Pan Cyclin-Dependent Kinase Inhibitors for the Treatment of Breast Cancer

Abstract

Background: Despite extensive attempts for the treatment of breast cancer (BC), it is the most prevalent cancer type among women, and its treatment remains elusive, particularly in patients with advanced disease. Although there are several therapeutic options, none of them is effective for complete relief, especially in metastatic patients. Cancer cells exhibit a high proliferation rate, which is usually associated with the dysregulation of cell cycle progress. Various proteins such as cyclin-dependent kinases (CDKs) and cyclins are involved in cell cycle modulation. Methods: Databases including PubMed, Scopus, WebofScience and Google Scholar were used to extract information. Articles published in English until 2022 were used. Results: Regarding the dysregulation of various CDKs in several cancer types, the pharmacologicalinhibitors of CDKs have extensively been evaluated to treat several cancer types such as BC. The blockade of CDKs strongly suppresses tumor growth through cell cycle arrest. Moreover, the combination of CDK inhibitors and other anti-cancer therapeutics has demonstrated potent synergistic effects on the treatment of various cancers. Conclusion: Therefore, various CDK inhibitors have been designed and evaluated as antiproliferative therapeutics to suppress the proliferation of cancer cells. Pan CDK inhibitors, including flavopiridol, dinaciclib, purvalanol A, SNS-032, and roscovitine, are the most effective CDK inhibitors investigated in several studies. They inhibit various CDKs such as the CDK1, 2, 4, 5, 6, 7, and 9. In this review, it is attempted to discuss the efficacy of Pan CDK inhibitors as an anti-cancer therapy in BC.

Graph theoretical analysis, pharmacoinformatics and molecular docking investigation of Chalcone-Schiff base hybrids as Cyclin-Dependent kinase inhibitors

“…They are divided into members that control proliferation, such as CDK1, 2, 3, 4 and 6, members that are involved in transcription, such as CDK7, 8, 9, 11, 12 and 13. Given their significant influence over the regulation of the growth of cancer cells, it is proposed that blocking these molecules may represent a highly effective anti-cancer treatment strategy (Izadi et al, 2023). Thus, an attempt was made to predict the biological potential of the previously described Chalcone-Schiff base hybrids based on the network pharmacology and other in silico studies.…”

“…Due to the significance of these factors in the regulation of cancer cell proliferation, it is suggested that the blockade of these molecules can be considered a potent anti-cancer therapeutic approach in breast cancer. The substantial enhancement of cancer cell proliferation by increased CDK activity suggests that CDK inhibitors could be a unique and viable therapeutic method for treating cancer (Izadi et al, 2023). The primary activators of the cell cycle are CDKs (cyclin-dependent kinases), which phosphorylate essential substrates to accelerate DNA synthesis and mitosis.…”

“…Chemotherapies often target rapidly dividing cells, which can include both cancer and normal cells, leading to side effects. CDK inhibitors, by selectively targeting the abnormal cell cycle regulation in cancer cells, might offer a more targeted and less toxic therapeutic approach (Izadi et al, 2023). Based on the above results, the CDK inhibitory potential of the designed compounds was further analysed through molecular docking studies.…”