TRPC6 (Transient Receptor Potential Cation Channel Subfamily C Member 6)

P3, N=286, Recruiting, Boehringer Ingelheim | Not yet recruiting --> Recruiting

The TRPC6 A404V is a gain-of-function variant that exhibits enhanced activity in the presence of doxorubicin. Therefore, the TRPC6 A404V variant represents a risk factor for anthracycline-induced cardiotoxicity in patients with cancer.

Gain-of-function mutations in the transient receptor potential 6 (TRPC6) channel have recently been recognized as risk factors for both doxorubicin (DOX)-induced cardiomyopathy...Importantly, the results obtained from molecular docking and patch clamp recordings were strongly correlated, showing an 82% concordance, higher than the predictions from AlphaMissense. These findings indicate that our computational analysis provides a rapid and reliable method for predicting the functional impact of TRPC6 missense variants, which may aid clinical decision-making in cancer patients receiving chemotherapy.

In this study, a CIPN mouse model with emotional disorders was established through the intervention of cisplatin for 21 d, which was validated by the von Frey test, adhesive removal test, open-field test and elevated plus-maze test...Mechanically, EA treatment significantly inhibited TRPC6 activation, reducing the Ca2+ influx and attenuating p-PKC level, thereby decreasing the release of excitatory neurotransmitter glutamate in the PVT. Our findings revealed a novel mechanism through which calcium influx-mediated glutamatergic neuron activation in PVT participated in the CIPN and provided evidence that TRPC6/PKC may be potent targets for the EA effect.

Importantly, treatment of TNBC cells with a TRPC6 inhibitor reduces metastasis significantly, an effect that is mitigated by a ferroptosis inhibitor. These results indicate that a sub-population of TNBC cells characterized by TRPC6 expression has the potential to form metastases by evading ferroptosis.

In contrast to published researches, we found that TRPC6 expression was negatively correlated with breast cancer cell proliferation and metastasis abilities, suggesting TRPC6 as a promising prognostic biomarker for breast cancer, where low expression of TRPC6 was related to worse prognoses. This research raises the necessity of rethinking the mechanism perspective and targetability of TRPC6 in breast cancer, which warrants further investigation.

Furthermore, bendamustine-induced ER stress, shown by upregulated Chop expression, suggests that ER stress plays a role in its anticancer activity. These findings highlight bendamustine as a promising therapeutic agent for breast cancer treatment.

Our results elucidate that axitinib induces podocyte filtration barrier core protein loss, foot process effacement, glomerulosclerosis, and proteinuria through upregulation of TRPC6 protein expression. Additionally, naturally derived luteolin serves as a potential intervention strategy, providing a theoretical basis for the clinical prevention and treatment of nephrotoxicity caused by axitinib and other TKIs.

In last decade many natural, semi synthetic and synthetic pharmaceutical agents modulating TRPC6 activity have been investigated which can be alucrative approach for the prevention and treatment of diseases associated with TRPC6 channel downregulation and upregulation. Therefore, present review aims to summarize the involvement of TRPC6 with its Ca2+ dependent effect in different physiological and pathological conditions with the downregulation as well as upregulation of TRPC6 channel functions and summarizes the progress achieved in those investigations pertaining to modulators of TRP6 channels.

Molecular docking further identified dexamethasone and levonorgestrel as potential modulators of these targets, paving the way for personalized meningioma treatment strategies. This research advances our understanding of meningioma's molecular landscape and illustrates the power of genomic and transcriptomic integration in the realm of precision oncology.

P2, N=67, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

TRPC6 expression correlated strongly with immune cell infiltration, immune checkpoint genes, and sensitivity to therapies such as Lapatinib, anti-CTLA4, and anti-PD1 treatments...This study highlights the prognostic significance of TRPC6 in STAD and its potential as a therapeutic target. TRPC6's involvement in immune regulation and cancer cell progression underscores its dual role in STAD pathogenesis and treatment, offering new avenues for targeted therapy development.