TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer

Abstract

Breast cancer is one of the most frequent cancer types worldwide and the first cause of cancer-related deaths in women. Although significant therapeutic advances have been achieved with drugs such as tamoxifen and trastuzumab, breast cancer still caused 627,000 deaths in 2018. Since cancer is a multifactorial disease, it has become necessary to develop new molecular therapies that can target several relevant cellular processes at once. Ion channels are versatile regulators of several physiological- and pathophysiological-related mechanisms, including cancer-relevant processes such as tumor progression, apoptosis inhibition, proliferation, migration, invasion, and chemoresistance. Ion channels are the main regulators of cellular functions, conducting ions selectively through a pore-forming structure located in the plasma membrane, protein–protein interactions one of their main regulatory mechanisms. Among the different ion channel families, the Transient Receptor Potential (TRP) family stands out in the context of breast cancer since several members have been proposed as prognostic markers in this pathology. However, only a few approaches exist to block their specific activity during tumoral progress. In this article, we describe several TRP channels that have been involved in breast cancer progress with a particular focus on their binding partners that have also been described as drivers of breast cancer progression. Here, we propose disrupting these interactions as attractive and potential new therapeutic targets for treating this neoplastic disease.

Comprehensive Analysis of TRP Channel-Related Genes for Estimating the Immune Microenvironment, Prognosis, and Therapeutic Effect in Patients With Esophageal Squamous Cell Carcinoma

“…The TME has a vital regulatory effect on carcinogenesis and tumor progression (Lin et al, 2016). TRP channels may have an impact on the TME by regulating the interactions between the sensory-vascular-immune-tumor systems (Khalil et al, 2018;Saldías et al, 2021). Based on our scoring system, there was notable diversity in the TME between the low-risk and high-risk groups.…”

Repurposing hyperpolarization‐activated cyclic nucleotide‐gated channels as a novel therapy for breast cancer

“…Overexpression of various TRP channels has been suggested to associate with poorer outcome of breast cancer. 45 TRP channels are responsible for mediating the import of calcium ions. Therefore, targeting TRP channels could be an alternative for targeting calcium signalling to compromise the survival advantage of breast cancer cells.…”

The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

“…Several keynote factors such as hypoxia, elevated oxidative stress, abnormal redox state, and altered mechanical stretch force contribute to the dysregulated expression of TRP channels. The TRP channel expression in various cancer types and the modulators that have already or will enter the clinic is discussed in Table 1 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 .…”