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New humanized mouse model provides insight into immunotherapy resistance

Credit: The Wistar Institute PHILADELPHIA (Jan. 12, 2021) Scientists at The Wistar Institute have created an advanced humanized immune system mouse model that allows them to examine resistance to immune checkpoint blockade therapies in melanoma. It has revealed a central role for mast cells. These findings were published today in the journal Nature Communications. Checkpoint inhibitors revolutionized therapeutic options for advanced melanoma. However, only a fraction of patients respond to this treatment and some relapse due to reemergence of therapy-resistant lesions. To better understand why some cancers do not respond or become resistant to checkpoint therapies, we need more preclinical models that mimic the human tumor immune environment, said Rajasekharan Somasundaram, Ph.D., a member of The Wistar Institute Melanoma Research Center, who is the first and corresponding author of the paper.

Markey Study Shows Kentucky Endometrial Cancer Patients Have Higher Rates of DACH1 Mutation

A new study by Markey researchers shows a higher-than-average rate of DACH1 mutations in Kentucky patients with endometrial cancer. LEXINGTON, Ky. (Jan. 12, 2020)  A new study by University of Kentucky Markey Cancer Center researchers shows that DACH1 mutations are prevalent in Kentucky patients with endometrial cancer, suggesting that DACH1 may be a candidate biomarker for future trials with immunotherapy. DACH1 is a transcriptional repressor and tumor suppressor gene that is frequently mutated in other cancers, including melanoma, bladder and prostate cancer. The loss of DACH1 expression is also associated with poor prognosis and reduced survival in women with uterine cancer. Published in PLOS One, the study sought to determine the frequency of DACH1 mutations in patients with endometrial cancer in Kentucky. Using the Oncology Research Information Exchange Network (ORIEN), a personalized medicine consortium that Markey joined in 2017, researchers examined clinical and genomic

Alternative cancer cell fuel source targeted as therapeutic approach for breast cancer

 E-Mail IMAGE: Wistar scientists characterized an inhibitor that targets acetate metabolism in cancer cells. This molecule caused tumor growth inhibition and regression in preclinical studies, demonstrating the promise of this approach as. view more  Credit: The Wistar Institute PHILADELPHIA (Jan. 7, 2021) Scientists at The Wistar Institute characterized an inhibitor that targets acetate metabolism in cancer cells. Cancer cells use acetate metabolism to support tumor growth in conditions of low nutrient and oxygen availability. This molecule caused tumor growth inhibition and regression in preclinical studies, demonstrating the promise of this approach as a novel therapeutic strategy for solid tumors. Study results were published today in

Wistar reports new class of antibiotics active against a wide range of bacteria

Credit: The Wistar Institute PHILADELPHIA (Dec. 23, 2020) Wistar Institute scientists have discovered a new class of compounds that uniquely combine direct antibiotic killing of pan drug-resistant bacterial pathogens with a simultaneous rapid immune response for combatting antimicrobial resistance (AMR). These finding were published today in Nature. The World Health Organization (WHO) has declared AMR as one of the top 10 global public health threats against humanity. It is estimated that by 2050, antibiotic-resistant infections could claim 10 million lives each year and impose a cumulative $100 trillion burden on the global economy. The list of bacteria that are becoming resistant to treatment with all available antibiotic options is growing and few new drugs are in the pipeline, creating a pressing need for new classes of antibiotics to prevent public health crises.

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