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Colloquium, Mayurika Mahendran, UWM Chemistry
March 13 @ 3:00 pm - 4:00 pm
Chemical Perspectives on Therapeutic Challenges and Emerging Treatment Strategies for Triple-Negative Breast Cancer (TNBC)
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous subtype of breast cancer characterized by the absence of Estrogen receptor (ER), Progesterone receptor (PR), and HER2 expression. TNBC accounts for approximately 15–20% of all breast cancers and is associated with early metastasis, high recurrence rates, and poor prognosis. Because TNBC lacks targetable hormone receptors, conventional chemotherapy remains the backbone of treatment. Common agents such as Paclitaxel, Doxorubicin, and Carboplatin exert their therapeutic effects through mechanisms including microtubule stabilization, DNA intercalation, Topoisomerase inhibition, and DNA crosslinking. Although these cytotoxic mechanisms are effective, systemic toxicity, chemo resistance, tumor heterogeneity, and radio resistance limit long-term therapeutic success.
Recent advances have expanded the TNBC treatment landscape through immunotherapy and targeted approaches. Immune checkpoint inhibitors, particularly PD-1/PD-L1 blockers such as Pembrolizumab, enhance T-cell–mediated tumor recognition and have demonstrated improved pathological complete response (pCR) and overall survival (OS) when combined with chemotherapy. Additionally, PARP inhibitors exploit synthetic lethality in BRCA-mutated TNBC by impairing DNA repair pathways, promoting tumor cell death.
Another promising strategy involves antibody-drug conjugates (ADCs), such as Sacituzumab Govitecan (SG), which combine monoclonal antibody specificity with potent cytotoxic payloads through cleavable linker chemistry, enabling selective intracellular drug release.
Combination therapeutic strategies are emerging as a critical direction in TNBC management. Integrating chemotherapy, immunotherapy, radiotherapy, and targeted agents has demonstrated improved progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) compared to monotherapy. From a chemical perspective, rational drug design, linker optimization, and molecular targeting strategies play central roles in improving selectivity, overcoming resistance mechanisms, and reducing systemic toxicity. Continued advancements in immunology, nanotechnology, and molecular biology are expected to facilitate personalized and more effective treatment strategies for TNBC.