Volume 1 Issue 2, February 2020

By integrating discovery science with clinical practice and therapeutic intervention, clinician-scientists fulfil a unique role in cancer research. However, their numbers are in decline, which is creating the need for flexible training and research opportunities to ensure their future.

Low- and middle-income countries share the greatest burden of cancer mortality globally but lag behind high-income countries in terms of clinical trials. Here we discuss the challenges facing low- and middle-income countries and the opportunities for conducting trials of affordable, accessible and effective interventions relevant to the local population.

Zena Werb is Professor and Vice Chair of the Department of Anatomy at the University of California at San Francisco and Associate Director for Basic Science of the UCSF Helen Diller Family Comprehensive Cancer Center. Nature Cancer caught up with her at the 6th International Conference on Tumor Microenvironment and Cellular Stress organized by Aegean Conferences and held in Greece in the fall of 2019, to talk about her career and work in the tumor microenvironment field.

Filtered through the analytical power of artificial intelligence, the wealth of available biomedical data promises to revolutionize cancer research, diagnosis and care. In this Viewpoint, six experts discuss some of the challenges, exciting developments and future questions arising at the interface of machine learning and oncology.

Drug repurposing is an attractive strategy for extending the arsenal of oncology therapies. Screening of a large collection of existing non-oncology compounds against a panel of cancer cell lines now identifies several drugs capable of selectively inhibiting the growth of cancer cells.

Tumor heterogeneity remains an obstacle to effective clinical management of breast cancer. Two new studies use high-dimensional imaging of single-cell protein expression in situ in clinical samples to link genomic alterations to multi-cellular features of the tumor microenvironment and reveal breast-cancer phenotypes associated with clinical outcome.

Discerning and analyzing the mutational patterns that arise in the cancer genome can provide essential information on the process of tumorigenesis. An analytical framework and web-based tool now aim to aid in mutational signature assignment for improved tumor stratification.

Identifying indicators of response to immunotherapy is key for treatment decisions. Two studies now report that early changes in T cell repertoires and CD8⁺ memory effector cytotoxic T cells in peripheral blood correlate with response to immune-checkpoint inhibitors in metastatic melanoma and may serve as actionable biomarkers of immune activation.

Bodenmiller and colleagues pair imaging mass cytometry with data from the METABRIC cohort to define single-cell phenotypic and genomic features of breast cancer with spatial context, finding associations with breast cancer subtypes and prognosis.

Diehn and colleagues report that assaying circulating DNA in patients receiving chemoradiation therapy for non-small-cell lung cancer could identify the patients most likely to benefit from consolidation immunotherapy.

Li and colleagues report that extracellular cGAMP produced by cancer cells acts as an immunotransmitter that, when combined with ionizing radiation, can reduce tumor volume.

Kupper and colleagues introduce the T-cell fraction as a molecular assessment of T-cell-mediated antitumor responses in primary melanomas that can predict metastatic recurrence.

Marais and colleagues report that checkpoint inhibitor treatment of patients with melanoma leads to dynamic changes in peripheral T cells and expansion of immune effector cells. This awakening of the immune system occurs early after treatment and could be exploited in the clinic.

Cong et al. show that MTSS1 suppresses breast cancer initiation by promoting ubiquitin-mediated suppression of the NF-κB pathway. Loss of this regulatory mechanism promotes the activation and expansion of tumor-initiating cells.

Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.

Degasperi et al. introduce a practical framework and Signal, an online tool, to analyze mutational signatures. They find evidence of tissue-specific variability in mutational signatures, which may impact tumor classification and clinical application.