Issues

This consortium study defined distinct somatic cancer gene mutation patterns by race/ethnicity and sex among patients with early-onset colorectal cancer (CRC), yielding novel biological clues into early-onset CRC disparities.

CD19/CD20 bispecific CAR-T cells enriched in naive and memory phenotypes achieve robust antitumor efficacy and durability of response with minimal toxicity in patients with relapsed and refractory non-Hodgkin lymphoma.

NVL-520, a selective macrocyclic inhibitor of ROS1, demonstrated antitumor activity in patient case studies of ROS1 inhibitor–refractory lung cancers without observed neurologic toxicities attributed to TRK inhibition.

A machine learning model using multifeature fragmentome data from genome-wide cell-free DNA analyses detected hepatocellular carcinoma with high sensitivity and specificity in average and high-risk populations, including in early-stage disease.

New methods for the analysis of circulating tumor DNA from patient-derived xenograft plasma inform on tumor gene regulation and provide a blood-based signature for classifying prostate cancer phenotypes in clinical patient samples.

Multiomic profiling of malignant peripheral nerve sheath tumors reveals genomic events that underlie tumor evolution including extensive somatic copy-number alterations (SCNA), with detection of specific SCNAs in cell-free DNA being able to predict prognosis.

The computational tool BipotentR was used to reveal drug targets that can inhibit tumor growth by concurrent immune activation and inhibition of a separate oncogenic pathway, leading to identification of ESRRA as a top immune–metabolic target.

LZTR1 mutations stabilize and activate EGFR and AXL proteins in cancer, thus conferring specific vulnerability of LZTR1-mutant cancers to combination treatment with EGFR and AXL inhibitors.

Mutant NPM1 in leukemia obtains neomorphic activity to hijack active HOXA/B and MEIS1 transcription on chromatin via the association of XPO1 and blocks the histone deacetylase activity associated with myeloid differentiation.

NPM1c is recruited to self-renewal–associated genes and enhances their transcription in cooperation with the MLL histone methyltransferase complex, which can be targeted by Menin–MLL inhibitors.

The survival of a subset of carcinoma cells is dependent on the function of the BIRC6 ubiquitin ligase complex, which prevents aberrant activation of the integrated stress response via degradation of the HRI kinase.