Transient receptor potential channels in multiple myeloma
Lingjun Meng1, Guiying Gu1, Lintao Bi1
1Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Abstract:
Multiple myeloma is the second most commonly diagnosed hematologic malignancy. As an incurable disease, the molecular mechanisms underlying its many aspects remain unclear. Intracellular calcium ion is an essential signaling molecule that modulates malignant cell behavior, and abnormal regulation of cellular calcium homeostasis may promote cancer cell survival and induce drug resistance. Transient receptor potential (TRP) cation channels are a superfamily of non-selective Ca2+-permeable channels that regulate intracellular calcium signaling and are involved in the regulation of various characteristics of cancer cells. Emerging evidence shows a close connection between TRP channels and multiple myeloma. This review summarizes the roles of TRP channels in multiple myeloma progression, metastasis, bone destruction, and drug resistance. TRPV1 and TRPV2 orchestrate the progression of multiple myeloma, while TRPM7 promotes myeloma cell dissemination and spreading. TRPV2 and TRPV4, that activate osteoclasts, contribute to the development of osteolytic bone disease caused by multiple myeloma. Both TRPV1 inhibition and TRPV2 activation synergize with bortezomib in the chemotherapy of multiple myeloma, and TRPC1 can determine the responsiveness of multiple myeloma to MTI-101, a cyclic beta-hairpin peptide. Antagonizing TRPA1 can alleviate bortezomib-induced painful peripheral neuropathy. Future studies in this field may identify certain TRP channels as markers or therapeutic targets for predicting the prognosis, preventing progression, and improving drug responsiveness in patients with multiple myeloma.
Insights
Transient Receptor Potential (TRP) channels are crucial in multiple myeloma, influencing cancer progression, bone destruction, and drug resistance. Targeting these calcium channels offers potential therapeutic strategies for this incurable hematologic malignancy.
Area of Science:
- Oncology
- Molecular Biology
- Calcium Signaling
Background:
- Multiple myeloma is a prevalent, incurable hematologic malignancy with incompletely understood molecular drivers.
- Intracellular calcium ions are key signaling molecules; dysregulated calcium homeostasis promotes cancer survival and drug resistance.
- Transient Receptor Potential (TRP) channels, critical regulators of calcium signaling, are implicated in various cancer cell behaviors.
Purpose of the Study:
- To review the multifaceted roles of TRP channels in multiple myeloma.
- To explore TRP channel involvement in disease progression, metastasis, bone destruction, and drug resistance.
- To identify potential TRP channel-based therapeutic targets and prognostic markers.
Main Methods:
- Literature review synthesizing current research on TRP channels in multiple myeloma.
- Analysis of studies detailing specific TRP channel functions (e.g., TRPV1, TRPV2, TRPM7, TRPV4, TRPC1, TRPA1).
- Examination of evidence linking TRP channels to clinical outcomes and therapeutic responses.
Main Results:
- TRPV1 and TRPV2 channels drive multiple myeloma progression.
- TRPM7 promotes cancer cell dissemination, while TRPV2 and TRPV4 contribute to myeloma-associated bone destruction.
- TRP channel modulation shows promise in enhancing chemotherapy (e.g., TRPV1 inhibition, TRPV2 activation with bortezomib) and predicting drug response (TRPC1 with MTI-101).
- TRPA1 antagonism may mitigate bortezomib-induced neuropathy.
Conclusions:
- TRP channels are integral to multiple myeloma pathogenesis and clinical characteristics.
- Specific TRP channels represent promising therapeutic targets for multiple myeloma treatment.
- TRP channel activity may serve as biomarkers for prognosis and drug responsiveness in multiple myeloma patients.
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