Role of Thyroid Hormones in breast cancer resistance to chemotherapy

DIAZ ALBUJA JA; ROSEMBLIT, CINTHIA; DEBERNARDI, MERCEDES; CAYROL, FLORENCIA; STERLE, HELENA; PAULAZO, MARÍA ALEJANDRA; CREMASCHI, GRACIELA ALICIA; DIAZ FLAQUÉ C.

Simposio; Buenos Aires Breast Cancer Symposium (BA-BCS); 2021

Breast cancer (BC) is the leading cause of cancerdeath in women. Combination chemotherapy is one of theimportant adjuvant therapies for BC after surgery. Theefficacy of drug treatment is often limited by tumor cellresistance. Many BC acquire multidrug resistance (MDR)by upregulating the level or activity of membrane proteinssuch as Pgp, which enable the exclusion of cytotoxic substances from the intracellular environment. Previously wedemonstrated that Thyroid Hormones (TH) modulate chemotherapy response in T cell lymphoma (TCL). Howeverlittle is known about the modulation of TH in the mechanisms that lead to chemotherapy resistance in BC cells.Bexarotene (Bex) is an oral retinoid-X-receptor agonistthat is effective for the treatment in cutaneous TCL andthere are ongoing clinical trials studying its role for BCtreatment in combination with chemotherapeutic drugs.However thyroid dysfunction is recognized as an important side effect of Bex treatment, potentially manageable by TH administration. We found that Bex treatmentreduces intracellular drug accumulation in MDA MB 231cells, while TH revert this effect. Bioinformatics studiesrevealed alterations of genes significantly associated withdrug response and genes involved in the TH signalingpathways in paclitaxel resistant-BC cells vs paclitaxelresistant-BC cells treated with Bex. These results pointout the role of TH in BC resistance to chemotherapy andstrengthen the importance to check thyroid status duringBC therapy.