(精选)【医学英文课件】 Nuovi pathways nuovi farmaci quali prospettive教学课件.pptVIP

Angelo Di Leo “Sandro Pitigliani” Medical Oncology Department Hospital of Prato Istituto Toscano Tumori, Prato, Italy Nuovi pathways nuovi farmaci: quali prospettive? Applicability Company (1) Advisory role Yes AstraZeneca, Bayer, Celgene, Lilly, Novartis, Pfizer, Roche 　 (2) Stock ownership/profit　 None 　 (3) Patent royalties/licensing fees　 None 　 (4) Lecture fees Yes AstraZeneca, Eisai, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche (5) Manuscript fees None 　 (6) Scholarship fund None 　 (7) Other remuneration None 　 Conflict of Interest Disclosure Focus on ER+ / HER-2 negative breast cancer CDK 4-6 inhibitors PI3K inhibitors Cooperation between ER and Cyclic D1 pathways enhances proliferation in luminal breast cancer Cyclin D1 CDK4-6 ER p Rb Inhibitory control Inhibitory control Cell Cycle: G1 S proliferation Inhibitors: Palbociclib Abemaciclib Ribociclib PD 0332991 has shown activity preferentially on ER+, luminal breast cancer cell lines with or without HER2 amplification. RB1, cyclin D1, and CDKN2A (p16) were differentially expressed - with higher levels of RB1 and cyclin D1, and lower levels of p16, in the sensitive group. Resistance to PD in many of the nonluminal breast cancer cell lines may be explained by the absence of pRb. Recent publications highlighted the lack of pRb in basal-like breast cancer tissue and observed that pRb depletion can result in the characteristic epithelial-to-mesenchymal transition changes The lack of activity of a CDK4/6 inhibitor in cell lines and tumors that lack pRb can be explained by the fact that cyclin D1 does not offer G1 control in the absence of pRb. Finn et al, BCR 2011 IC50 nM Subtype Luminal Non - luminal/post EMT HER2 Amplified Non - luminal Immortalized Subtype Luminal Non - luminal/post EMT HER2 Amplified Non - luminal Immortalized Considerations on CDK4/6 inhibitor activity We have results from two Phase III trials testing CDK 4-6 inhibitors in the first-line tre