image: Following intravenous administration, ADCs circulate in the bloodstream (①) and specifically bind to their target antigen on the tumor cell surface (②). The antigen–ADC complex undergoes receptor-mediated endocytosis (③), after which the conjugate is trafficked into endolysosomal compartments, where proteolytic cleavage or linker degradation occurs to release the cytotoxic payload (④). The liberated payload exerts diverse effector functions (⑤), including inhibition of microtubule polymerization, induction of DNA damage, disruption of energy metabolism, and in some cases phototoxicity upon irradiation, ultimately leading to tumor cell death.
Credit: ©Science China Press
Gynecological cancers, primarily cervical, ovarian, and uterine cancer, continue to be a significant threat to women's health worldwide. While surgery and chemotherapy are the current standard treatment, patients often face challenges including high recurrence rates, severe side effects, and poor prognoses. Therefore, there is an urgent need to identify effective targeted treatment approaches. Antibody-Drug Conjugates (ADCs) have emerged as potent anti-tumor agents, leading to breakthroughs in the treatment of diverse solid tumors, including cervical and ovarian cancer. Currently, two ADCs have been approved by the FDA for gynecological cancer.
ADCs consist of three components: an antibody, a payload, and a linker. They work by using the targeted antibody to deliver the cytotoxic payload directly into cancer cells. Once inside, the drug is released, destroying the tumor cell from within while minimizing damage to healthy cells.
The accelerated approval of the first ADC, tisotumab vedotin, for recurrent or metastatic cervical cancer in 2021 marked a new era in the treatment of gynecological malignancies. Since then, global research has accelerated, with numerous ADC drugs now in clinical trials for various gynecological cancers. Antigens of ADCs in gynecological cancer include FRα，HER2, TF, Trop2, mesothelin, B7-H4, CDH-6, NaPi2b, and others. The ADCs under clinical and preclinical investigation offering new prospects for patients who have exhausted traditional treatment options.
Experts note that while ADCs come with their own unique profile of side effects that need careful management, they will become more personalized and precise in the future, bringing further hope to patients.
Journal
Science China Life Sciences
Method of Research
Literature review