Researchers identified a new role for heat shock protein 90 (HSP90) in cancer predisposition and treatment resistance. HSP90 buffers BRCA1 mutations, masking their negative effects and delaying breast cancer onset. This buffering creates a vulnerability in cancer cells, revealing a potential therapeutic strategy in which targeting HSP90 could be used to overcome treatment resistance. The study, led by Georgios Karras, Ph.D., associate professor of Genetics, identifies predictive features of HSP90 buffering in patients with specific mutations in BRCA1 that may help...

Researchers showed that a specific subset of mutations in the POLE gene is strongly associated with durable responses to immunotherapy in patients with metastatic colorectal cancer (CRC). This type of mutation, called loss-of-proofreading (LOP) mutations, affects specific functions of the POLE protein. The study, led by John Paul Shen, M.D., assistant professor in Gastrointestinal Medical Oncology, and Giulia Maddalena, M.D., Ph.D., former graduate student and attending physician, aimed to help identify and predict which patients benefit from immune checkpoint therapy, avoiding potentially...

Cancer cells can break down the protective covers around nerves, causing nerve injury that triggers chronic inflammation leading to immune exhaustion and eventual resistance to immunotherapy, according to new research from The University of Texas MD Anderson Cancer Center.   The study underscores the importance of investigating interactions between cancer and the nervous system – a field known as cancer neuroscience. The results suggest that targeting the signaling pathways involved can reverse this inflammation and improve treatment responses....

In initial results from the AMPLIFY-201 trial, co-led by Shubham Pant, M.D., an immunotherapy vaccine targeting the lymph nodes showed potential in delaying relapse of KRAS-mutated pancreatic and colorectal cancers for patients who had previously undergone surgery. Long-term final follow-up data of this vaccine, ELI-002 2P, now shows that 17 of 25 patients (68%) had robust T cell responses, which were associated with increased survival. At 24 months, the median recurrence-free survival had not yet been reached for the higher response group – including all of...

The BRAF V600E gene mutation makes colorectal cancers (CRCs) more aggressive, leading to poorer survival rates. While some CRCs with high microsatellite instability respond well to immunotherapy, most BRAF V600E-mutant metastatic CRCs are microsatellite stable (MSS) and do not benefit from these treatments. The combination of encorafenib and cetuximab is Food and Drug Administration (FDA)-approved but has limited duration of response in these patients, which led Van Morris, M.D., and colleagues at MD Anderson to examine the safety and efficacy of adding the anti-PD-1...

Breast cancer often starts in the epithelial cells lining the milk ducts and lobules, but there are many subtypes that make it challenging to identify the cancer’s starting point within normal tissue. Researchers led by Nicholas Navin, Ph.D., developed a new single-cell DNA and RNA sequencing technology – called wellDR-seq – to identify ancestral breast cancer cells. By studying the impact of chromosome gains or losses on gene expression, the researchers were able to uncover the molecular...

Scientists often use organoids – laboratory-grown human cell culture systems that closely mimic body organs – to gain deeper insights into cancer biology and understand how tumors respond to drugs. Researchers led by Yuan-Hung Lo, Ph.D., used organoids along with several CRISPR gene editing tools to study how cisplatin chemotherapy interacts with different genes in the human stomach. The screens revealed an unexpected link between cisplatin sensitivity and fucosylation, a process that adds sugar molecules to cells. The researchers identified the TAF6L gene as a key regulator...

KRAS is the most commonly mutated gene in cancer, but targeting the mutant protein is notoriously difficult because current therapies work only for certain KRAS mutations. This led researchers Kathleen McAndrews, Ph.D., Anirban Maitra, M.B.B.S., Raghu Kalluri, M.D., Ph.D., and Timothy Heffernan, Ph.D., to examine the efficacy of a first-in-class inhibitor called BI-2493. This pan-KRAS inhibitor can target the mutant protein in multiple cancer types, regardless of the specific mutation present. BI-2493 was developed as part of the...

Natural killer (NK) cells became markedly better at killing cancer cells after scientists removed key gene targets identified through a new genome-wide CRISPR screening tool.   The study opens new avenues for discovering approaches to enhance the antitumor activity of chimeric antigen receptor (CAR) NK cell therapies against multiple cancer types via PreCiSE, a comprehensive CRISPR discovery platform optimized for primary human NK cells.   “Targeted gene editing is a powerful tool to enhance the...