HORMON POZİTİF METASTATİK MEME KANSERİ HÜCRE HATTINDA ABEMASİKLİB METOTREKSAT KOMBİNASYON TEDAVİSİNİN ETKİNLİĞİNİN DEĞERLENDİRİLMESİ
Project no. 22009 · Status: Kapanmış (Yayın bekleniyor) · 2020
Summary
<p>Breast cancer ranks first in cancer-related deaths in women. Despite significant advances in primary and adjuvant treatments for early-stage breast cancer, many patients develop systemic relapse. Hormone receptor status and Her-2 status are the most important predictive factors for treatment response in MMC. Hormone positive (HR) metastatic breast cancer creates patients with estrogen (ER) and/or progesterone receptor (PR) positivity. This group of diseases is generally considered to have a slower progression and a better prognosis than triple negative and HER-2 positive disease. Although life expectancy is prolonged with the use of endocrine therapy and/or chemotherapy combinations in HR MMK, only 5-10% of patients live more than 5 years. Average life expectancy is 18-24 months. The standard approach in the world in this group of metastatic disease is the use of CDK4/6 inhibitor combinations with endocrine therapy. Combination of CDK4/6 inhibitors with cytotoxic chemotherapy has shown different results in preclinical studies. Although the combination studies of CDK 4/6 inhibitors and chemotherapy initially suggested that there was no efficacy, subsequent evaluations revealed that the timing of use of two different molecules should be determined very well. Abemaciclib oral is an ATP competitive inhibitor of selective CDK4/6 and has been shown to have a significant effect in breast cancer with endocrine therapy combinations. Methotrexate, on the other hand, is an S phase specific antimetabolite agent and inhibits cell proliferation by interacting with purine and pyrimidine metabolism. In this study, it is planned to investigate possible synergistic cytotoxic effects of Abemaciclib and methotrexate in hormone positive, HER-2 negative and retinoblastoma intact MCF-7 and T47D breast carcinoma cell lines. With this combination, it is aimed to eliminate cells that survive senescence and return to the cycle and to provide a longer response to CDK 4-6 inhibitors.</p>