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Advances in technology have enabled the development of several novel antibody–drug conjugates (ADCs) with encouraging clinical activity in patients with advanced-stage solid tumours. Indications for these therapies are expanding rapidly to earlier lines of therapy. Nonetheless, the toxicities of these various agents are not trivial and can be fatal, even in patients with early stage disease. In this Review, the authors summarize the toxicities of ADCs in patients with solid tumours both as monotherapies and in combination with other agents and discuss various ongoing research efforts attempting to optimize the therapeutic index of these agents.

Radiotherapy has several key attributes that make it an attractive combination partner for immunotherapy; however, numerous clinical trials investigating the combination of these two treatment modalities have failed to demonstrate clear improvements in patient outcomes. In this Review, Galluzzi and colleagues discuss the evidence indicating that radiotherapy administered according to standard schedules and target volumes might impair immune fitness and, therefore, propose that adaptation of the radiotherapy regimens to immunotherapy (and not vice versa) might synergistically enhance the antitumour immune response to achieve meaningful clinical benefits.

The authors of this Perspective propose that, with further improvement in detection efficiency, circulating tumour cells (CTCs), which are released early during cancer development, have the potential to be used for the early detection of clinically relevant, aggressive cancers. Thus, use of CTCs as diagnostic biomarkers might improve outcomes by enabling the identification of cancers at a stage at which they are more amenable to treatment while avoiding overtreatment of patients with indolent tumours.

Long-term survival rates of patients with gastric cancer remain low, particularly in Western countries. This lack of progress, among other aspects, is likely to reflect a focus on empirical approaches that fail to account for the heterogeneity of gastric cancers. In this Review, the authors summarize the available evidence on the management of patients with early stage gastric cancers, with an emphasis on understanding the underlying biology in order to improve the outcomes in patients with these historically difficult-to-treat tumours.

The FDA Accelerated Approval pathway, which has been pivotal in enabling early access to new oncology drugs over the past three decades, has recently come under increased scrutiny. New draft guidance published in March 2023 offers several possible solutions to improve this pathway, with the ultimate goal of improving outcomes for patients with cancer, but might also have important limitations.

The effective management of treatment-related events remains an unmet need in oncology. The authors of this Review discuss the underlying biological mechanisms, risk factors, most commonly used pharmacological and non-pharmacological management strategies, and clinical practice guidelines for the most common long-term (continuing beyond treatment) and late or delayed (following treatment) adverse events associated with chemotherapy and other anticancer treatments.

Dysregulation of N⁶-methyladenosine (m⁶A), the most prevalent internal modification in eukaryotic mRNA, is common in various cancer types. The authors of this Review provide an overview of the mechanisms of m⁶A-dependent RNA regulation, summarize current knowledge of their pathological effects and potential utility as biomarkers in cancer, and describe ongoing efforts to develop small-molecule inhibitors of oncogenic m⁶A modifiers.

Cholangiocarcinoma is a malignancy that continues to be associated with a dismal prognosis, and a better understanding of the disease biology is required to improve early detection and treatment strategies. In this Review, the authors describe key scientific and clinical advances made in this area over the past 5 years, encompassing novel insights into the tumour stroma and immune microenvironment, promising progress in developing liquid biopsy approaches for diagnosis and monitoring, clinical translation of molecularly targeted therapies, emerging immunotherapies and reassessment of the potential role of liver transplantation.

Bispecific T cell engagers offer a novel treatment approach for patients with multiple myeloma, although mechanisms of resistance are largely unknown. Here, we discuss the implications of a recent report from Friedrich et al. that highlights the importance of pre-treatment T cell characteristics for a response to the T cell engager elranatamab and how these data might be used to inform future study and trial design.

Between 2016 and 2022, 83 previously approved oncology drugs were covered and reimbursed in China through a value-based pricing negotiation programme, which resulted in substantial price cuts but did not improve the correlation between drug cost and clinical benefit. Herein, we call for an improved, transparent value-based pricing model to better account for high-value innovation in oncology drugs.

Emerging data indicate a central role for the microbiota in all aspects of colorectal cancer (CRC). Despite this general consensus, understanding the role of specific components of the microbiota in such a way that enables the development of clinical interventions or tools to inform clinical decision-making has thus far proved challenging. In this Review, the authors summarize the role of the microbiota in CRC, including in prevention, in interactions with treatment and as a source of novel biomarkers.

Neoadjuvant immune-checkpoint inhibition is a promising emerging treatment strategy that potentially enables patients with a good response to initial therapy to avoid further treatment and the associated toxicity risks, while also identifying those who might require treatment escalation. In this Review, the authors describe treatment personalization strategies based on the initial response to one or more neoadjuvant immune-checkpoint inhibitors and consider the potential to expand this approach beyond patients with melanoma.