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Targeting oncogenic Notch signaling with SERCA inhibitors.
- Source :
-
Journal of hematology & oncology [J Hematol Oncol] 2021 Jan 06; Vol. 14 (1), pp. 8. Date of Electronic Publication: 2021 Jan 06. - Publication Year :
- 2021
-
Abstract
- P-type ATPase inhibitors are among the most successful and widely prescribed therapeutics in modern pharmacology. Clinical transition has been safely achieved for H <superscript>+</superscript> /K <superscript>+</superscript> ATPase inhibitors such as omeprazole and Na <superscript>+</superscript> /K <superscript>+</superscript> -ATPase inhibitors like digoxin. However, this is more challenging for Ca <superscript>2+</superscript> -ATPase modulators due to the physiological role of Ca <superscript>2+</superscript> in cardiac dynamics. Over the past two decades, sarco-endoplasmic reticulum Ca <superscript>2+</superscript> -ATPase (SERCA) modulators have been studied as potential chemotherapy agents because of their Ca <superscript>2+</superscript> -mediated pan-cancer lethal effects. Instead, recent evidence suggests that SERCA inhibition suppresses oncogenic Notch1 signaling emerging as an alternative to γ-secretase modulators that showed limited clinical activity due to severe side effects. In this review, we focus on how SERCA inhibitors alter Notch1 signaling and show that Notch on-target-mediated antileukemia properties of these molecules can be achieved without causing overt Ca <superscript>2+</superscript> cellular overload.
- Subjects :
- Animals
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacology
Enzyme Inhibitors chemistry
Enzyme Inhibitors pharmacology
Humans
Molecular Targeted Therapy
Neoplasms metabolism
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma drug therapy
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma metabolism
Receptors, Notch metabolism
Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism
Thapsigargin analogs & derivatives
Thapsigargin pharmacology
Thapsigargin therapeutic use
Antineoplastic Agents therapeutic use
Enzyme Inhibitors therapeutic use
Neoplasms drug therapy
Receptors, Notch antagonists & inhibitors
Sarcoplasmic Reticulum Calcium-Transporting ATPases antagonists & inhibitors
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1756-8722
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of hematology & oncology
- Publication Type :
- Academic Journal
- Accession number :
- 33407740
- Full Text :
- https://doi.org/10.1186/s13045-020-01015-9