Discussion
NSCLC, SCLC, MDA-MB-436, xenograft-tumors
SCLC, BREAST CANCER, PROLIFERATION, COLON CANCER, PANCREATIC CANCER, NSCLC
This study will provide evidence on efficacy and safety fluzoparib combined with anlotinib in ES-SCLC, which may be used as a candidate standard therapy.A previous study demonstrated anlotinib has a high efficacy and safety profile in patients with advanced NSCLC [A multicenter, randomized, double-blind study ALTER1202 enrolled 11 study centers nationwide was designed to observe 120 patients with pathologically confirmed SCLC who had been treated with at least two prior systemic chemotherapy regimens. The main efficacy indicator is PFS [Fluzoparib is an inhibitor of poly ADP ribose polymerase (PARP, including PARPl, PARP2 and PARP3). Previous studies showed that fluzoparib has a strong inhibitory effect on PARP1 activity at the molecular and cellular levels [In vitro studies showed that fluzoparib significantly inhibited the proliferation of V-C8 cell and MBA-MB-436 cell with an IC50 of approximately 100 nM and 1 μM, respectively. Fluzoparib and olaparib presented almost the same activity in V-C8 and MBA-MB-436 cells. In addition, fluzoparib could also intensify the inhibitory effect on cell proliferation via synergizing with TMZ, MMC or CDDP, and fluzoparib and TMZ showed the greatest synergy, which is about fourfold over EMZ alone [The effect of fluozoparib on xenograft-tumors in nude mice with injected MX-1 cell (breast cancer BRCA1/2 mutation cell), MDA-MB-436 cell (breast cancer BRCA2 mutation cell)), capan-1 cell (pancreatic cancer cell with BRCA1 mutation) and SW-620 cell (colon cancer cell with reduced BRCA expression) was conducted [In clinical practice, parts of patients who are terrified of the chemotherapy due to the tolerability concerns, will be enrolled in the present study. What should be noted is that previously untreated ES-SCLC with failure of first-line platinum-based chemotherapy will receive fluzoparib plus anlotinib. Thus, this study will provide preliminary evidence of this combination therapy in the first-line setting. We wish that the present study will find a potent chemo-free treatment approach and bring new light of hope for ES-SCLC patients after failure of first-line platinum-based chemotherapy.