Comparative Analysis of CDK4/6 Inhibitors (Ribociclib and Palbociclib) combined with Enzalutamide in Triple-negative breast cancer cells
Öz
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
Anahtar Kelimeler
Triple-negative breast cancer enzalutamide palbociclib ribociclib
Etik Beyan
Ethical clearance is not required as the study was conducted using commercial cell lines
Destekleyen Kurum
This study received project support from the Turkish Medical Oncology Society (Proje No: P-TTOD-2021-142).
Kaynakça
- Sung H., et al., “Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” CA. Cancer J. Clin., vol. 71, no. 3, pp. 209–249, May 2021, doi: 10.3322/caac.21660.
- Cleator, S., W. Heller, and R. C. Coombes, “Triple-negative breast cancer: therapeutic options,” Lancet Oncology, vol. 8, no. 3. Elsevier, pp. 235–244, Mar. 2007. doi: 10.1016/S1470-2045(07)70074-8.
- Kumar P. and R. Aggarwal, “An overview of triple-negative breast cancer,” Archives of Gynecology and Obstetrics, vol. 293, no. 2. 2016. doi: 10.1007/s00404-015-3859-y.
- Coussy F., et al., “Response to mTOR and PI3K inhibitors in enzalutamide-resistant luminal androgen receptor triple-negative breast cancer patient-derived xenografts,” Theranostics, vol. 10, no. 4, 2020, doi: 10.7150/thno.36182.
- Rampurwala, M., K. B. Wisinski, and R. O’Regan, “Role of the androgen receptor in triple-negative breast cancer,” Clin. Adv. Hematol. Oncol., vol. 14, no. 3, 2016.
- Traina T. A., et al., “Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer,” J. Clin. Oncol., vol. 36, no. 9, 2018, doi: 10.1200/JCO.2016.71.3495.
- Spring, L. M., “CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions,” Current Oncology Reports, vol. 21, no. 3. 2019. doi: 10.1007/s11912-019-0769-3.
- Turner N. C., et al., “Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer,” N. Engl. J. Med., vol. 373, no. 3, 2015, doi: 10.1056/nejmoa1505270.
- Jacob, A., et al., “Androgen receptor signaling in prostate cancer and therapeutic strategies,” Cancers, vol. 13, no. 21. 2021. doi: 10.3390/cancers13215417.
- G. Murphy, C. G., “The Role of CDK4/6 Inhibitors in Breast Cancer,” Current Treatment Options in Oncology, vol. 20, no. 6. 2019. doi: 10.1007/s11864-019-0651-4.
- Choupani, E., et al., “Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells,” PLoS One, vol. 17, no. 12 December, 2022, doi: 10.1371/journal.pone.0279522.
- Liu C. Y., et al., “Combination of palbociclib with enzalutamide shows in vitro activity in RB proficient and androgen receptor positive triple negative breast cancer cells,” PLoS One, vol. 12, no. 12, 2017, doi: 10.1371/journal.pone.0189007.
- Chou, T. C., “Frequently asked questions in drug combinations and the mass-action law-based answers,” Synergy, vol. 1, no. 1. 2014. doi: 10.1016/j.synres.2014.07.003.
- Caiazza F., et al., “Preclinical evaluation of the AR inhibitor enzalutamide in triple-negative breast cancer cells,” Endocr. Relat. Cancer, vol. 23, no. 4, 2016, doi: 10.1530/ERC-16-0068.
- Li T., et al., “Ribociclib (LEE011) suppresses cell proliferation and induces apoptosis of MDA-MB-231 by inhibiting CDK4/6-cyclin D-Rb-E2F pathway,” Artif. Cells, Nanomedicine Biotechnol., vol. 47, no. 1, 2019, doi: 10.1080/21691401.2019.1670670.
- Abazid, A., et al., “The androgen receptor antagonist enzalutamide induces apoptosis, dysregulates the heat shock protein system, and diminishes the androgen receptor and estrogen receptor β1 expression in prostate cancer cells,” J. Cell. Biochem., vol. 120, no. 10, 2019, doi: 10.1002/jcb.28929.
- Chang, C. Y., J. T. Chen, T. H. Chen, and R. M. Chen, “Enzalutamide Induces Apoptotic Insults to Human Drug-Resistant and -Sensitive Glioblastoma Cells via an Intrinsic Bax-Mitochondrion-Cytochrome C Caspase Cascade Activation Pathway,” Molecules, vol. 27, no. 19, 2022, doi: 10.3390/molecules27196666.
Triple-negatif meme kanseri hücrelerinde CDK4/6 İnhibitörlerinin (Ribociclib ve Palbociclib) Enzalutamid ile Kombine Edilmesinin Karşılaştırmalı Analizi
Öz
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.
