Articles in 2025

Precision oncology knowledge bases provide cancer clinicians with a point-of-care interpretation of the therapeutic actionability of clinical genomic sequencing results. These knowledge bases are now positioned to expand beyond the annotation of individual somatic molecular alterations, however, important gaps remain. Here, Suehnholz and Chakravarty discuss key deficiencies in current precision oncology knowledge bases that present opportunities for the next generation of data annotation.

In this Tools of the Trade article, Simon Cleary describes the development of a new stabilization window for intravital imaging, which allows the visualization of leukocytes, cancer cells and fluid moving through living lungs.

In this World View, Emma J. Crosbie, leader of Team Womb, which was awarded the prestigious 2024 American Association for Cancer Research Team Science Award for work on Lynch syndrome-associated endometrial cancer, argues that cancer discovery and its clinical translation demands a team science approach.

The nervous and immune systems have co-evolved to respond to threats, including cancer. In this Review, Amit et al. outline the reciprocal interactions among neurons, immune cells and tumour cells that regulate peripheral antitumour immune responses and discuss how these mechanisms could be leveraged to enhance immunotherapy.

The efficacy of chimeric antigen receptor (CAR) T cell therapies in solid tumours is still limited by on-target, off-tumour toxicities. Now, Liu, He, Wang et al. engineered EchoBack-CAR T cells, an ultrasound activated, genetically modified CAR T cell that enables precise spatiotemporal activation.

Sharma et al. discovered that bone marrow osteolineage cells are producers of taurine in the leukaemia niche, which in turn drives leukaemia stem cell survival and self-renewal.

The 2025 annual meeting of the American Association for Cancer Research (AACR) was held under the theme ‘Unifying Cancer Science and Medicine: A Continuum of Innovation for Impact’. Here, we summarize some key highlights from the meeting.

This Review by Imianowski et al. outlines the various contributions that regulatory T cells, present in the tumour microenvironment, make towards tumour progression and highlight the ways in which they represent attractive next-generation immunotherapeutic targets.

Acquired therapeutic resistance is a key contributor to cancer treatment failure, requiring new approaches to address its complex mechanisms. In this Roadmap, Soragni, Knudsen and colleagues discuss the mechanisms of acquired resistance and the models to better study it. Finally, they promote integration of biomarker-driven strategies and cutting-edge technologies to advance predictive and proactive prevention in cancer therapy.

In this Review, Beringer and colleagues highlight how future strategies for developing immunotherapies using γδT cells and their receptors will depend on creating intentional imbalances between activating and inhibitory receptors through the genetic engineering of γδT cell-inspired biologics and cellular therapies.

Individuals of sexual and gender minorities (SGMs), particularly transgender and nonbinary individuals, face substantial disparities in cancer screening. Here, Davison et al. explore these challenges and call for inclusive healthcare practices and policies to ensure equitable access to cancer screening.

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.

Cancer prevention vaccines have reduced cancer-related mortalities, yet therapeutic cancer vaccine development and clinical translation continues to face challenges. Here, Zaidi, Jaffee and Yarchoan summarize the failures of cancer vaccines of the past, to highlight recent advancements in the field.

Melanoma exhibits distinct patterns of organ-specific spread. Now, Gurung et al. find that age-based variations in stromal lipid species dictate melanoma metastatic tropism to the liver.

In addition to its physical symptoms, cancer cachexia — a severe wasting syndrome — also leads to fatigue, apathy and depression. A recent study published in Science identifies neural circuit mechanisms that underlie these motivational symptoms.

In this Journal Club. Gupta and Das discuss a study demonstrating how Apc-deficient intestinal stem cells (ISCs) gain a competitive advantage over normal ISCs through the upregulation of NOTUM.

In this Tools of the Trade article, Xinyuan Bi describes the development of digital colloid-enhanced Raman spectroscopy (dCERS), a method that addresses the reproducibility issues of surface-enhanced Raman spectroscopy (SERS) at ultra-low concentrations by using single-molecule counting.