Volume 2 Issue 12, December 2021

From a first-in-class KRAS approval to the latest agonist antibody failures, 2021 was another busy year for cancer drug developers.

Despite widespread vaccination, patients with cancer still face a slew of pandemic-related challenges.

Combination of approved immune checkpoint inhibitors has shown remarkable efficacy in the treatment of melanoma, but at the cost of high toxicity. After years of intensive research, inhibitors of the immune checkpoint molecule LAG-3 are now demonstrating promising results and favorable toxicity profiles in clinical trials in combination with inhibition of the checkpoint molecule PD-1.

The rapid progression of KRAS(G12C) inhibitors from preclinical characterization to the clinic has radically changed the perception of the KRAS oncogene as an undruggable target. Here we discuss ongoing and future possibilities for developing therapies using these inhibitors in clinical settings.

The COVID-19 pandemic has impacted cancer care globally, the consequences of which are still not well understood. Through the lens of the impact in India, we emphasize the importance of continuing cancer care even during extenuating public health circumstances, and of strengthening health systems as a global priority.

Recent advances in single-cell multiomics have provided holistic views of the multifaceted state of a cell and its interaction with the environment. The rapid development of these technologies has offered a unique opportunity to analyse the molecular and cellular heterogeneity in cancer, and could lead to better cancer diagnosis, treatment and prognosis.

Rapid progress in the molecular characterization of cancer genomes has been enabled by technology and computational analysis, and large databases now exist. Novel cancer therapeutics have resulted that more precisely target the vulnerabilities revealed by genomic analysis. Emergent efforts that link the two, using machine learning approaches and circulating DNA from cancer cells, are furthering cancer diagnosis and precision medicine.

Cancer multi-omics data has greatly expanded over recent decades, surpassing the human ability to extract meaningful information. The successful implementation of artificial intelligence systems into clinical pipelines to interpret complex datasets, and improve the outcomes of patients with cancer, demands strong validation using real-world evidence while also being mindful of ethical and social aspects.

Elisabete Weiderpass is an expert in cancer epidemiology and cancer prevention. She has been the Director of the International Agency for Research on Cancer, the specialized cancer agency of the World Health Organization, since January 2019. She spoke with Nature Cancer about 2021 and the years ahead.

50 years after the National Cancer Act was signed into law, Nature Cancer spoke with the National Cancer Institute Director Dr Ned Sharpless about the progress in cancer research and care, the complications of the pandemic and what to expect in the future.

Twelve early-career investigators share their thoughts on the challenges faced by their teams and communities during the past year, and look ahead to new opportunities for 2022.

Mutations arising from APOBEC3-induced cytidine deamination are often found in advanced human cancers, yet how APOBEC3 promotes tumor progression remains poorly understood. A new study finds that APOBEC3A drives chromosomal instability in a deaminase-domain-independent manner, thereby promoting STING-dependent cancer metastasis.

A genome-wide CRISPR screen finds CIP2A as a new synthetic lethal target for BRCA1- and BRCA2-deficient cells. Unlike PARP inhibition that increases replication-induced DNA double-strand breaks and radial chromosomes, depleting CIP2A or disrupting its interaction with TOPBP1 increases micronuclei and chromosomal missegregation, revealing a mitotic target for BRCA-mutated tumors.

Cancer is associated with higher risk of severe COVID-19 outcomes. Two studies prospectively analyze the immunological and clinical characteristics of a large cohort of patients with cancer following SARS-CoV-2 infection or vaccination, providing important clinical insights to improve the management of such vulnerable patients.

Despite the profound clinical success of immune-checkpoint inhibitors, their effectiveness is limited by intrinsic and acquired resistance. Bullman, Zitvogel and colleagues provide their views on two clinical trials modulating the microbiome of immunotherapy-resistant patients with melanoma via transplantation of fecal microbiota from patients who responded to immunotherapy.

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

Woermann and colleagues describe a deaminase-independent function for APOBEC3A in initiating chromosomal instability and STING-dependent metastasis in human and mouse pancreatic cancer.

Durocher and colleagues identify CIP2A through synthetic lethal CRISPR screens as a key regulator of adaptive feedback mechanisms controlling chromosomal stability arising from accumulated DNA lesions in BRCA-mutated tumor cells.

In two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy.

Peinado and colleagues show that small extracellular vesicles and secreted NGFR cargo induce lymphangiogenesis and develop the lymph node pre-metastatic niche to promote melanoma metastasis, which could be targeted pre-clinically with NGFR inhibition.

Zhang and colleagues perform systematic multiomics and functional integration of cell-surface proteins and develop a comprehensive catalog of cell-surface actionable targets across cancer, with a practical web platform to explore these data.