Targeting T-type channels in cancer: What is on and what is off?

T-type channels in cancer cells: Driving in reverse

“…In contrast to voltage-gated channels, multiple types of voltageindependent Ca 2+ channels are consistently upregulated in many cancer cells/tissues, in which they promote the activation of biochemical cascades emanating from Ca 2+ -calmodulin (CaM). For instance aberrant expression of TrpC, TrpM, TrpV and store-operated ORAi channels has been shown to positively regulate small GTPase Ras-mitogen-activated protein kinases (MAPKs), serine/threonine protein kinase B/AKT or calcineurin phosphatase [1,15], all pathways common to TTCCs activity [54]. Akin to TTCCs, some of the above-mentioned channels have also been reported to interact with KCa channels, thus feeding back on their own activity [55].…”

Modulation of FDG Uptake by Cell Cycle Synchronization Using a T-Type Calcium Channel Inhibitor

“…As prostate-specific membrane antigen (PSMA) is overexpressed in most prostate cancers, radiolabeled PSMA shows higher diagnostic sensitivity in detecting lymph node and distant metastasis, recurrences, and intraoperative tumor localization than other imaging modalities [11]. A few radiotracers that perform better than 18 F-FDG have been documented in hepatocellular carcinoma. Of these, acetate, a precursor of phosphatidylcholine, exhibits high sensitivity, especially for well-differentiated tumors [12].…”

“…Of these, acetate, a precursor of phosphatidylcholine, exhibits high sensitivity, especially for well-differentiated tumors [12]. 11 C-acetate and 18 F-FDG have complementary roles in the detection of hepatocellular carcinoma. In a previous study with gastric signet ring cell carcinoma, radiolabeled fibroblast-activating protein inhibitors showed higher radiotracer uptake than 18 F-FDG and thus were more sensitive for detecting the primary tumor, lymph node metastasis, and local recurrence [13]; however, these radiopharmaceuticals cannot replace FDG because of the wide availability of FDG and the ability of FDG to detect other malignancies [7,14].…”

“…11 C-acetate and 18 F-FDG have complementary roles in the detection of hepatocellular carcinoma. In a previous study with gastric signet ring cell carcinoma, radiolabeled fibroblast-activating protein inhibitors showed higher radiotracer uptake than 18 F-FDG and thus were more sensitive for detecting the primary tumor, lymph node metastasis, and local recurrence [13]; however, these radiopharmaceuticals cannot replace FDG because of the wide availability of FDG and the ability of FDG to detect other malignancies [7,14]. Therefore, these specific radiopharmaceuticals can only be used to supplement FDG, which would make the assessment process more time-consuming and costly.…”

“…Consequently, the sensitivity of FDG PET itself must be improved. Our hypothesis is that enhancing the sensitivity of 18 F-FDG in these tumors through a simple preparation would be better than using multiple diagnostic tests.…”