Abstract PO-016: Changes in the expression levels of DNAJAs in triple negative breast cancer cells exposed to cytotoxic chemotherapy

Abstract

Abstract Triple Negative Breast Cancer (TBNC) lacking biological targets results in limited therapeutic options and leads to high mortality rates. The last therapy is Doxorubicin (Cytotoxic chemotherapeutic drug), an anti-tumor therapeutic alternative; which has bad side effects (cardiotoxicity), due to dose dependence, leading to drug resistance. There are three primary mechanisms of action for doxorubicin: Intercalation into DNA, which directly affects transcription and replication. Inhibition of topoisomerase II activity during the double-strand break, which prevents the binding portion of the ligation reaction that topoisomerase II catalyzes, by stabilizing the DNA-topoisomerase II alpha complex. Lastly, generating free radicals as it cycles between its quinone and semi-quinone structures during metabolic reactions, which generates reactive oxygen species. Research says heat shock proteins (HSPs) help to protect cells using heat-shock response. Several HSPs have been tested, with limited knowledge of HSP40s (DNAJAs). We will determine which DNAJA (1 to 4) assists in the survival response to doxorubicin by observing the domains and expression of the proteins being exposed to chemotherapy. The J domain has shown to be a critical area for increasing cell sensitivity while reducing cardiotoxicity. Expression levels were analyzed via RT-PCR and Western Blots, and relevant domains via COSMIC database. In conclusion the first step to reducing cardiotoxicity with chemotherapeutics is by modifying HSP40 functionality in human cancer cells, providing an alternative to hypersensitization to chemotherapy, allowing for lower dosage with less side effects. Citation Format: Devon Freeny. Changes in the expression levels of DNAJAs in triple negative breast cancer cells exposed to cytotoxic chemotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-016.