Anahtar Kelimeler
Triple-negative breast cancer enzalutamide palbociclib ribociclib
Kaynakça
- Sung H., et al., “Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” CA. Cancer J. Clin., vol. 71, no. 3, pp. 209–249, May 2021, doi: 10.3322/caac.21660.
- Cleator, S., W. Heller, and R. C. Coombes, “Triple-negative breast cancer: therapeutic options,” Lancet Oncology, vol. 8, no. 3. Elsevier, pp. 235–244, Mar. 2007. doi: 10.1016/S1470-2045(07)70074-8.
- Kumar P. and R. Aggarwal, “An overview of triple-negative breast cancer,” Archives of Gynecology and Obstetrics, vol. 293, no. 2. 2016. doi: 10.1007/s00404-015-3859-y.
- Coussy F., et al., “Response to mTOR and PI3K inhibitors in enzalutamide-resistant luminal androgen receptor triple-negative breast cancer patient-derived xenografts,” Theranostics, vol. 10, no. 4, 2020, doi: 10.7150/thno.36182.
- Rampurwala, M., K. B. Wisinski, and R. O’Regan, “Role of the androgen receptor in triple-negative breast cancer,” Clin. Adv. Hematol. Oncol., vol. 14, no. 3, 2016.
- Traina T. A., et al., “Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer,” J. Clin. Oncol., vol. 36, no. 9, 2018, doi: 10.1200/JCO.2016.71.3495.
- Spring, L. M., “CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions,” Current Oncology Reports, vol. 21, no. 3. 2019. doi: 10.1007/s11912-019-0769-3.
- Turner N. C., et al., “Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer,” N. Engl. J. Med., vol. 373, no. 3, 2015, doi: 10.1056/nejmoa1505270.
- Jacob, A., et al., “Androgen receptor signaling in prostate cancer and therapeutic strategies,” Cancers, vol. 13, no. 21. 2021. doi: 10.3390/cancers13215417.
- G. Murphy, C. G., “The Role of CDK4/6 Inhibitors in Breast Cancer,” Current Treatment Options in Oncology, vol. 20, no. 6. 2019. doi: 10.1007/s11864-019-0651-4.
- Choupani, E., et al., “Combination of androgen receptor inhibitor enzalutamide with the CDK4/6 inhibitor ribociclib in triple negative breast cancer cells,” PLoS One, vol. 17, no. 12 December, 2022, doi: 10.1371/journal.pone.0279522.
- Liu C. Y., et al., “Combination of palbociclib with enzalutamide shows in vitro activity in RB proficient and androgen receptor positive triple negative breast cancer cells,” PLoS One, vol. 12, no. 12, 2017, doi: 10.1371/journal.pone.0189007.
- Chou, T. C., “Frequently asked questions in drug combinations and the mass-action law-based answers,” Synergy, vol. 1, no. 1. 2014. doi: 10.1016/j.synres.2014.07.003.
- Caiazza F., et al., “Preclinical evaluation of the AR inhibitor enzalutamide in triple-negative breast cancer cells,” Endocr. Relat. Cancer, vol. 23, no. 4, 2016, doi: 10.1530/ERC-16-0068.
- Li T., et al., “Ribociclib (LEE011) suppresses cell proliferation and induces apoptosis of MDA-MB-231 by inhibiting CDK4/6-cyclin D-Rb-E2F pathway,” Artif. Cells, Nanomedicine Biotechnol., vol. 47, no. 1, 2019, doi: 10.1080/21691401.2019.1670670.
- Abazid, A., et al., “The androgen receptor antagonist enzalutamide induces apoptosis, dysregulates the heat shock protein system, and diminishes the androgen receptor and estrogen receptor β1 expression in prostate cancer cells,” J. Cell. Biochem., vol. 120, no. 10, 2019, doi: 10.1002/jcb.28929.
- Chang, C. Y., J. T. Chen, T. H. Chen, and R. M. Chen, “Enzalutamide Induces Apoptotic Insults to Human Drug-Resistant and -Sensitive Glioblastoma Cells via an Intrinsic Bax-Mitochondrion-Cytochrome C Caspase Cascade Activation Pathway,” Molecules, vol. 27, no. 19, 2022, doi: 10.3390/molecules27196666.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Biyokimya ve Hücre Biyolojisi (Diğer) |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Erken Görünüm Tarihi | 21 Nisan 2024 |
| Yayımlanma Tarihi | 15 Nisan 2024 |
| Gönderilme Tarihi | 28 Ocak 2024 |
| Kabul Tarihi | 26 Şubat 2024 |
| Yayımlandığı Sayı | Yıl 2024 Cilt: 7 Sayı: 1 |
