Green et al. Page 349

Overall survival for advanced ovarian cancer remains poor, particularly for women with platinum-resistant disease. Green and colleagues report the bench to bedside development of a novel cytokine stimulated autologous monocyte therapy for advanced, platinum-resistant or -refractory ovarian cancer. Activated monocytes killed tumor cells in mice via a TRAIL-dependent pathway. Treatment was well tolerated and produced partial responses by RECIST criteria. These findings characterize the mechanism of a novel cellular immunotherapy for ovarian cancer, which is well tolerated with evidence of clinical activity in a heavily pretreated patient population. This therapy may serve as the backbone for a combination immunotherapy regimen incorporating additional agents targeting T-regulatory cells and/or myeloid-derived suppressor cells (MDSCs).

Asleh et al. Page 389

Identifying predictive biomarkers that define the subset of triple-negative breast cancer (TNBC) deriving the most benefit from adjuvant capecitabine is necessary in clinical practice. In this hypothesis-testing study, Asleh and colleagues examined the capacity of candidate RNA biomarkers to predict benefit from extended adjuvant capecitabine using 658 materials from the phase III CIBOMA/2004-01_GEICAM/2003-11 clinical trial. The authors reported that PAM50 nonbasal subtype defines the TNBC subset most likely to benefit from adjuvant capecitabine. If these findings are confirmed in other studies, they could guide the selection of TNBC patients who still benefit from adding adjuvant capecitabine to the selected adjuvant therapy.

Ashley et al. Page 410

Cell-free DNA (cfDNA) sequencing has emerged as a potential biomarker for early detection, diagnosis, disease monitoring, and prognostication in cancer. To define the role of cfDNA in endometrial cancer (EC), Ashley and colleagues prospectively collected cfDNA over a course of 2 years from newly diagnosed EC patients. High-depth sequencing analysis of cfDNA identified EC patients with high-risk of disease progression or recurrence at baseline. Longitudinal cfDNA analysis enabled disease and treatment response monitoring, offering a lead time over imaging in relapse/disease progression detection. These findings warrant further research to ascertain the clinical utility of cfDNA-based risk stratification and disease monitoring.

Serra-Camprubí et al. Page 432

Preclinical models focused on unresectable metastatic cholangiocarcinoma (CCA) are necessary to develop rational treatments. Serra-Camprubí and colleagues described a unique collection of patient-derived models (xenografts and tumoroids) from patients with advanced CCA. Employing these newly developed tools, the authors showed that pathogenic mutations of BRCA2, but not those of IDH1, ARID1A, or BAP1, were associated with a sensitivity to PARP inhibitors in CCA. This collection of patient-derived models may facilitate the early deployment of effective drugs in subgroups of patients with specific molecular features and ultimately help to deliver precision medicine to CCA patient care.