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ABSTRACT
Introduction
The Ca2+ signaling toolkit is currently under investigation as a potential target for addressing the threat of cancer. A growing body of evidence suggests that calcium signaling plays a crucial role in promoting various aspects of cancer, including cell proliferation, progression, drug resistance, and migration-related activities. Consequently, focusing on these altered Ca2+ transporting proteins has emerged as a promising area of research for cancer treatment.
Areas Covered
This review highlights the existing research on the role of Ca2+-transporting proteins in cancer progression. It discusses the current studies evaluating Ca2+ channel/transporter/pump blockers, inhibitors, or regulators as potential anticancer drugs. Additionally, the review addresses specific gaps in our understanding of the field that may require further investigation.
Expert opinion
Targeting specific Ca2+ signaling cascades could disrupt normal cellular activities, making cancer therapy complex and elusive. Therefore, there is a need for improvements in current Ca2+ signaling pathway focused medicines. While synthetic molecules and plant compounds show promise, they also come with certain limitations. Hence, exploring the framework of targeted drug delivery, structure-rationale-based designing, and repurposing potential drugs to target Ca2+ transporting proteins could potentially lead to a significant breakthrough in cancer treatment.
Article highlights
Intracellular Ca2+ signaling alteration results in the promotion and progression of different types of cancer.
Targeting Ca2+-transporting proteins is an effective way to prevent cancer proliferation and progression.
The Ca2+ signaling toolkit has a significant role in activating apoptosis to regulate cancer menace.
Modulators of the Ca2+ signaling toolkit have demonstrated promise in targeting cancer.
Targeted drug delivery and drug repurposing are likely efficient approaches to tackle limitations in targeting specific Ca2+ transporting proteins.
Abbreviations
| AP-1 | = | Activator protein-1 |
| Ca2+ | = | Calcium ion |
| CACNA | = | Ca2+ voltage-gated channel subunit alpha |
| CaM | = | Calmodulin |
| CaMKII | = | Calcium calmodulin-dependent protein kinase II |
| CaN | = | Calcineurin |
| CDKIs | = | Cyclin-dependent kinase inhibitors |
| CTLA | = | Cytotoxic T lymphocyte-associated protein |
| CRAC | = | Calcium release-activated calcium |
| eEF2 | = | Eukaryotic elongation factor 2 |
| EMT | = | Epithelial to mesenchymal transitions |
| EPR | = | Enhanced permeability and retention |
| ER | = | Endoplasmic reticulum |
| ERK | = | Extracellular signal-regulated kinase |
| 5-FU | = | 5-fluorouracil |
| HIF-1α | = | Hypoxia-Inducible Factor-1α |
| IP3R | = | Inositol triphosphate receptor |
| LAG | = | Lymphocyte activation gene |
| MAPK | = | Mitogen activated protein kinases |
| MCU | = | Mitochondrial calcium uniporter |
| miR | = | microRNA |
| MLCK | = | Myosin light-chain kinase |
| MMP | = | Matrix metalloproteinase |
| MPT | = | Mitochondrial permeability transition |
| Mt | = | Mitochondria |
| NCX | = | Na+/Ca2+exchanger |
| NFAT | = | Nuclear factor of activated T cells |
| NFκB | = | Nuclear Factor Kappa-light-chain-enhancer of activated |
| PM | = | Plasma Membrane |
| PCD | = | Programmed cell death |
| PLCƴ | = | Phospholipase C-ƴ |
| PMCA | = | Plasma membrane Ca2+-ATPase |
| PML | = | Promyelocytic leukemia protein |
| PSMA | = | Prostate-specific membrane antigens |
| PTEN | = | Protein phosphatase and tensin homolog |
| PTT | = | Photothermal therapy |
| RB1 | = | Retinoblastoma1 |
| RyRs | = | Ryanodine receptors |
| SERCA | = | Sarco-endoplasmic reticulum calcium transport ATPase |
| SOCC | = | Store operated calcium channel |
| SPCA | = | Secretory pathway Ca2+/Mn2+-ATPase |
| STIM1 | = | Stromal interacting molecule 1 |
| TG | = | Thapsigargin |
| TME | = | Tumor microenvironment |
| TRP | = | Transient receptor potential |
| VDAC | = | Voltage-dependent anion channel |
| VEGF | = | Vascular endothelial growth factor |
| VGCC | = | Voltage-gated Ca2+ channels |
Acknowledgments
The authors acknowledge the support of the Director of the CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, for providing the necessary research facilities.
Declaration of interest
J Singh declares receiving a Senior Research Fellowship from the Council of Scientific and Industrial Research (CSIR), New Delhi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.