Unveiling the antibody-drug conjugates portfolio in battling Triple-negative breast cancer: Therapeutic trends and Future horizon.

ABSTRACT

Triple-negative breast cancer (TNBC) showcases a labyrinthine network exhibiting deficient expression of Estrogen receptor (ER), Progesterone receptor (PR), and Human-epidermal growth factor receptor-2 (HER2). This restricts the conventional chemotherapeutic, hormonal, and few targeted regimens in showing efficient anti-tumor response. Antibody-drug conjugates (ADCs) are target-specific conjugates comprising a monoclonal antibody attached to the desired cytotoxic payload with the support of a stable linker. They are designated as one of the encouraging sets of targeted therapies that have unveiled affirmative outcomes owing to increased specificity in targeting the undetectable or deficiently expressed targets. Another virtue of ADCs lending superiority to this approach is the presence of inherent bystander effect which has a detrimental influence on the tumor microenvironment (TME) devoid of antigen expression. In the current scenario, FDA-approved Sacituzumab govitecan is widely being utilized to mitigate TNBC while many other ADCs are being studied in clinical trials. Additionally, a focus has been set on revelation of application of Trastuzumab deruxtecan in HER2-low metastatic breast cancer which widens the current therapeutic horizon dealing with such carcinomas. After making an effort towards sketching ADCs profile, we conclude that this novel approach deserves to be investigated through future campaigns owing to its remarkable bystander effect, ability to precisely recognize the antigen and spare the naïve cells from detrimental toxicity. Exploration of the remarkable potential of Sacituzumab govitecan in multiple indications including TNBC portrays the prominence of ADCs and prompts the bright future of this therapeutic approach. In this review, we present the basic foundation of ADCs alongside summarizing the building blocks of several ADCs used in TNBC. Furthermore, by shedding light on the therapeutic regimens and concomitant effects of various ADCs derived from the supportive backbone of clinical trials, we have attempted to convene several segments of ADCs and portray their potentialities time ahead.