Walle & Bajaj et al. assess the frequency of cytokine release syndrome upon COVID-19 vaccination in patients with cancer receiving immune-checkpoint inhibitors and find that while elevated cytokines levels are common, they do not manifest in detectable CRS.

Winter and colleagues demonstrate that metabolic adaptation to nutrient stress in the tumor microenvironment of pancreatic cancer leads to a dependency on IDH1, which is therapeutically actionable regardless of IDH1 mutation status.

Raj and colleagues show that ERX-41 inhibits lipase-independent functions of LIPA and induces ER stress in different tumor types, providing a therapeutic strategy in PDX models of pancreas, ovarian and triple-negative breast cancer.

Stanley and Abdel-Wahab review the latest insights into the biological mechanisms of RNA splicing dysregulation in cancer and the emerging landscape of therapeutic opportunities in this field.

Hata and colleagues identify lorlatinib analogs that overcome acquired therapy resistance to current ALK inhibitors and show their efficacy in preclinical models of non-small cell lung cancer bearing compound therapy-resistant ALK alterations.

Walle & Bajaj et al. assess the frequency of cytokine release syndrome upon COVID-19 vaccination in patients with cancer receiving immune-checkpoint inhibitors and find that while elevated cytokines levels are common, they do not manifest in detectable CRS.

Winter and colleagues demonstrate that metabolic adaptation to nutrient stress in the tumor microenvironment of pancreatic cancer leads to a dependency on IDH1, which is therapeutically actionable regardless of IDH1 mutation status.

Skokos and colleagues characterize human early-stage clear cell renal cell carcinoma with single-cell ATAC-seq and RNA-seq, identifying a spectrum of NFκB-promoted T cell dysfunction in the microenvironment and defining a pro-apoptotic signature.

Wood and colleagues report that the XPO1 inhibitor selinexor activates PI3Ky-dependent AKT signaling in AML via upregulation of P2RY2 and demonstrate a synergistic effect of combining selinexor with inhibition of prosurvival AKT signaling.

Raj and colleagues show that ERX-41 inhibits lipase-independent functions of LIPA and induces ER stress in different tumor types, providing a therapeutic strategy in PDX models of pancreas, ovarian and triple-negative breast cancer.

As guidelines, therapies and literature on cancer variants expand, the lack of consensus variant interpretations impedes clinical applications. CIViC is a public-domain, crowd-sourced and adaptable knowledgebase of evidence for the clinical interpretation of variants in cancer, designed to reduce barriers to knowledge sharing and alleviate the variant-interpretation bottleneck.

Nature Cancer and the Nature journals are raising the standards on reporting on sex and gender in research. Starting this June, authors will be prompted to provide details on how sex and gender were considered in study design.

The advent of EGFR inhibitors has been a game changer in clinical oncology. However, differing sensitivity to different mutations, resistance and adverse effects continue to impede decisive treatment of mutant EGFR–driven cancers, which highlights the need for advanced and innovative EGFR-targeting approaches.

A deeper understanding of the specific tumor context and microenvironment, the underlying tumor immunology, and barriers to effective treatment, including therapy resistance and adverse effects, is essential to the development of improved immunotherapy modalities and regimens.

Robust and faithful preclinical models are essential for understanding the underlying biology of human cancer and for devising new and improved therapies.

A deeper understanding of the molecular and cellular underpinnings of metastatic disease and a renewed focus on metastasis-targeting therapeutic approaches raise hopes for improved clinical translation.