Cellular metabolic reprogramming is now recognized as a hallmark of tumors. Altered tumor metabolism determines the malignant biological behaviors and phenotypes of cancer. More recently, studies have begun to reveal that cancer cells generally exhibit increased glycolysis or oxidative phosphorylation (OXPHOS) for Adenosine Triphosphate(ATP)generation, which is frequently associated with drug resistance. The metabolism of drug-resistant cells is regulated by the PI3K/AKT/mTOR pathway which ultimately confer cancer cells drug resistance phenotype. The key enzymes involved in glycolysis and the key molecules in relevant pathways have been used as targets to reverse drug resistance. In this review, we highlight our current understanding of the role of metabolic symbiosis in therapeutic resistance and discuss the ongoing effort to develop metabolic inhibitors as anti-cancer drugs to overcome drug resistance to classical chemotherapy.

Gonadotropin-releasing hormone analogs (GnRHa) substantially contribute to the adjuvant treatment of premenopausal patients with breast cancer. Several studies have shown that GnRHa can inhibit the progression of breast cancer and improve the survival of premenopausal patients with breast cancer.¹ In addition, studies have shown that treatment with GnRHa appeared to protect against ovarian failure, reducing premature ovarian insufficiency (POI) incidence and the risk of early menopause and improving the rate of menses recovery and pregnancy after chemotherapy.^2-6 Therefore, European Society of Medical Oncology guidelines and European Society of Human Reproduction and Embryology guidelines have recommended GnRHa to protect ovarian function.^7,8 However, there are still conflicting evidences about the effect of GnRHa in protecting ovarian function during tumor chemoradiotherapy; the evaluation criteria of ovarian function are also inconsistent, and the mechanism is not clear.⁹

Possible role of Pax-6 in promoting breast cancer cell proliferation and tumorigenesis Breast cancer;Lentivirus;Pax6 shRNA; Pax 6, a member of the paired box (Pax) family, has been implicated in oncogenesis. However, its therapeutic potential has been never examined in breast cancer. To explore the role of Pax6 in breast cancer development, a lentivirus based short hairpin RNA (shRNA) delivery system was used to knockdown Pax6 expression in estrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cells. Effect of Pax6 silencing on breast cancer cell proliferation and tumorigenesis was analyzed. Pax6-RNAi-lentivirus infection remarkably downregulated the expression levels of Pax6 mRNA and protein in MCF-7 and MDA-MB-231 cells. Accordingly, the cell viability, DNA synthesis, and colony formation were strongly suppressed, and the tumorigenesis in xenograft nude mice was significantly inhibited. Moreover, tumor cells were arrested at G0/G1 phase after Pax6 was knocked down. Pax6 facilitates important regulatory roles in breast cancer cell proliferation and tumor progression, and could serve as a diagnostic marker for clinical investigation.