Volume 3 Issue 12, December 2022

From the first engineered T cell receptor medicine to regulatory snubs over China-only data, 2022 was another action-packed year for the oncology drug development community.

Three years after the pandemic began, COVID-19 is here to stay. Yet the effects of COVID-19 on cancer research are still unravelling.

Antibody–drug conjugates (ADCs) were first developed in the 1980s, and since then, technical advances have allowed their approval by the US Food and Drug Administration and their use in the treatment of various cancers. In 2022, several new ADCs were developed and tested in clinical trials, with promising results.

Tumors with DNA mismatch repair or proofreading deficiencies, either at the germinal or somatic level, usually present with high tumor mutational burden and often show striking responses to checkpoint blockade immunotherapy. Ongoing translational and clinical investigations of those tumor subsets provide avenues for further improvement in patient outcomes.

Recent progress indicates a considerably improved mechanistic understanding of CAR T cell biology and delivers important insights into why some patients achieve durable remissions and others do not. In addition, although most success has been achieved in the context of CAR T cells targeted to B cell tumor antigens, namely CD19 and BCMA, we are seeing promising clinical trial outcomes for solid tumor malignancies.

Liquid biopsies of circulating tumor DNA offer a non-invasive tool with many potential applications in oncology, including early cancer detection, profiling, disease prognosis, prediction of therapy response and monitoring disease status. A growing body of literature and clinical trials support an increasingly valuable role for liquid biopsies in the care of patients with solid malignancies.

Lisa M. Coussens is Professor and Chair of the Cell, Developmental and Cancer Biology department, and Deputy Director of Basic and Translational Research in the Knight Cancer Institute, at Oregon Health and Science University in Portland Oregon, USA. She is also President of the American Association for Cancer Research (AACR) for 2022–2023. Nature Cancer caught up with her to hear her thoughts on the past year and what’s in store for 2023.

Twelve early career investigators share experiences from the process of starting their laboratories throughout the past year, and reflect on the challenges faced and the opportunities seized.

The Nature Cancer editors share their thoughts on the highs (and some of the lows) of 2022.

Glioblastoma (GBM) brain tumor cells exhibit pronounced phenotypic plasticity, but exactly how this enables GBMs to inevitably resist standard treatment is not known. A new study uses multilevel molecular profiling of pre- and post-treatment human GBMs to shed light on treatment response with single-cell and spatial resolution.

Pancreatic ductal cells transport bicarbonate from blood to pancreatic juice. A study shows that pancreatic cancer retains SLC4A4-mediated bicarbonate import to fuel cancer growth via enhanced glycolysis and establish a pro-tumorigenic immune microenvironment. Targeting SLC4A4 mitigates acidosis and can be combined with checkpoint blockade.

Samson and Ablasser review the roles of the cGAS–STING pathway in cancer and efforts to target this signaling axis therapeutically.

Mazzone and colleagues identify the bicarbonate transporter SLC4A4 as highly abundant in epithelial duct cells in pancreatic cancer and show that its inhibition mitigates acidosis in the tumor, thereby alleviating immune suppression and overcoming immunotherapy resistance.

Earnest-Noble et al. report the opposing regulation during breast cancer metastasis of two isoleucyl tRNAs that decode synonymous codons, leading to divergent regulation of metastatic growth by influencing translation of growth-regulating genes.

Spurr et al. identify high pretreatment aneuploidy score as a potential biomarker in patients with NSCLC who benefit from concurrent radiation and immune checkpoint inhibition, in immunogenomic analysis of data from a phase I clinical trial.

Shahbandi et al. find that cancer cells that survive chemotherapy (CT) activate two immune-modulatory programs characterized by IFN response genes and CD274 or p53 signaling and CD80 expression. Targeting these pathways enhances the CT response.

Wang et. al. perform single-cell and spatial analyses of paired primary and recurrent samples from patients receiving standard-of-care therapy for GBM and find changes in tumor signaling pathways and the microenvironment with targetable potential.