Many patients with triple-negative breast cancer (TNBC) do not respond to combination treatment with chemotherapy and immunotherapy. Understanding what makes these tumors immunologically “cold,” or resistant to therapy, and how to turn them immunologically “hot,” could improve patient outcomes. Researchers led by Xi Chen, Ph.D., identified one such mechanism in which cancer cells can evade the immune system via an ancient stress sensor IRE1α activation, which blocks pathways that would normally ignite “cold” tumors and initiate an immune response. Using an...

A $3.3 million study at the University of Houston College of Optometry will track the health of patients with prediabetes and diabetes to find out who might develop eye problems and be at risk for future vision loss. The study is being led by Wendy Harrison, associate professor, and is underwritten by the National Eye Institute.   Vision loss in type 2 diabetes results from diabetic retinopathy, caused by damage to blood vessels in the retina,...

Many cancers rely on oncogenic transcription factors, which have been challenging to target with small molecule therapeutics. Inhibiting transcription with cyclin-dependent kinase 9 (CDK9) blockade has been investigated as an alternative. In a new study, Michael Green, Ph.D., and collaborators developed a way to relocate CDK9 using transcriptional/epigenetic chemical inducers of proximity (TCIPs), small molecules that bring two proteins together, to drive cell death pathways in B-cell lymphoma. They targeted the B-cell lymphoma 6 (BCL6)...

CD8+ T cells play a critical role in the immune system’s defense against cancer. In a study led by Sangeeta Goswami, M.D., Ph.D., researchers demonstrated that manipulating histone lactylation, an epigenetic modification to regulate gene expression, could improve the efficacy of CD8+ T cell responses in cancer therapies. Specifically, they analyzed the potential roles of H3K18la and H3K9la in CD8 T cells. The study demonstrated that, by targeting metabolic and epigenetic pathways to modulate H3K18la and H3K9la, it...

Brain metastases from breast cancer patients have elevated levels of Cdk5, which is typically found in neurons and is associated with poor outcomes. Researchers led by Dihua Yu, M.D., Ph.D., and Arseniy Yuzhalin, DPhil, examined how breast cancer cells spread to the brain and evade the immune system to develop. The researchers discovered that astrocytes, a type of cell in the brain, trigger the overproduction of Cdk5 in breast cancer cells metastasized to the brain, which reduces the expression...

Patients with metastatic colorectal cancer harboring BRAF-V600E mutations have poor prognoses, highlighting a need to identify biomarkers that can optimize treatment. The recent BEACON trial showed that the combination of encorafenib (BRAF inhibitor) and cetuximab (anti-EGFR antibody), with or without binimetinib (MEK inhibitor), improved overall survival, objective response rates and progression-free survival in pretreated patients compared to those receiving cetuximab with chemotherapy. In a follow-up analysis, researchers led by Scott Kopetz, M.D., Ph.D., performed genomic and transcriptional profiling on tumor tissue...