Calcium channel blockers potentiate gemcitabine chemotherapy  in pancreatic cancer

Principe, Daniel R.; Aissa, Alexandre Ferro; Kumar, Sandeep; Pham, Thao N.D.; Underwood, Patrick W.; Naveed, Ammara; Ke, Rong; Rana, Basabi; Treviño, José G.; Munshi, Hidayatullah G.; Benevolenskaya, Elizaveta V.; Rana, Ajay

doi:10.1073/pnas.2200143119

Cited by 21 publications

(8 citation statements)

References 59 publications

(77 reference statements)

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“…Several existing chemotherapeutic agents such as cisplatin, can modify intracellular Ca 2+ , prompting tumor cell apoptosis [ 42 ]. Furthermore, the calcium signaling pathway significantly contributes to drug resistance in tumors [ 43 ]. Consequently, proteins that regulate Ca 2+ such as transmembrane cation channels, hold promise as potential targets for cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

The development of prognostic gene markers associated with disulfidptosis in gastric cancer and their application in predicting drug response

Liu,

2024

Heliyon

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Section: Discussionmentioning

confidence: 99%

The development of prognostic gene markers associated with disulfidptosis in gastric cancer and their application in predicting drug response

Liu,

2024

Heliyon

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“…In a retrospective cohort study, the authors concluded that CCBs may prolong survival in PC patients [30]. Principe et al (2022) [31] used CCBs, such as amlodipine, which inhibited pro-survival extracellular signal-regulated kinase (ERK) signaling in vitro and remarkably enhanced therapeutic responses to gemcitabine in both orthotopic xenografts and transgenic PC models. Further prospective studies are required to establish the exact impact of anti-hypertensive treatment on PC patient survival.…”

Section: Discussionmentioning

confidence: 99%

The prevalence and impact of overweight and hypertension among patients with pancreatic cancer

Fudalej,

Cichowska,

Badowska-Kozakiewicz

et al. 2024

Oncol Clin Pract

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Introduction. Pancreatic cancer (PC) remains one of the most deadly malignancies with rising incidence. As therapeutical options seem unsatisfactory, great effort should be put into identifying and reducing risk factors as well as distinguishing possible factors influencing patient outcomes. The study aimed to describe the prevalence of overweight and hypertension among PC patients, analyse the possible association between overweight, hypertension and clinicopathological factors and distinguish variables influencing survival. Material and methods. A retrospective analysis of medical records was performed. The study was designed in two branches: (1) the comparison of patients with hypertension (HTN group) and without;(2) the comparison of patients with BMI ≥ 25 and patients with BMI < 25. Statistical analysis with the usage of appropriate tests was conducted. Results. No differences in survival between studied groups in the two branches were determined, even after subdividing into adjuvant and palliative types of treatment. Patients with HTN were more likely to be older, have diabetes and be diagnosed without distant metastases. BMI, ACEIs/ARBs use, diabetes, CRP/lymphocyte ratio (CLR) and AJCC IIb stage influenced survival. Patients with overweight/obesity were more likely to have an autoimmune disease, metastases in ≥ 4 lymph nodes (N2), tumour size between 2 and 4 cm (T2) and experience neutropenia as side effect of palliative chemotherapy. Higher BMI and CRP level influenced survival. Conclusions. The exact effect of ACEIs/ARBs on cancerogenesis should be further studied. CLR appears to be a feasible marker for prognosis in PC.

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“…In contrast, our experiments with gemcitabine are in line with the role of TRPV6 as a Ca 2+ channel. Gemcitabine toxicity is activated by the blockage of calmodulin pathways [36]. The knockdown of TRPV6 can lead to lower levels of calmodulin activation and thereby increase the cytotoxicity of gemcitabine action in PDAC cells [27].…”

Section: Discussionmentioning

confidence: 99%

TRPV6 Channel Is Involved in Pancreatic Ductal Adenocarcinoma Aggressiveness and Resistance to Chemotherapeutics

Mesquita,

Haustrate,

Mihalache

et al. 2023

Cancers

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Pancreatic ductal adenocarcinoma (PDAC) stands as a highly aggressive and lethal cancer, characterized by a grim prognosis and scarce treatment alternatives. Within this context, TRPV6, a calcium-permeable channel, emerges as a noteworthy candidate due to its overexpression in various cancers, capable of influencing the cell behavior in different cancer entities. Nonetheless, the exact expression pattern and functional significance of TRPV6 in the context of PDAC remains enigmatic. This study scrutinizes the expression of TRPV6 in tissue specimens obtained from 46 PDAC patients across distinct stages and grades. We manipulated TRPV6 expression (knockdown, overexpression) in the human PDAC cell lines Panc-1 and Capan-1. Subsequently, we analyzed its impact on multiple facets, encompassing Ca2+ influx, proliferation, apoptosis, migration, chemoresistance, and tumor growth, both in vitro and in vivo. Notably, the data indicate a direct correlation between TRPV6 expression levels, tumor stage, and grade, establishing a link between TRPV6 and PDAC proliferation in tissue samples. Decreasing TRPV6 expression via knockdown hampered Ca2+ influx, resulting in diminished proliferation and viability in both cell lines, and cell cycle progression in Panc-1. The knockdown simultaneously led to an increase in apoptotic rates and increased the susceptibility of cells to 5-FU and gemcitabine treatments. Moreover, it accelerated migration and promoted collective movement among Panc-1 cells. Conversely, TRPV6 overexpression yielded opposing outcomes in terms of proliferation in Panc-1 and Capan-1, and the migration of Panc-1 cells. Intriguingly, both TRPV6 knockdown and overexpression diminished the process of tumor formation in vivo. This intricate interplay suggests that PDAC aggressiveness relies on a fine-tuned TRPV6 expression, raising its profile as a putative therapeutic target.

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Calcium channel blockers potentiate gemcitabine chemotherapy in pancreatic cancer

Cited by 21 publications

References 59 publications

The development of prognostic gene markers associated with disulfidptosis in gastric cancer and their application in predicting drug response

The development of prognostic gene markers associated with disulfidptosis in gastric cancer and their application in predicting drug response

The prevalence and impact of overweight and hypertension among patients with pancreatic cancer

TRPV6 Channel Is Involved in Pancreatic Ductal Adenocarcinoma Aggressiveness and Resistance to Chemotherapeutics

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