HER3 + TROP2

Class

bispecific antibody-drug conjugate

Pathway

dual-antigen engagement of HER3 and TROP2 with cytotoxic payload delivery to tumor cells expressing either target

HER3 and TROP2 are two cell-surface proteins frequently overexpressed on epithelial tumors. HER3 (also called ERBB3) is a receptor of the EGFR family that, upon partnering with other family members, activates intracellular growth and survival signaling. TROP2 is a transmembrane glycoprotein involved in calcium-dependent signaling and cell proliferation, also enriched on many solid tumor cells relative to normal tissue. A bispecific antibody-drug conjugate (ADC) directed at both targets combines a single antibody scaffold capable of binding either antigen with a potent cytotoxic payload attached through a chemical linker. When the antibody engages either HER3 or TROP2 on a tumor cell, the complex is internalized and the payload is released inside the cell, causing damage that leads to cell death. Designing the molecule to recognize two antigens rather than one addresses a common problem in solid tumors: antigen expression is often heterogeneous, so a proportion of cancer cells may express only one of the two markers. A dual-targeting ADC can still engage and kill such cells, broadening the population of tumor cells addressed compared with an ADC built against a single antigen. This class of mechanism is being explored across carcinomas where HER3 and TROP2 are commonly co-expressed, including breast, lung, and other epithelial cancers.