The Role of Traditional Chinese Medicine in the Management of Polyploid Giant Cancer Cells

Cancer causes millions of deaths globally every year. At its later stages, cancers are primarily treated with systemic therapies which do not provide an effective cure; the remaining cancer cells ultimately acquire drug resistance, relapse, and metastasize. In particular, polyploid giant cancer cells (PGCCs), which arise in response to diverse cellular stressors such as therapeutic pressure, modulate the tumor microenvironment (TME) and immunity involved in cancer development. However, without the knowledge of well-established signaling cascades targeting PGCCs, the current treatment options for these cells remain limited. This review provides a summary of the latest research associated with PGCC formation and treatment outcomes in common metastatic cancers. In addition, we highlight how some traditional Chinese medicine (TCM) and their bioactive compounds may serve as prospective agents for arresting PGCCs through cell cycle regulation, cell death induction, and TME modulation. Specifically, we identify how these processes are closely associated with the initiation, self-renewal, and termination phases of the PGCC life cycle. Based on the principle in TCM of "strengthening vital qi to eliminate pathogenic factors," the most efficacious herbs for counteracting PGCCs have been identified as Coptis chinensis, Oldenlandia diffusa, Scutellaria baicalensis, Salvia miltiorrhiza, Curcuma longa, Astragali radix, and Panax ginseng. The bioactive compounds of these herbs include berberine, oleanolic acid, wogonin, tanshinone IIA, curcumin, Astragaloside IV, and ginsenoside Rh2. Given the multi-target characteristics of TCM, network pharmacology was performed to allow for an integrative approach to elucidating underlying mechanisms. In particular, TCM administration may modulate both the p53 signaling pathway and cell cycle-related proteins. This, in turn, alleviates PGCC-induced tumor recurrence and resistance. Collectively, this review emphasizes the central role of PGCCs in advanced cancer progression while strengthening the mechanistic insights of TCM in PGCC-oriented therapy.