Calcium Influx Pathways in Breast Cancer: Opportunities for Pharmacological Intervention


Austin J Pharmacol Ther. 2023; 11(3): 1179.

“Calcium Influx Pathways in Breast Cancer: Opportunities for Pharmacological Intervention”

Hari Sonwani*

Apollo College of Pharmacy, Anjora, Durg, India

*Corresponding author: Hari Sonwani Apollo College of Pharmacy, Anjora, Durg, India. Email: [email protected]

Received: November 06, 2023 Accepted: December 07, 2023 Published: December 14, 2023


Numerous cellular processes, including the release of neurotransmitters and the contraction of muscles, are largely triggered and regulated by Ca2+ inflow via Ca2+ permeable ion channels. In addition, Ca2+ influx regulates cellular migration and proliferation, two mechanisms linked to cancer. This study focuses on calcium influx in breast cancer cells and discusses how future drugs for breast cancer therapy may be pharmacological modulators of particular Ca2+ influx channels. Certain breast tumors have altered expression of particular calcium permeable ion channels. Such alterations may occasionally be connected to the prognosis and subtype of breast cancer. These days, models both in vivo and in vitro have assisted in identifying particular Ca2+ channels that are crucial for the growth and invasiveness of of cancerous breast cells. Nonetheless, additional research is still needed to fully understand several features of Ca2+ influx in breast cancer. These include figuring out the processes behind the changed expression and the best treatment plan to target breast cancer cells via particular Ca2+ channels. In the upcoming ten years, research should concentrate on the function of Ca2+ influx in mechanisms other than the migration and proliferation of breast cancer cells.

Keywords: Breast cancer; Calcium channels; Calcium influx; Calcium signalling; Oncology

Abbreviations: N-cyano-N"-[(1S)-1-phenylethyl]; [Ca2+]CYT, cytoplasmic-free calcium; IP3, inositol 1,4,5-trisphosphate; JNJ41876666, 3-[7-trifluoromethyl-5- (2-trifluoromethyl-phenyl)]; ErbB2 (also known as HER2), human EGF receptor 2; EC, endothelial cells; EMT, epithelial to mesenchymal transition; ER+, oestrogen positive; ERa, oestrogen receptor a;Azol-2-yl-1H-benzimid[4.5]dec -1-oxa-2-aza-spiro2-eneHydrochloride; NNC 55-0396, (1S,2S); NFAT, nuclear factor for activated T-cells[(3-benzimidazol-2-yl)propyl] -2-(2-(N-]The methylamino)ethyl grouptetrahydro-6-fluoro-1,2,3, 4-Pyr3, 1-[4-[(2,3,3-trichloro-1-oxo-2-propen-1-yl)amino]phenyl]; PMCA, plasma membrane Ca2+-ATPase; -1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochlorideTrifluoromethyl, or 5-4-carboxylic acid pyrazole -1H; SCID stands for severe combined immune deficiency; SB-209712 is 1,6,bis{1-[4-(3-phenylpropyl) piperidinyl]}hexane; transient receptor potential; TRP, secretory route Ca2+-ATPase


With intracellular free Ca2+ levels almost 20 000 times lower than in the external environment (100 nM vs. 1.8 mM), cells maintain a significant gradient of free Ca2+ across the plasma membrane (Carafoli, 1987; Clapham, 2007). Utilizing this Ca2+ gradient, cells frequently use Ca2+ influx to start and control cellular signals, typically by opening Ca2+ permeable ion channels. Numerous varied routes are regularly muscle contraction, gene transcription, cell division, and neurotransmitter release are all triggered by increases in intracellular cytoplasmic-free calcium ([Ca2+]CYT) [14]. For a number of ailments, Ca2+ permeable ion channels may be useful pharmacological targets. Among these disorders include hypertension, for which nifedipine and other L-type voltage-gated Ca2+ channel blockers are used clinically [5], and chronic pain. Ziconotide, an N-type channel inhibitor, is employed (Malmberg and Yaksh, 1995). The research that has evaluated calcium influx routes in the development of breast cancer and identified calcium permeable ion channels as pharmacological targets for breast cancer therapy will be the main emphasis of this review.

Calcium Signaling: The Critical Function of Calcium Influx

Numerous reviews [14 Leybaert and Sanderson, 2012) describe how mammalian cells control [Ca2+]CYT levels and the significance of the nature of variations in [Ca2+]CYT (such as [Ca2+]CYT oscillations and localized changes in Ca2+). As Figure 1 showsa few of the primary calcium exchangers, pumps, and channels in the pathways that signal calcium. In summary, the active efflux of Ca2+ from the cell through the plasma membrane Ca2+-ATPases (PMCAs) maintains [Ca2+]CYT levels at low levels. Activation of these enzymes, together with Na+/Ca2+ exchangers and sarco/endoplasmic reticulum Ca2+ ATPases, lowers [Ca2+]CYT. There are various mechanisms that can lead to increases in [Ca2+]CYT. For instance, several GPCRs, via means of activation of Through IP3-activated Ca2+ channels, PLC and the production of inositol 1,4,5-trisphosphate (IP3) release Ca2+ from internal calcium reserves, such as the sarco/endoplasmic reticulum [14]. The recently discovered mitochondrial Ca2+ uniporter (Kirichok et al., 2004) and the Na+/Ca2+ exchanger NCLX (Palty et al., 2010) are two more organelles that are involved in Ca2+ signaling. and the Golgi, which uses the secretory route Ca2+-ATPases (SPCAs) to sequester intracellular Ca2+. The opening of calcium permeable ion channels on the plasma membrane also results in increases in [Ca2+]CYT. Many distinct physiological activities, especially those involving excitable cells, such the release of neurotransmitters in neurons and the excitation–contraction coupling in skeletal muscle (Rios and Brum, 1987) [26], depend critically on calcium influx. (Tsien et al., 1988). In cells in the epithelium, calcium influx is also crucial for processes like the intestinal epithelial cells' absorption of Ca2+ [7,61]. We will give a quick summary of the many kinds of calcium permeable materials in the next section of this review.

Citation: Hari Sonwani. Calcium Influx Pathways in Breast Cancer: Opportunities for Pharmacological Intervention. Austin J Pharmacol Ther. 2023; 11(3): 1179.