Volume 3 Issue 8, August 2022

Malignant pleural mesothelioma is a challenging disease with few approved treatments. Rapidly expanding insights into the pathogenesis of this cancer and clinical trials are now suggesting a variety of targeted and immune-oncology agents with the potential to address unmet clinical needs.

Structural variants (SVs), such as copy-number alterations, rearrangements and aneuploidies, are common somatic changes in cancer genomes and rich sources of driver oncogenes, but reconstructing these from sequencing data is a challenge. Two new studies shed light on the diversity and importance of the SV landscape in cancer.

Immune checkpoint inhibitors (ICIs) are effective for many cancers but can be limited by inflammatory toxicities. Little is known about how ICIs affect the reproductive system. New research in animal models with and without tumours demonstrates that ovarian reserves are depleted in mice treated with ICIs, which may influence fertility.

How pancreatic ductal adenocarcinoma persists despite limited nutrients within the tumor microenvironment warrants further investigation. A study now identifies a metabolic mechanism wherein NUFIP1 induces release of nucleosides from cancer-associated fibroblasts, leading to activation of MYC-dependent glucose consumption and tumor growth.

Brody and colleagues discuss the current status and potential of cancer vaccines, highlighting challenges and opportunities to advance promising candidates to the clinic.

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.

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.

Yuan et al. demonstrate that cancer-associated fibroblasts in the pancreatic tumor microenvironment secrete nucleosides through autophagy in an NUFIP1-dependent manner, thereby inducing glucose consumption under glutamine-deprived conditions and promoting tumor growth.

Langenau, Pinello and colleagues identify tumor-propagating stem cells in rhabdomyosarcoma that sustain tumorigenesis through integrated single-cell and functional characterization of patient-derived samples and preclinical models in vivo.

Mabe et al. find that GD2 levels correlate with lineage plasticity in neuroblastoma and identify ST8SIA1 as the key enzyme in GD2 synthesis. EZH2 inhibition in mesenchymal neuroblastoma cells elevates ST8SIA1, synergizing with anti-GD2 antibodies.

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.