TY - JOUR
T1 - Mechanisms of resistance to hypomethylating agents and BCL-2 inhibitors
AU - Desai, Sudhamsh Reddy
AU - Chakraborty, Samarpana
AU - Shastri, Aditi
N1 - Publisher Copyright:
© 2023
PY - 2023/12
Y1 - 2023/12
N2 - Myeloid malignancies such as myelodysplastic syndrome (MDS) & acute myeloid leukemia (AML) are clonal diseases that emerge and progress due to the expansion of disease-initiating aberrant hematopoietic stem cells, that are not eliminated by conventional cytotoxic therapies. Hypomethylating agents(HMA), azacytidine and decitabine are the first line agents for treatment of MDS and a combination with BCL-2 inhibitor, venetoclax, is approved for AML induction in patients above 75 years and is also actively being investigated for use in high risk MDS. Resistance to these drugs has become a significant clinical challenge in treatment of myeloid malignancies. In this review, we discuss molecular mechanisms underlying the development of resistance to HMA and venetoclax. Insights into these mechanisms can help identify potential biomarkers for resistance prediction, aid in the development of combination therapies and strategies to prevent resistance and advance the field of cancer therapeutics.
AB - Myeloid malignancies such as myelodysplastic syndrome (MDS) & acute myeloid leukemia (AML) are clonal diseases that emerge and progress due to the expansion of disease-initiating aberrant hematopoietic stem cells, that are not eliminated by conventional cytotoxic therapies. Hypomethylating agents(HMA), azacytidine and decitabine are the first line agents for treatment of MDS and a combination with BCL-2 inhibitor, venetoclax, is approved for AML induction in patients above 75 years and is also actively being investigated for use in high risk MDS. Resistance to these drugs has become a significant clinical challenge in treatment of myeloid malignancies. In this review, we discuss molecular mechanisms underlying the development of resistance to HMA and venetoclax. Insights into these mechanisms can help identify potential biomarkers for resistance prediction, aid in the development of combination therapies and strategies to prevent resistance and advance the field of cancer therapeutics.
KW - AML
KW - Azacytidine
KW - Decitabine
KW - Therapy resistance
KW - Venetoclax
UR - http://www.scopus.com/inward/record.url?scp=85176144902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85176144902&partnerID=8YFLogxK
U2 - 10.1016/j.beha.2023.101521
DO - 10.1016/j.beha.2023.101521
M3 - Review article
C2 - 38092478
AN - SCOPUS:85176144902
SN - 1521-6926
VL - 36
JO - Best Practice and Research: Clinical Haematology
JF - Best Practice and Research: Clinical Haematology
IS - 4
M1 - 101521
ER -
