One Year of Nature Cancer

This month marks one year since the launch of Nature Cancer. As we celebrate our first anniversary, we reflect on the past year and thank the cancer research community for embracing our journal.

Inhibition of the anti-apoptotic protein BCL-2 has emerged as a highly effective treatment for acute myeloid leukemia; approved lower-intensity venetoclax combination therapies are now being rapidly incorporated into an improved standard of care for this cancer. Here we recount an abbreviated history of venetoclax for acute myeloid leukemia, focusing on a selection of key studies along the path from development into the clinic.

Recent preclinical and clinical research has led to exciting advances related to high-grade serous ovarian cancer, from examining its cellular origins to gaining insight into DNA-damage-repair mechanisms that may be leveraged for therapies. Furthermore, studies have demonstrated clinical benefit for inhibition of the polymerase PARP and modulation of the cell cycle, and have identified molecular features related to therapeutic response.

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.

Beltran and colleagues discuss the challenges in treating metastatic prostate cancer and strategies to accelerate precision oncology and improve therapy and clinical decisions in this setting.

Wu et al. develop trispecific antibodies that recognize CD38, CD3 and CD28 and induce T cell activation and co-signaling. They show in mice and non-human primates that by engaging multiple targets, these antibodies induce enhanced tumor-cell killing.

Golub and colleagues tested thousands of drugs not originally developed for oncology across 578 human cancer cell lines, revealing growth-inhibitory effects and providing a resource to identify drugs with the potential to be repurposed for cancer.

Chandarlapaty and colleagues use longitudinal ctDNA samples to identify genomic alterations in PTEN and ESR1 associated with resistance in a phase I/II trial of a PI3K inhibitor and aromatase inhibition for hormone receptor–positive metastatic breast cancer.

Siu and colleagues use a bespoke ctDNA assay and show predictive utility of longitudinal ctDNA analysis in a phase II clinical trial of patients receiving pembrolizumab that included multiple solid tumor types.

Barlesi and colleagues describe the determinants of severe COVID-19 outcomes in patients with cancer managed at the Gustave Roussy Cancer Centre.

The authors identify a population of L1CAM-positive cells that, following loss of epithelial integrity, promote intestinal tissue regeneration and mediate metastasis initiation and chemoresistance in colorectal cancer.

Li and colleagues report that extracellular cGAMP produced by cancer cells acts as an immunotransmitter that, when combined with ionizing radiation, can reduce tumor volume.

Mellman and colleagues show that dendritic cells represent a key source of PD-L1 in the tumor microenvironment, thereby restricting tumor infiltration by CD8⁺ T cells and antitumor responses.

Smith et al. report that age-associated mutations in mitochondrial DNA cause defects in oxidative phosphorylation. This results in metabolic rewiring, which subsequently contributes to accelerated development of colorectal cancer.

Scherz-Shouval and colleagues characterize the dynamic changes in cancer-associated fibroblast subpopulations during breast cancer progression. They find that the ratio of S100A4⁺ and PDPN⁺ CAF subsets is associated with clinical outcome.

Marra and colleagues describe POG570, a pan-cancer, whole-genome, transcriptome and clinical dataset stressing the molecular interactions in advanced and post-therapy cancer patients.

Anagnostou et al. present an improved predictor of response to immune checkpoint blockade that integrates estimates of tumor mutational burden corrected for tumor purity, RTK genomic alterations, a smoking-related mutational signature and HLA status.

Two papers by Kather and colleagues and Gerstung and colleagues develop workflows to predict a wide range of molecular alterations from pan-cancer digital pathology slides.

Two papers by Kather and colleagues and Gerstung and colleagues develop workflows to predict a wide range of molecular alterations from pan-cancer digital pathology slides.

Using single-cell RNA sequencing, CyTOF and multiplex immunohistochemistry, Steele et al. survey the immune landscape in pancreatic cancers, adjacent tissue and blood, observing heterogeneous immune checkpoint receptor expression within patients.