The therapeutic options currently available for patients with metastatic renal cell carcinoma (RCC) include immune-checkpoint inhibitors, novel targeted agents and combination strategies, and thus optimal patient selection and treatment sequencing are important. The authors review relevant aspects of the molecular biology of metastatic RCC, with an emphasis on biomarkers, and suggest tailored algorithms to individualize and guide treatment approaches

The authors of this Review propose a new model in which dynamic fluctuations of protein expression at the single-cell level and longitudinal reshaping of the cellular state at the cell-population level explain the process of therapeutic resistance development in patients with melanoma.

The metabolic conditions in tumours can result in phenotypic reprogramming of non-tumour cells, including immune cells, in the tumour microenvironment. This Review provides an overview of the pathways of cancer metabolism that intersect with immunometabolism, typically resulting in immunosuppression, with a focus on how these metabolic pathways could be targeted in order to enhance anticancer immunity and immunotherapy.

Immunotherapy with immune-checkpoint inhibitors (ICIs) is a new pillar in the treatment of cancer but can a have range of immune-related adverse effects, including some rare neurological toxicities that constitute paraneoplastic neurological syndromes (PNSs). In this Review, the authors provide an overview of PNSs, the associations of these conditions with ICI therapy and recommendations for the prevention and management of ICI-associated PNSs.

The development of chimeric antigen receptor (CAR) T cell therapy is an important advance in the treatment of cancer. Herein, the authors outline the key limitations of CAR T cell therapy, with a focus on mechanisms of resistance, and discuss strategies to improve the efficacy and broaden the applicability of this promising therapeutic approach.

Patients with lymphoma typically receive chemotherapy as the first-line treatment. However, patients who fail to respond or develop relapsed disease often have poor outcomes. In this Review, the authors summarize the available data on therapeutics designed to modulate epigenetic changes, including DNA methylation and histone acetylation, in patients with lymphoma and describe the most promising directions of future research.

Breast oncologists are intimately familiar with managing treatment-related adverse events of endocrine, cytotoxic and targeted therapies, but the approval of immune-checkpoint inhibitors (ICIs) for metastatic triple-negative breast cancer (TNBC) poses new challenges. Herein, we discuss the safety of ICIs in metastatic TNBC, with an emphasis on immune-related adverse events.