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In this issue, read about therapeutic targeting of apoptosis, T cell-engaging therapies, and the SWI/SNF complex in cancer.
Image of a primary human invasive ductal carcinoma tissue section stained for immune cells supplied by Ms Sayali Onkar, University of Pittsburgh School of Medicine, and Dr. Marion Joy, National Surgical Adjuvant Breast and Bowel Project. Cover design: Simon Bradbrook.
The coronavirus disease 19 (COVID-19) pandemic has become the focus of attention worldwide, and herein we seek to highlight the potential problem of ‘collateral mortality’ from delayed or deferred treatments in patients with cancer. We propose potential solutions to ensure continuity of care in the field of surgical oncology.
Early published data on COVID-19 in patients with cancer are being referenced in clinical guidelines, despite methodological flaws that limit the quality of much of this evidence. In the next phase of research in this area, we argue that the quality of observational evidence should be prioritized over speed of publication.
Effective anticancer therapies typically activate antitumour immunity, predominately mediated by T cells in the tumour microenvironment. Here, we discuss the roles of B cells and tertiary lymphoid structures in the context of chemotherapy-induced complement activation, which results in the induction of a B cell subset that modulates T cell function.
The authors of this Review present the main pathways that regulate apoptosis as well as other signalling pathways that interact with them, highlighting actionable molecular targets for anticancer therapy. They also provide an overview of therapeutic agents exploiting apoptosis currently in clinical translation and known mechanisms of resistance to these agents.
The use of bispecific antibodies to engage cells of the immune system that are cytotoxic to cancer cells is a major focus of cancer immunotherapy, with approvals for the treatment of acute lymphoblastic leukaemia. Here, the authors review the clinical results obtained with bispecific antibodies to date. They also discuss the challenges associated with this therapeutic approach and the proposed solutions aimed at preventing or minimizing toxicities, countering immune escape and broadening the indications for these treatments.
Mutations in genes encoding subunits of the SWI/SNF chromatin-remodelling complexes occur in almost 25% of all cancers. Herein, Mittal and Roberts discuss the mechanisms by which these mutations might promote cancer and describe the associated vulnerabilities that provide opportunities for targeted therapy or immunotherapy with immune-checkpoint inhibitors.