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The Ubiquitin-Proteasome Pathway and Resistance Mechanisms Developed Against the Proteasomal Inhibitors in Cancer Cells       
Yazarlar (2)
Azmi Yerlikaya
Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Dr. Öğr. Üyesi Ertan KANBUR Dr. Öğr. Üyesi Ertan KANBUR
Kırşehir Ahi Evran Üniversitesi, Türkiye
Devamını Göster
Özet
Background: The ubiquitin-proteasome pathway is crucial for all cellular processes and is, therefore, a critical target for the investigation and development of novel strategies for cancer treatment. In addition, approximately 30% of newly synthesized proteins never attain their final conformations due to translational errors or defects in post-translational modifications; therefore, they are also rapidly eliminated by the ubiquitin-proteasome pathway.
Objective: Here, an effort was made to outline the recent findings deciphering the new molecular mechanisms involved in the regulation of ubiquitin-proteasome pathway as well as the resistance mechanisms developed against proteasome inhibitors in cell culture experiments and in the clinical trials.
Results: Since cancer cells have higher proliferation rates and are more prone to translational errors, they require the ubiquitin-proteasome pathway for selective advantage and sustained proliferation. Therefore, drugs targeting the ubiquitin-proteasome pathway are promising agents for the treatment of both hematological and solid cancers.
Conclusion: A number of proteasome inhibitors are approved and used for the treatment of advanced and relapsed multiple myeloma. Unfortunately, drug resistance mechanisms may develop very fast within days of the start of the proteasome inhibitor-treatment either due to the inherent or acquired resistance mechanisms under selective drug pressure. However, a comprehensive understanding of the mechanisms leading to the proteasome inhibitor-resistance will eventually help the design and development of novel strategies involving new drugs and/or drug combinations for the treatment of a number of cancers.
Anahtar Kelimeler
Bortezomib | cancer | myeloma | proteasome | resistance | ubiquitin
Makale Türü Diğer (Teknik, not, yorum, vaka takdimi, editöre mektup, özet, kitap krıtiği, araştırma notu, bilirkişi raporu ve benzeri)
Makale Alt Türü SCI, SSCI, AHCI, SCI-Exp dergilerinde yayımlanan teknik not, editöre mektup, tartışma, vaka takdimi ve özet türünden makale
Dergi Adı CURRENT DRUG TARGETS
Dergi ISSN 1389-4501 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili Türkçe
Basım Tarihi 01-2020
Cilt No 21
Sayı 13
Sayfalar 1313 / 1325
Doi Numarası 10.2174/1389450121666200525004714
Makale Linki http://dx.doi.org/10.2174/1389450121666200525004714