The MCL-1 targeting effect of alvocidib potentiates the activity of cytarabine and mitoxantrone in a time-sequential regimen in AML

Kim, Wontak; Bahr, Brigham L.; Soh, Katherine K.; Bearss, Jeremiah J.; Lee, Ye Sol; Peterson, Peter; Whatcott, Clifford J.; Siddiqui‐Jain, Adam; Weitman, Steven; Bearss, David J.; Warner, Steven L.

doi:10.1016/j.clml.2015.07.041

Cited by 1 publication

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“…In addition to acting as a pan-CDK inhibitor, flavopiridol has also been shown to induce apoptosis through the downregulation of anti-apoptotic proteins such as Bcl-2 and Mcl-1 (117,118). As previously discussed, overexpression of Mcl-1 in AML is often synonymous with disease relapses and the ability of flavopiridol to repress the expression of Mcl-1 is believed to contribute to the synergism found in the FLAM regimen by potentiating the activities of cytarabine and mitoxantrone (119). Despite the remarkable improvement in complete remission rates following FLAM treatment, there were no difference in overall survival or event-free survival when compared to the conventional “7 + 3” regimen (103).…”

Section: Flam – Opening New Doors In Amlmentioning

confidence: 99%

Recent Treatment Advances and the Role of Nanotechnology, Combination Products, and Immunotherapy in Changing the Therapeutic Landscape of Acute Myeloid Leukemia

Chen

Gilabert-Oriol²,

Bally

et al. 2019

Pharm Res

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Acute myeloid leukemia (AML) is the most common acute leukemia that is becoming more prevalent particularly in the older (65 years of age or older) population. For decades, “7 + 3” remission induction therapy with cytarabine and an anthracycline, followed by consolidation therapy, has been the standard of care treatment for AML. This stagnancy in AML treatment has resulted in less than ideal treatment outcomes for AML patients, especially for elderly patients and those with unfavourable profiles. Over the past two years, six new therapeutic agents have received regulatory approval, suggesting that a number of obstacles to treating AML have been addressed and the treatment landscape for AML is finally changing. This review outlines the challenges and obstacles in treating AML and highlights the advances in AML treatment made in recent years, including Vyxeos®, midostaurin, gemtuzumab ozogamicin, and venetoclax, with particular emphasis on combination treatment strategies. We also discuss the potential utility of new combination products such as one that we call “EnFlaM”, which comprises an encapsulated nanoformulation of flavopiridol and mitoxantrone. Finally, we provide a review on the immunotherapeutic landscape of AML, discussing yet another angle through which novel treatments can be designed to further improve treatment outcomes for AML patients.

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Section: Flam – Opening New Doors In Amlmentioning

confidence: 99%