MAPK signaling reprogramming via integrative TCM-Western medicine strategy: mechanistic interactions between bioactive herbal components and chemotherapy in ovarian cancer therapy - a comprehensive review.

Ovarian cancer (OC) ranks as the sixth leading cause of cancer-related mortality among women globally, with a five-year survival rate below 50%. These malignancies may originate from the ovarian surface epithelium, gonadal stroma, or germ cells, where the central therapeutic challenge lies in the development of chemoresistance. Traditional Chinese medicine (TCM) demonstrates unique advantages in enhancing chemosensitivity, arresting cell cycle progression, suppressing proliferation, inducing apoptosis, inhibiting angiogenesis, mitigating chemotherapeutic adverse effects, and improving postoperative quality of life. The mitogen-activated protein kinase (MAPK) signaling network—comprising ERK, p38, and JNK pathways—orchestrates cellular proliferation, death, and microenvironment remodeling through a three-tiered kinase cascade (MAPKKK→MAPKK→MAPK). Its aberrant activation forms bidirectional regulatory circuits with tumor-adaptive signaling network rewiring, driving platinum resistance. Although conventional chemotherapy transiently inhibits core MAPK nodes (e.g., ERK phosphorylation), it fails to block compensatory bypass mechanisms such as PI3K/WNT pathways. Through systematic interrogation of PubMed, Embase, Web of Science, and CNKI databases, this study proposes a dual-mode synergistic strategy termed “pathway targeting-dynamic network remodeling.” This approach deciphers the efficacy-enhancing mechanisms of integrated TCM-Western therapy from spatiotemporal signaling dynamics, establishing a theoretical framework for developing precision combination therapies guided by network pharmacology and computational modeling.