TY - JOUR
T1 - Targeting MCL-1 in hematologic malignancies
T2 - Rationale and progress
AU - Wei, Andrew H.
AU - Roberts, Andrew W.
AU - Spencer, Andrew
AU - Rosenberg, Aaron Seth
AU - Siegel, David
AU - Walter, Roland B.
AU - Caenepeel, Sean
AU - Hughes, Paul
AU - McIver, Zach
AU - Mezzi, Khalid
AU - Morrow, Phuong Khanh
AU - Stein, Anthony
PY - 2020/1/1
Y1 - 2020/1/1
N2 - Myeloid cell leukemia sequence 1 (MCL-1) is an antiapoptotic protein that plays a key role in promoting cell survival in multiple myeloma (MM), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL). Overexpression of MCL-1 is associated with treatment resistance and poor prognosis; thus, MCL-1 inhibitors are rational therapeutic options for malignancies depending on MCL-1. Several MCL-1 inhibitors have entered clinical trials, including AZD5991, S64315, AMG 176, and AMG 397. A key area of investigation is whether MCL-1 inhibitors will complement the activity of BCL-2 inhibitors, such as venetoclax, and synergistically enhance anti-tumor efficacy when given in combination with other anti-cancer drugs. Another important question is whether a safe therapeutic window can be found for this new class of inhibitors. In summary, inhibition of MCL-1 shows potential as a treatment for hematologic malignancies and clinical evaluation of MCL-1 inhibitors is currently underway.
AB - Myeloid cell leukemia sequence 1 (MCL-1) is an antiapoptotic protein that plays a key role in promoting cell survival in multiple myeloma (MM), acute myeloid leukemia (AML), and non-Hodgkin lymphoma (NHL). Overexpression of MCL-1 is associated with treatment resistance and poor prognosis; thus, MCL-1 inhibitors are rational therapeutic options for malignancies depending on MCL-1. Several MCL-1 inhibitors have entered clinical trials, including AZD5991, S64315, AMG 176, and AMG 397. A key area of investigation is whether MCL-1 inhibitors will complement the activity of BCL-2 inhibitors, such as venetoclax, and synergistically enhance anti-tumor efficacy when given in combination with other anti-cancer drugs. Another important question is whether a safe therapeutic window can be found for this new class of inhibitors. In summary, inhibition of MCL-1 shows potential as a treatment for hematologic malignancies and clinical evaluation of MCL-1 inhibitors is currently underway.
KW - Acute myeloid leukemia
KW - BH3-mimetic
KW - MCL-1 inhibitor
KW - Multiple myeloma
KW - Non-Hodgkin lymphoma
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U2 - 10.1016/j.blre.2020.100672
DO - 10.1016/j.blre.2020.100672
M3 - Review article
C2 - 32204955
AN - SCOPUS:85081954593
JO - Blood Reviews
JF - Blood Reviews
SN - 0268-960X
M1 - 100672
ER -