Volume 1 Issue 6, June 2020

The COVID-19 pandemic has disrupted the spectrum of cancer care, including delaying diagnoses and treatment and halting clinical trials. In response, healthcare systems are rapidly reorganizing cancer services to ensure that patients continue to receive essential care while minimizing exposure to SARS-CoV-2 infection.

The risks posed to patients with cancer by the current COVID-19 pandemic demand rapid structural changes in healthcare delivery, with many positive changes likely to continue long term. An immediate critical reassessment of trial methodology based on clinical and scientific priorities is essential to ensure the resilience of clinical cancer research and optimize patient-centered care.

KEAP1 is a tumor suppressor encoded by a gene commonly mutated in lung cancer. A systematic search for Keap1-mutant cancer vulnerabilities now reveals that Slc33a1 is a context-specific essential gene that represents a promising new anti-cancer target.

The pre-metastatic niche is a complex microenvironment formed by the influence of tumor-derived factors on stromal and immune cells at distant sites of disseminated tumor-cell colonization. Signaling through the kinase p38α and regulation of the type I interferon receptor are now linked to formation of the pre-metastatic niche.

Bozic and Wu discuss how quantitative mathematical models elucidate the various stages of tumor evolution, from premalignancy to malignant progression, and the response to therapy.

A druggable genome CRISPR-Cas9 screen followed by functional validation in preclinical lung cancer models uncovers Slc33a1 as a Keap1-mutant-specific targetable dependency.

Gui et al. report that tumor-cell-derived factors induce p38a activation in lung fibroblasts, leading to inactivation of type I interferon signaling, matrix remodeling and neutrophil infiltration, thereby generating a metastasis-permissive niche.

Van Loo and colleagues report that loss of the Zeb2 regulator of epithelial-to-mesenchymal transition from the intestinal epithelium leads to inflammation, increased intestinal permeability and colorectal cancer development, which is enhanced by the resident intestinal microbiome.

Alkallas et al. uncover new significantly mutated genes in a large cohort of cutaneous melanoma, including the RNA helicase DDX3X, through integrated analysis of genomic, transcriptomic and DNA methylation data.

Parsa et al. report a mechanism of lymphoma initiation involving cooperation of BCL2 and increased activity of the metabolic enzyme SHMT2, which imparts changes in DNA and histone methylation.