Lancet Oncology: New pathway stymied for DNA repair drugs combined with chemotherapy can suppress ovarian cancer

High-level slurryovarian cancer(HGSOC) is the most common type of ovarian epithelial cancer, the degree of malignancy is high, prone to metastasis, so most patients are in the advanced stage of treatmentOf course, there are also a small number of patients due to accidental factors were detected early, the cure rate is close to 100%In its first randomized clinical trial, a drug called ATR, a protein needed to keep cancer cells growing and dividing tenaciously, showed considerable advantage in combining chemotherapy with patients with common ovarian cancer, a new study showedthe study, led by Panagiotis A Konstantinopoulos, M.D., director of gynaecological oncology transformation research at Dana Fab in the United States, and published June 15 in theLancetOncologyTitled "Berzosertib plus gemcitabine versus gemcitabine alone in platinum-rhoedt high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial"In this multicenter, open-label, randomized Phase 2 study, researchers recruited women with recurrent, platinum-resistant high-level slurry-based ovarian cancer at 11 centers in the U.SExperimental Therapeutics Clinical Trial network, and recruited women who had received unlimited cytotoxicity treatments in platinum-sensitive environments, but did not receive more than one cell-resistant treatment in a platinum-resistant environmentBetween 14 February 2017 and 7 September 2018, they evaluated 88 patients recruited and selected 70 patients as subjects and randomly assigned them to treatment alone in Gisitabin (36 patients) and Gisitabin United Bezosettib (34 patients)patients were randomly assigned to two groups, received intravenous giselite (1000 mg/m 2) on the first and 8th days, or on the 2nd and 9th days of the 21-day cycle received The Intravenous Injection of Bezosettib (210 mg/m2) until the condition worsened or became intolerabletoxicUse Theradex interactive network response system to group randomly, layered at no platinum intervals, with a block size of 6After random grouping of centers, patients and researchers were informed of the treatment taskThe main focus of the study was to assess the survival rate of progressionless and to analyse all patients who received the drugstudy showed that the median follow-up time for the Gisitabin United Bezossetib group was 53.2 weeks, while the Gisitabin group alone had 43.0 weeksThe median progression survival period for the Gixithabin United Bezositin group is 22.9 weeks, and the Jicitha-Bin group alone is 14.7 weeksThe most common treatment-related level 3 or 4 adverse reactions were a decrease in the neutrophil count (14 of the 36 patients in the Gisitabingroup alone, compared with 16 of the 34 patients in the Gisitabin combined Bezositin group) and the platelet count decreased (2 cases , 6% compared to 8 casesThere were 10 (28%) serious adverse reactions in the Gisitabin group alone, and 9 (26%) of the Gisitabin United Bezosettib groupOne case died of sepsis in the Jixithabin treatment group alone, while one death from pneumonia was caused by the Chiselthabin United Bezossetib treatment groupresults showed that the median progression-free survival of patients treated with Gixitabin alone was estimated at 14.7 weeksThe number of patients receiving combination treatment with Gisitabin and Bezo setib was 22.9 weeksThe difference was even greater in patients with the highest platinum resistance levels (i.e., those who progressed within 3 months of chemotherapy for platinum drugs): Gisitabin was 9 weeks and Gisitabin united Bezo settib group was 27.7 weeksThe side effects of the two groups were similarHowever, patients receiving combination therapy were more likely to develop low platelet levels"The unbridled proliferation of cancer cells puts a lot of pressure on the DNA replication process," explainsKonstantopoulos"ATR can help them overcome this pressure: its role is to coordinate the cessation of cell cycles to check whether DNA is intact or if it needs to be repairedDrugs that inhibit ATR deprive tumor cells of this ability to repair and may be particularly effective in the treatment of certain cancersresearchers say this is the first randomized study of ATR inhibitors of any type of tumorThis study shows that it is beneficial to treat Bezoseltib in conjunction with Giselabin in the treatment of platinum-resistant high-level slurry-based ovarian cancer Based on the above, the treatment of this combination is worthy of further study