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Introduction
As indicated in GLOBOCAN 2020, PanCa is the 12th most common cancer, ranking 7th (4.7%) in terms of global cancer associated mortality. PanCa is one of the tumors with the worst prognosis, and unlike other cancers, few advances have been made in recent years. The only curative option is surgery, but only 15–20% of patients are candidates, with a high risk of relapse. In advanced PanCa there are few first-line treatment options, however, no validated biomarkers for better treatment selection have been identified so far[1, 2, 3–4]. As, standard treatment options of PanCa are mostly inefficient, a finer understanding of the disease pathophysiology is indispensable for efficient disease management.
Ion channels are transmembrane pore-forming proteins, contributing substantially to “hallmarks of cancer”. These ubiquitous proteins with altered expression in cancer, facilitate inward or outward flow of ions, accordingly modifying cellular bio-chemical and electrical properties, ultimately influencing signaling networks associated with gene expression and inter-organellar dialogues [5, 6]. They modify microenvironmental cues, contributing to PanCa aggressiveness through excessive fibrosis, immune invasion, metastasis and drug/ chemo resistance [7, 8]. Several potassium channels overexpressed in PanCa are: (i) inward potassium channel, Kir3 [9]. (ii) calcium activated potassium channel, KCa3.1[10] (iii) two-pore domain containing K+ channel, TWIK-1 and TASK-2, (iv) voltage-gated K + channels, Kv1.3 Kv1.5 and Kv11.1[11, 12–13] and (v) potassium calcium-activated channel subfamily N member 4, KCNN4. Kv10.1, absent in normal pancreas is expressed in PanCa, while Kv7.1 and KCNE1 are suppressed in pancreatic ductal adenocarcinoma (PDAC) Chloride channels (CLICs) elevated in PanCa cell lines and tumor samples are (i) CLIC1, CLIC2, and CLIC3 (ii) calcium activated chloride channel, anoctamin 1 (ANO1) and (iii) TMEM16A and TMEM16J. [11] While (i) CLIC5) (ii) calcium activated chloride channel, CLCA-1[14] (iii) chloride channel Kb (CLCNKB) and chloride voltage-gated channel 1 (CLCN1) are inhibited in PDAC. Calcium channels, overexpressed in PDAC are (i) transient receptor potential (TRP) channels, TRPM2, TRPM7, TRPM8, TRPC1, TRPC4, and TRPC6 (ii) voltage-dependent calcium channels, CaV2.1 and ORAI1 [15] TRPM8 facilitates cell-cycle, proliferation and invasion; while inhibits replicative senescence, thereby contributing in pancreatic neoplasm pathogenesis [16]. However, the molecular mechanism and their precise role in PanCa are still blurred.
In this article, the substantially...