However, the development of TRPV6 inhibitors is still in the early stage, and the existing TRPV6 inhibitors have poor selectivity and off-target effects. In this review, we focus on summarizing and describing the structure characters, and mechanisms of existing TRPV6 inhibitors to provide new ideas and directions for the development of novel TRPV6 inhibitors.

NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.

Several pieces of evidence suggest that it is upregulated in the advanced stages of thyroid, ovarian, breast, colon, and prostate cancers. The function of TRPV6 in regulating calcium signaling in cancer will be covered in this review, along with its potential applications as a cancer treatment target.

Yet, mutation of the cytosolic pore exit reduced inhibition by cis-22a but preserved sensitivity to PIP depletion. Our data underscore allosteric communication between the lipid binding site and the pore and vice versa for most sites along the pore.

The knockdown simultaneously led to an increase in apoptotic rates and increased the susceptibility of cells to 5-FU and gemcitabine treatments...Intriguingly, both TRPV6 knockdown and overexpression diminished the process of tumor formation in vivo. This intricate interplay suggests that PDAC aggressiveness relies on a fine-tuned TRPV6 expression, raising its profile as a putative therapeutic target.

Inhibitors of this oncochannel are therefore particularly needed. In this review, we provide an overview of recent advances in structural pharmacology that uncovered the molecular mechanisms of TRPV6 inhibition by a variety of small molecules, including synthetic and natural, plant-derived compounds as well as some prospective and clinically approved drugs.

No abstract available

RNA-seq analysis demonstrated that the calcium channel TRPV6, being a crucial player of calcium signaling, significantly impacts the expression of genes involved in cancer progression, such as cell cycle regulation, chemotaxis, migration, invasion, apoptosis, ferroptosis as well as drug resistance, and extracellular matrix (ECM) re-organization. Our data suggest that the trpv6 gene is involved in and regulates multiple pathways related to tumor progression and drug resistance in castration-resistant prostate cancer cells.

Describing CBP-1008: a FR/ TRPV6 targeted drug conjugate in Phase II pivotal studies of advanced ovarian cancer treatment; Exploring CBP-1018: a FR/ PSMA targeted drug conjugate in Phase Ib for prostate cancer therapy; Highlighting CBP-1019: TOP1i payload drug conjugate for unmet medical needs

P1, N=11, Completed, M.D. Anderson Cancer Center | Recruiting --> Completed | N=36 --> 11

Moreover, all TUNEL-positive cells had TRPV6 membrane staining as compared to the control antibody treatment where TRPV6-positive cells were all TUNEL negative. These data clearly demonstrate that TRPV6 channel targeting using rb79 and rb82 antibodies is fatal and may be successfully used in the anticancer therapies.

Finally, DFMO treatment enhanced the transcription of the PMCA4 Ca pump and mitochondrial channels MCU and VDAC3 for enhanced Ca extrusion through the plasma membrane and mitochondria. Collectively, these findings suggested the critical role of polyamines in Ca remodeling in colorectal cancer.

Using prostate cancer resection specimens, we have confirmed the absence of the TRPV6 protein in both healthy and benign hyperplasia, as well as its expression and correlation to the prostate cancer grades. Thus, the generated rabbit polyclonal anti-TRPV6 channel antibody rb79 is suitable for all in vitro diagnostic applications and particularly for the diagnosis in clinics using paraffin-embedded sections from patients suffering from various diseases and disorders involving the TRPV6 channel.

P1, N=36, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2022 --> Aug 2023 | Trial primary completion date: Aug 2022 --> Aug 2023

The expression levels were correlated with the tumoral stages and are related to the genes involved in calcium homeostasis (Calbindin 1 or S100A4) or to proteins participating in metastasis (PTPN1). We conclude that the selected TRP proteins provide new insights in the search for targets and biomarkers needed for therapeutic strategies for PDAC treatment.

Within the FRα+/TRPV6+ tumors, tumor growth inhibition well correlates with IHC score of FRα (R2=0.89).It is indicated that clinical trials in selected indications using biomarkers assay to screening patients will expedite the clinical development of CBP-1008. Initial clinical response has been observed in our Phase I trial.

Zinc signaling suppresses VDR-induced expression of CDH1.

GJB2 and SCNN1B were identified as prognostic biomarkers and therapeutic targets for LUAD.

In conclusion, ATP1A2, MT1M, SLC6A19 and TRPV6 may be contributing to absorption of metals in PM thereby inducing apoptosis mediated by ROS. Therefore, they hold potential as therapeutic targets for PM-related diseases.

The results indicate that TRPV6 may promote prostate cancer progression in association with MMP9 and cathepsin B, thereby validating further research into TRPV6 as a useful therapeutic target for local invasion or metastasis of advanced prostate cancer.

Also, endoplasmic reticulum (ER) stress markers BiP, CHOP, p-SAPK, and p-eIF2α levels were increased by CSE treatment. These results suggest that CSE may increase the concentration of intracellular calcium, thus increasing mitochondrial and ER stress.

This reversible HS/ML in vitro system might help in understanding the pathophysiological impact of the transportome in the dedifferentiation process in pancreatic carcinogenesis. Furthermore, the HS/ML model represents a novel system for studying the role of the transportome during the switch from a more benign, differentiated (HS) to a highly malignant, undifferentiated (ML) phenotype.

TSA suppresses cervical cancer cell proliferation and induces apoptosis and autophagy through regulation of the PRMT5/STC1/TRPV6/JNK axis.

Furthermore, expression level of TRPV6 was tightly linked to the levels of common EMT markers, suggesting that TRPV6 may have a role in the mesenchymal invasion of breast cancer cells. Thus, either too low or too high TRPV6 levels compromise homeostasis of the mammary epithelial sheets and may promote the progression of pathophysiological conditions.

This is the first study to suggest the independent prognostic value of certain proteins involved in Ca influx in systemic recurrence after RP: overexpression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 is associated with a lower risk of systemic recurrence. TRPC4, TRPV5, and TRPV6 appear to be particularly interesting, as they are independent of the five commonly used predictive factors, that is, PSA, percentage of positive biopsies, SM status, Gleason score, and pT stage.

Moreover, the result of transcriptome analysis of the colon tissue suggested that BSH-1 normalized the expression of genes related to GI peristalsis (i.e. Ache, Chrm2, Chrm3, Slc18a3, Grp, Htr3a, Htr4, Vip, Vipr, Apoa4 and Lepr), colonic water and ion transport (i.e. Aqp4, Aqp8, Atp12a, Adcy2, Adcy8 and Trpv6), intestinal inflammation (i.e. Cyp2d12, Muc2, Muc3, Lbp, Lgals2, Nos2 and Nox1) and intestinal cancer (i.e. Bcl2, Bcl2l15, Gsdmc2, Gsdmc4, Ntn1, Olfm4, Pitx2, Reg4, Saa3 and Wnt2b). The above results indicated that BSH-1 consumption effectively ameliorated loperamide-induced constipation in mice and could be suggested as a functional food choice for constipation.