2022 in Review

Our ‘2022 in Review’ Focus highlights the year’s key developments in the cancer field in news articles, specially commissioned comment and opinion pieces, and an overview of the year’s most striking cancer research curated by the Nature Cancer editorial team.

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.

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.

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.

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.

Bernards and colleagues identify cFLIP as a common dependency of cancer cells by conferring protection from senolytic-induced cell death. They nominate combination of DR5 activation and cFLIP suppression for enhanced killing of senescent cancer cells.

Welm and colleagues present a biobank of human-derived xenografts and organoids and demonstrate its value for high-throughput drug screening and applied precision medicine.

Malanchi and colleagues demonstrate that irradiation in healthy lung tissue leads to an alveolar repair response orchestrated by neutrophils and Notch signaling that promotes metastatic colonization of disseminated tumor cells in the lung.

Alborzinia et al. report that MYCN-amplified neuroblastoma undergoes ferroptosis in the absence of intracellular cysteine, suggesting a combination of cysteine depletion and concomitant GPX4 inactivation as a potential therapeutic approach.

Hua and colleagues develop CAR T cells targeting CDH17 and show that they are effective at suppressing tumor growth in mouse and human models of neuroendocrine and gastrointestinal solid tumors, without damaging healthy tissues in preclinical models.

Jänne and colleagues discover and characterize an allosteric EGFR inhibitor with efficacy against therapy-resistant mutations and show preclinical efficacy as monotherapy and in combination in patient-derived xenograft models.

Amit and colleagues report that the specific interaction of a CD4⁺PD-1⁺CXCL13⁺ T-cell subset with antigen-presenting cells reprograms the tumor microenvironment and response to immune checkpoint inhibitors in non-small cell lung cancer.

Lim and colleagues present the UK PROSECO study where they assess humoral and cellular immune responses to one, two and three doses of vaccination against SARS-CoV-2 in patients with B-cell malignancies in a prospective observational study.

Danko and colleagues develop BayesPrism, a bulk RNA sequencing deconvolution tool to infer cell type composition and cell-specific expression levels across clinical cancer datasets.

Tamborero and colleagues develop the Molecular Tumor Board Portal, a virtual platform that integrates and interprets genomics and clinical data from prospective clinical studies, to support clinical decision-making for precision oncology.

Mu and colleagues describe a JAK–STAT signaling-dependent transition to a stem-like, multilineage state that is resistant to prostate cancer AR therapy and propose combinatorial targeting of JAK–STAT proteins to resensitize resistant tumors.

Isakoff and colleagues demonstrate the safety and feasibility, as well as the clinical efficacy, of neoadjuvant niraparib in a phase II study in patients with HER2-negative and BRCA-altered breast cancer.

Dubois and colleagues assemble a large cohort of human pediatric high-grade glioma samples, identifying patterns of simple and complex structural variants and characterizing their role in tumor development and evolution.

Zhang and colleagues analyze single-cell data from patients treated with immunotherapy in five cancer types and find that CXCL13-expressing subsets are implicated in response to treatment in the CD8⁺ and CD4⁺ T cell compartments.

Batlle and colleagues report that after chemotherapy, Mex3a⁺ colorectal cancer cells represent drug-tolerant persister cells that lead to recurrence by downregulating the WNT–Lgr5⁺ stem cell program and adopting a transient regenerative state.

Dive and colleagues develop an approach for genome-wide cell-free DNA methylation profiling, which can sensitively detect small cell lung cancer in liquid biopsy of patient samples, including stage I disease and molecularly defined SCLC subtypes.

In preclinical studies, Hutt, Loi and colleagues find that mice treated with checkpoint blockade have impaired ovarian function and reserve, associated with increased immune infiltrate, raising considerations about fertility implications for female patients.

Telli and colleagues present a phase II clinical trial of the PARP inhibitor talazoparib in patients with solid tumors and show that the drug has activity in patients with breast cancer with mutations in other homologous recombination pathway genes beyond BRCA1 and BRCA2.

Li et al. demonstrate mitochondrial fission in macrophages as key for phagocytosis induced by therapeutic antibodies. They identify overexpression of GFPT2 as an inhibitor of the process and phase transition of the phagocytic machinery as its regulator.

Shah and colleagues used machine learning to integrate features from computed tomography scan images, programmed death ligand-1 (PD-L1) immunohistochemistry and genomics into a multimodal predictor of response to anti-PD(L)1 in patients with NSCLC that outperformed single features such as tumor mutational burden.