Perspectives in 2025

In this Perspective, de Magalhães explores the evolutionary relationship between cancer and ageing, proposing that the need to minimize cancer risk early in life may contribute to tissue degeneration later on, representing a trade-off that constrains the evolution of longer lifespans.

Allogeneic haematopoietic stem cell transplantation remains the cornerstone of curative treatment for advanced myeloid malignancies. In this Perspective, Foldvari et al. propose that T cells engineered to express tumour-reactive T cell receptors (TCRs) may offer a safer and more effective alternative. They outline key considerations for identifying and validating suitable target antigens and matching TCRs, and for advancing these therapies towards clinical application.

In this Perspective, Lazure and Gomes argue that metabolic changes that occur as a result of ageing may shape tumour initiation and progression and the development of metastatic disease.

Comparative oncology combines evolutionary biology, ecology, veterinary medicine and clinical oncology to better understand cancer, for example, by identifying the molecular and cellular mechanisms underlying the remarkable cancer resistance of some taxa. Therefore, this Perspective by Vincze et al. calls for the increased use of non-conventional model organisms in cancer research to advance cancer prevention and treatment strategies.

Transforming growth factor-β (TGFβ) has a well-established role in malignancy and its inhibition has demonstrated strong preclinical activity. However, TGFβ blockade has repeatedly failed in clinical trials. Here, Barcellos-Hoff and Yom utilize human papillomavirus (HPV)-driven cancer as a model to explain these discrepancies and emphasize the need for refined strategies and understanding of TGFβ signalling to enhance therapeutic efficacy.

In this Perspective, Joshua Rubin emphasizes the importance of gender–sex interaction (GSI) differences in cancer biology and clinical parameters to enhance precision medicine. He outlines the challenges and opportunities of integrating GSI effects into personalized oncology and argues that optimal outcomes require extending our current molecular approaches to include family history, life history and individual vulnerabilities in our diverse groups of patients with cancer.

In this Perspective, Kamila Naxerova discusses how genetic analyses of primary tumours and matched metastases can distinguish between competing metastasis evolution models, arguing that further insights into human metastasis biology could be enabled by a framework that rigorously quantifies whether metastases descend from a nonrandom selection of primary tumour lineages.