Wistar, Temple Scientists Identify Drug Combo That Cuts Ovarian Tumors in Mice by Targeting TMLHE
Updated
Updated · Newswise · May 27
Wistar, Temple Scientists Identify Drug Combo That Cuts Ovarian Tumors in Mice by Targeting TMLHE
1 articles · Updated · Newswise · May 27
Nature-published findings show mildronate plus cisplatin reduced ovarian tumor burden in mouse models, while either drug alone produced no significant effect.
The team traced chemo resistance to a newly described pathway in which accumulated αKG activates TMLHE, boosts carnitine synthesis and enables histone acetylation that lets cancer cells repair DNA damage.
Blocking TMLHE or carnitine synthesis prevented repair machinery from assembling and made DNA repair-proficient ovarian cancer cells markedly more sensitive to platinum chemotherapy.
Patient data linked high TMLHE expression to worse progression-free survival after chemotherapy, while elevated serum acetylcarnitine at diagnosis independently tracked faster disease progression.
The researchers said a blood test for acetylcarnitine could help identify patients likely to resist platinum treatment, and the αKG-acetylation mechanism may also matter in other cancers and aging.
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Targeting Metabolic Vulnerabilities: Mildronate and the αKG–Carnitine Pathway Offer New Hope Against Ovarian Cancer Resistance
Overview
A major breakthrough announced by The Wistar Institute and Temple University reveals a new way to fight chemotherapy-resistant ovarian cancer. Researchers discovered that blocking the αKG-mediated carnitine synthesis pathway in cancer cells causes them to lose important histone acetylation marks and weakens their ability to repair DNA damage. This makes the cancer cells much more vulnerable to treatments that cause DNA injury. The findings, published in Nature, highlight a critical metabolic weakness in resistant ovarian tumors and open new possibilities for making existing therapies more effective.