UMIP-700 – Treatment of advanced breast cancer with LSD1/CoREST inhibitors

Problem: Breast cancer is the most commonly diagnosedtype of cancer in women, with the second highest mortality. Approximately 80% of breast tumors express the estrogenand progesterone receptors (ERa and PR). Agentstargeting the estrogen pathway represent the primary treatment modality whichcan be classified into three main categories: aromatase inhibitors (AIs),selective estrogen receptor modulators (SERMs), and degraders (SERDs). Despite the success of endocrine therapy, resistancearises in about 40% of cases (90,000 cases/year only in the US) after 5 yearsof treatment, leading to incurable metastatic disease. Metastatic breast canceris presently incurable. Most breast cancers express the estrogen receptor (ER)and agents targeting the estrogen pathway represent the main treatmentmodality. Therefore, there is a critical need to identify novel therapeutictargets to prevent and overcome metastatic endocrine resistant breast cancer.Importantly, endocrine resistant breast cancer is phenotypically very similarto triple negative breast cancer (TNBC), which is the most aggressivebreastcancer and currently patients have very limited options. Therefore, discoveryof novel molecular targets and therapeutic approaches to treat endocrineresistant breast cancer might also benefit patients with TNBC. Technology: Researchers at the University of Miami have developeda novel method for treatment of breast tumors. The method comprises thefollowing steps: 1) Determining expression of ER post endocrine treatment; 2)determining high expression of a set of 63 genes in breast cancer patientscompared to an individual without breast cancer or from adjacent normal tissueof the same individual with breast cancer; and 3) administering an effectiveamount of CoREST and/or LSD1 inhibitor to the patient. CoREST and/or LSD1inhibition upon chemo-endocrine therapies provides a method to bypassresistance in breast cancer patients. Peter Gutenberg pxg372@miami.edu 305-243-4604

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