Selected Articles from This Issue

Biomarkers to define patients unlikely to derive benefit from endocrine therapy combined with CDK4/6 inhibitor are limited. Davis and colleagues performed a comprehensive biomarker analysis from a phase II clinical trial to evaluate whole-exome sequencing and genome-wide copy-number burden using circulating tumor DNA. These studies defined a subset of patients with high tumor mutational burden and elevated copy-number burden with shorter progression-free survival, and these assays offer opportunities as noninvasive tools for baseline tumor assessment and serial disease monitoring. Prospective studies are needed to define novel treatment strategies for patients with genomically complex disease.

The heterogeneity of HCC leads to a limited objective response rate to lenvatinib, and predicting the response to lenvatinib is clinically challenging. Bo and colleagues first performed this study to predict the response to lenvatinib monotherapy for unresectable HCC with machine learning radiomics. Significant differences in radiomics features were identified between responders and nonresponders treated with lenvatinib. Valuable machine learning radiomics models were constructed to predict the response to lenvatinib, showing satisfactory predictive performance. This provides a new indication that machine learning radiomics may serve as a useful noninvasive and easy-to-use tool to aid clinical decision making.

Mutations in isocitrate dehydrogenase 1 (mIDH1) are prevalent in low-grade gliomas. To identify gene targets altered by mIDH1-mediated epigenetic reprogramming, Carney and colleagues treated radioresistant mIDH1 glioma cells, with a specific mIDH1 inhibitor. They identified that Zinc Finger MYND type-containing 8 (ZMYND8) was epigenetically regulated in human and mouse mIDH1 glioma models. Suppression of ZMYND8 by shRNA or genetic knockout sensitized mIDH1 gliomas to radiation. Notably, inhibitors against ZMYND8-interacting partners HDAC and PARP were also shown to promote tumor cell death. These data uncover a novel epigenetic vulnerability for IDH-mutant gliomas and highlights ZMYND8’s role in DNA repair and radioresistance.

The immune system's role in breast cancer has mainly been studied among ER-negative/HER2-positive subtypes, and it is unclear how immunological biomarkers should be used in ER-positive breast cancer. Stenmark Tullberg and colleagues set out to identify tumor characteristics that predict immune responsiveness in a training cohort. The findings were applied to a randomized radiotherapy cohort dominated by ER-positive tumors with the hypothesis that predicting the prognostic implications of an immune infiltrate in low-risk patients is possible. The authors found that tumor characteristics associated with proliferation predicted an activated immune infiltrate and that such patients are candidates for radiotherapy de-escalation.