Study suggests a new way to personalize anti-CTLA-4 therapy for cancers
A Ludwig Cancer Research study has identified a novel mechanism by which a type of cancer immunotherapy known as CTLA-4 blockade can disable suppressive immune cells to aid the destruction of certain tumors. The tumors in question are relatively less reliant on burning sugar through a biochemical process known as glycolysis.
Researchers led by Taha Merghoub and Jedd Wolchok of the Ludwig Center at Memorial Sloan Kettering Cancer Center (MSK) and former postdoc Roberta Zappasodi-;now at Weill Cornell Medicine-;have discovered that in a mouse model of glycolysis-deficient tumors, CTLA-4 blockade does much more than stimulate cancer-targeting T cells of the immune system.
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Ludwig Cancer Research study reveals how certain gut bacteria compromise radiotherapy
A study led by Ludwig Chicago Co-director Ralph Weichselbaum and Yang-Xin Fu of the University of Texas Southwestern Medical Center has shown how bacteria in the gut can dull the efficacy of radiotherapy, a treatment received by about half of all cancer patients. Their findings appear in the current issue of the Journal of Experimental Medicine.
“Our study identifies two families of gut bacteria that interfere with radiotherapy in mice and describes the mechanism by which a metabolite they produce-a short chain fatty acid called butyrate-undermines the therapy,” said Weichselbaum.
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Cancer cells are known for spreading genetic chaos. As cancer cells divide, DNA segments and even whole chromosomes can be duplicated, mutated, or lost altogether. This is called chromosomal instability, and scientists at Memorial Sloan Kettering have learned that it is associated with cancer s aggressiveness. The more unstable chromosomes are, the more likely that bits of DNA from these chromosomes will end up where they don t belong: outside of a cell s central nucleus and floating in the cytoplasm.
Cells interpret these rogue bits of DNA as evidence of viral invaders, which sets off their internal alarm bells and leads to inflammation. Immune cells travel to the site of the tumor and churn out defensive chemicals. A mystery has been why this immune reaction, triggered by the cancer cells, does not spell their downfall.
Researchers led by Ludwig San Diego Member Don Cleveland and Peter Campbell of the Sanger Center have solved the mystery of how free-floating circular DNA fragments, which are almost exclusively found in cancer cells, drive gene amplification to generate drug resistance in cancer.
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Ludwig Cancer Research study reveals how circular ecDNA is generated and drives drug resistance in cancer
Researchers led by Ludwig San Diego Member Don Cleveland and Peter Campbell of the Sanger Center have solved the mystery of how free-floating circular DNA fragments, which are almost exclusively found in cancer cells, drive gene amplification to generate drug resistance in cancer. The research, published on December 23 in the journal Nature, provides new insights into how cancers evolve to adapt to changing environments and suggests ways to reduce drug resistance by combining therapies.
“Drug resistance is the most problematic part of cancer therapy,” said Ofer Shoshani, a postdoctoral researcher in Cleveland’s lab and the study’s first author. “If not for drug resistance, many cancer patients would survive.”