This combination approach exerts synergistic anti-tumor effects through multiple mechanisms of action: (1) Temozolomide induces DNA replication stress and impairs damage repair pathways; (2) Neratinib blocks HER2-mediated oncogenic signaling through competitive receptor binding; (3) Enzalutamide suppresses androgen receptor signaling in prostate cancer; and (4) PARP inhibitors (Niraparib/Olaparib) induce synthetic lethality by compromising DNA repair capacity [111,167,168,169]. The gene discussed is AR; the disease is prostate carcinoma.