed a comprehensive kinome-wide screen in a large set of OCCC patients and reported numerous genomic alterations related to mTORC1/2 activation. Ubiquitous expression of mTORC1/2 downstream target p-S6 in OCCC patients and the high sensitivity of OCCC cell lines and patient-derived xenografts to mTORC1/2 inhibitors indicate the clinical relevance of these genomic alterations. These findings propose further exploration of mTORC1/2 inhibitors, currently being evaluated in phase II clinical trials in OCCC patients.Epithelial-to-mesenchymal transition (EMT) plays a critical role in tumor invasion and metastasis. Integrating findings from a human papillomavirus-16 E6/E7 oncoprotein driven model of invasion with analysis of patient samples and TCGA RNA-seq, Srivastava and colleagues identify Slug as the major modulator of EMT in head and neck squamous cell carcinoma (HNSCC). Expression of the p63 isoform ΔNp63γ is necessary and sufficient to induce Slug and EMT, which requires signaling through the activity of another p63 target Src. Elevated expression of Src associates with worse outcome in HNSCC; thus clinical efforts targeting Src hold promise in poor prognosis HNSCC.