Venetoclax in combination with nucleoside analogs in acute myelogenous leukemia

Abstract

Purpose of reviewVenetoclax in combination with nucleoside analogs such as hypomethylating agents (HMA) and low-dose cytarabine (LDAC) has led to unprecedented response and survival outcomes in patients with acute myeloid leukemia (AML). This has spurred the development of regimens combining venetoclax with other nucleoside analogs with distinct mechanisms of action. Here, we review older and newer nucleoside analogs, the rationale for their combination with venetoclax, and clinical evidence for the combination when available. Recent findingsVenetoclax with HMA prolonged survival in a phase 3 study. Additionally, biologic correlates of response and resistance to venetoclax with HMA have been identified. The addition of venetoclax to standard intensive regimens containing higher doses of cytarabine and purine nucleoside analogs are safe and induce very high rates of remission and measurable residual disease negativity (MRD) negativity in newly diagnosed and relapsed/refractory AML. Investigational nucleoside analogs aim to improve upon the safety, bioavailability, or efficacy of approved venetoclax combinations and are currently being evaluated in clinical studies.

DNA methylation meningioma biomarkers: attributes and limitations

“…As adenosine analogs DNMTi, cladribine and fludarabine can inhibit DNA methylation from three major aspects. They can incorporate into DNA sequences to form triphosphate deoxynucleotide to inhibit DNA synthesis ( Greene et al, 2020 ; Ball et al, 2022 ). They can control proliferating cell nuclear antigen (PCNA) to induce DNMT1 activity on semi-methylated DNA by increasing p21 level ( Zhang et al, 2022 ).…”

“…Cladribine has good oral bioavailability, and has the potential to penetrate the blood–brain barrier ( Ford et al, 2022 ). Fludarabine is a fluorinated derivative of adenosine, which can prevent the deamination of adenosine deaminase ( Greene et al, 2020 ; Ball et al, 2022 ). Guadecitabine is a drug that belongs to the class of hypomethylating agents and is used for the treatment of various types of cancer, including myelodysplastic syndromes and acute myeloid leukemia.…”

A-Review on Anticancer Agents: Conventional Drugs and Novel Target Specific Inhibitors

“…7) and thioguanine belongs to this category Mercaptopurine is converted to thioinosinic acid in presence of enzyme hypoxanthine guanine phosho ribosyl transferase (HGPRT). Thioinosinic acid inhibits some enzymes which are responsible for the synthesis of purine 26 .…”