Triple-negatif meme kanseri hücrelerinde CDK4/6 İnhibitörlerinin (Ribociclib ve Palbociclib) Enzalutamid ile Kombine Edilmesinin Karşılaştırmalı Analizi

Abstract

Triple-negatif meme kanseri (TNMK), kötü prognozu nedeniyle zorlu bir alt tür olarak kabul edilmektedir. Son moleküler profil çalışmaları, androjen reseptörünü (AR) ifade eden önemli bir alt küme ortaya çıkarmıştır ki bu alt küme, AR engelleyici ajanlara cevap verebilir ve potansiyel bir etkili tedavi stratejisi sunabilir. Bu çalışma, AR antagonist enzalutamid (ENZA) ile CDK4/6 inhibitörleri palbosislib (PB) veya ribosiklib (RB) kombinasyonunun potansiyel sinerjistik sitotoksik ve apoptotik etkilerini araştırmayı ve bu kombinasyonların TNMK hücrelerindeki etkinliğini karşılaştırmayı amaçlamaktadır. Sonuçlar, ENZA'nın PB veya RB ile kombinasyonunun, test edilen tüm TNMK hücre hatlarında sinerjistik sitotoksik etkileri tetiklediğini ortaya koydu. ENZA'nın PB ile sinerjistik sitotoksik kombinasyonları hiçbir TNMK hücre hattında apoptozu indirgemedi, ancak ENZA+RB kombinasyonları sinerjistik apoptotik etki gösterdi. Bu çalışma, ENZA+RB kombinasyonunun apoptozu artırıcı etkisi nedeniyle daha olumlu olabileceğini önermektedir. Ancak, bu verilerin detaylı in vivo ve klinik çalışmalarla daha fazla desteklenmesi gerekmektedir.

Keywords

• Triple-negative breast cancer
• enzalutamide
• palbociclib
• ribociclib

Comparative Analysis of CDK4/6 Inhibitors (Ribociclib and Palbociclib) combined with Enzalutamide in Triple-negative breast cancer cells

Abstract

Triple-negative breast cancer (TNBC) is recognized as a challenging subtype due to its poor prognosis. Recent molecular profiling studies have unveiled a significant subset expressing the androgen receptor (AR) subset which may respond to AR-blocking agents, offering a potentially effective treatment strategy. This study aims to investigate the potential synergistic cytotoxic and apoptotic effects of the AR antagonist enzalutamide (ENZA) in combination with CDK4/6 inhibitors palbociclib (PB) or ribociclib (RB) and compare the effectiveness of these combinations in TNBC cells. Results revaled that ENZA in combination with PB or RB induced synergistic cytotoxic cytotoxicity in all tested TNBC cell lines. While synergistic cytotoxic combinations of ENZA with PB did not induce apoptosis in any TNBC cell line, ENZA+RB combinations exhibited a synergistic apoptotic effect. This study suggests that the ENZA+RB combination may be more favorable due to its apoptosis-inducing effect. However, these data need to be further supported by detailed in vivo and clinical studies

Keywords

• Triple-negative breast cancer
• enzalutamide
• palbociclib
• ribociclib

Supporting Institution

This study received project support from the Turkish Medical Oncology Society (Proje No: P-TTOD-2021-142).

Ethical Statement

Ethical clearance is not required as the study was conducted using commercial cell lines

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