Volume 21 Issue 5, May 2024

In 2023, the US FDA approved several new cancer drugs and biologic agents, including seven small-molecule inhibitors, four bispecific T cell engagers, two anti-PD-1 antibodies and one cell therapy product. Regulatory focus areas included analyses of biomarker-positive subgroups that drive efficacy, equipoise in randomized controlled trials and a new authority to require confirmatory trials be underway before accelerated approval.

Increasing evidence indicates that signalling networks activated downstream of oncogenic alterations contribute fundamentally to cancer immune evasion, including by promoting the accumulation of regulatory T (T_reg) cells and other immunosuppressive cells in the tumour microenvironment (TME). Herein, the authors discuss the mechanisms via which cancers engage T_reg cells to evade antitumour immunity, as well as the characteristics of T_reg cells in the TME and their roles in resistance to immune-checkpoint inhibitors. Considering these aspects, they propose the concept of ‘immuno-genomic cancer evolution’ for tumorigenesis and the related paradigm of ‘immuno-genomic precision medicine’, postulating that the specific characteristics of cancer, especially genetic profiles that correlate with particular immunosuppressive networks in the TME, are likely to inform individualized strategies for combining molecularly targeted agents with immunotherapies.

The development and successful phase III testing of the anti-claudin 18.2 antibody zolbetuximab has provided a novel targeted therapy for the 30–40% of patients with strongly claudin 18.2-positive gastric cancers. Furthermore, the development of an effective targeted therapy for a target that does not have a driver role in cancer development provides a novel drug development paradigm. In this Review, the authors describe the development of claudin 18.2-targeted therapies, including zolbetuximab, as well as novel therapies, including chimeric antigen receptor (CAR) T cells, antibody–drug conjugates and bispecific antibodies, all of which have the potential to expand the number of patients who can derive benefit from claudin 18.2-targeted therapies in the near future.

Copper is an essential trace element with inherent redox properties and fundamental roles in a diverse range of biological processes; therefore, maintaining copper homeostasis is crucial. In this Review, the authors discuss new insights into the mechanisms by which disrupted copper homeostasis contributes to tumour initiation and development, including the recently defined concepts of cuproplasia (copper-dependent cell growth and proliferation) and cuproptosis (a mitochondrial pathway of cell death triggered by excessive copper exposure). They also discuss potential strategies to exploit cuproplasia and cuproptosis for the treatment of cancer.

Ovarian cancer, accounting for 4.7% of cancer deaths in women in 2020, remains highly prevalent globally. Nonetheless, owing to changes in environmental exposures, the approach to preventive measures and disease classification, both incidence and mortality have been declining in economically developed countries since the early 2000s. Conversely, parts of Asia and eastern Europe have seen increases in the incidence of ovarian cancer over this period of time. In this Review, the authors summarize the epidemiology of ovarian cancer, including the roles of the various risk factors and the potential for prevention.