Neo-endocrinochemotherapy: a novel approach for enhancing chemotherapeutic efficacy in clinic?

ABSTRACT

Chemosensitization means enhancing the sensitivity of tumor cells to chemotherapy with certain methods for better efficacy. Tumor progression depends on stimulation of multiple hormones, decrease in hormones during chemotherapy induces G0/G1 arrest of tumor cells, which may be the main cause for chemoresistance. Some of the choriocarcinoma and testicular tumors are curable with chemotherapy only, underlying mechanism may refer high level of human chorionic gonadotropin, which has thyroid stimulating hormone like effect and even induce hyperthyroidism in these patients. Some of these patients usually have high levels of thyroid hormones or suffer thyroid crisis during chemotherapy. Possibly owning to the proliferative or metabolic promotion effect of thyroid hormones and/or other endocrine hormones, which can promote tumor cells in G0 phase metabolizing actively or stepping into division cycle again, tumors are more sensitive to chemotherapy. Both endocrinotherapy and chemotherapy are major therapies for tumor, traditional endocrinotherapy suppresses tumor progression through decreasing tumor-dependent hormones or competitively combining and blocking hormone receptors. While, chemotherapy mostly killed tumor cells that proliferate actively, because tumor cells retardant in G0 phase by endocrinotherapy are no more sensitive to chemotherapy, endocrinotherapy cannot be concurrently used with chemotherapy. Nevertheless, decrease in hormones during chemotherapy is similar to concurrently using endocrinotherapy and chemotherapy. It has been found in some basic researches that some chemotherapeutics concurrently combined with endocrine hormones can achieve better efficacy compared with chemotherapy only. It is therefore hypothesized in this article that decrease in hormones during chemotherapy causes cell cycle arrest and renders tumor cells insensitive to chemotherapy; addition of endocrine hormones to mimic the hormones and microenvironment changes during chemotherapy for patients with choriocarcinoma or testicular tumor-curable with chemotherapy only, will rescue tumor cells from cell cycle arrest rendering them sensitive to chemotherapy. This new combinative therapy of concurrently using endocrine hormones and chemotherapy is defined as choriocarcinoma-mimic chemotherapy or neo-endocrinochemotherapy to distinguish the routine term of endocrinochemotherapy and is expected to be a novel approach to enhance chemotherapeutic efficacy in clinic.