Repurposing calcium channel blockers: may be sensible combination with erlotinib for non-small cell lung cancer

Alandağ, Celal; Merev, Elif; Özdemir, Feyyaz

doi:10.1097/cad.0000000000001098

Cited by 3 publications

(3 citation statements)

References 9 publications

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“…The 1-year OS rate for CCB users and nonusers was 78.3% and 39.7%, respectively, whereas the 2-year PFS rate was 44.4% and 8.3%, respectively. 19 Our study showed similar results, with the estimated median PFS and OS for the CCBs-/EGFR-TKIs + group being 7.70 and 12.17 months, respectively; the results were significantly different from those of the CCBs + /EGFR-TKIs + group (10.43 and 18.07 months, respectively). Therefore, concomitant use of CCBs and EGFR-TKIs can improve PFS and OS.…”

Section: Discussionsupporting

confidence: 80%

Survival Outcomes of Calcium Channel Blocker Therapy in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Inhibitors: A Retrospective Study

Hsieh

Chen

et al. 2023

Integr Cancer Ther

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Background: Non-cancer drugs are currently being repurposed for cancer treatment. Mounting evidence highlights the influence of calcium channels on tumorigenesis and progression. Hence, inhibition of calcium signaling may be a promising cancer treatment strategy. Objective: In this study, we aimed to examine whether calcium channel blockers (CCBs) affect the efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). Design: We conducted a retrospective analysis. Methods: In this study, conducted between January 2009 and June 2021, patients with NSCLC treated with erlotinib, or gefitinib for at least 1 week were enrolled and divided into 2 groups: CCBs-/EGFR-TKIs+ and CCBs+/EGFR-TKIs+, depending on whether they received CCB therapy. Progression-free survival (PFS) and overall survival (OS) were determined as the primary and secondary endpoints, respectively. Result : The estimated median PFS and OS for the CCBs-/EGFR-TKIs+group were 7.70 and 12.17 months, respectively, and they were significantly different from those of the CCBs+/EGFR-TKIs+ group (10.43 and 18.07 months, respectively). CCB use was associated with improved PFS (adjusted hazard ratios [HR] 0.77, 95% confidence interval [CI]: 0.61-0.98; P = .035) and OS (adjusted HR 0.66, 95% CI: 0.51-0.84; P < .001). Conclusion: Calcium channels have been implicated in cancer pathogenesis. Our findings revealed the potential additive anticancer effects of CCBs when used concomitantly with EGFR-TKIs. However, study limitations, including the retrospective nature and small number of patients, necessitate large-scale prospective studies on the therapeutic potential of CCB as an adjunctive therapy with EGFR-TKIs in patients with NSCLC.

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Section: Discussionsupporting

confidence: 80%

Survival Outcomes of Calcium Channel Blocker Therapy in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Inhibitors: A Retrospective Study

Hsieh

Chen

et al. 2023

Integr Cancer Ther

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“…They showed that amlodipine decreases PD-L1 expression posttranslationally by blocking intracellular calcium flux, and it also facilitates the autophagic degradation of PDL-1. In our previous study, we showed that amlodipine and erlotinib have additive effects in metastatic nonsmall cell lung cancer [15].…”

Section: Discussionmentioning

confidence: 99%

Amlodipine improves the outcomes of regorafenib in metastatic colorectal cancer

Alandağ

Karaman²,

Yüce³

2022

Anti-Cancer Drugs

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Regorafenib is a multikinase inhibitor. It is used for metastatic colorectal cancer (mCRC) treatment. It has a mild effect. Regorafenib outcomes, and side effects may vary across patients. This study was aimed to evaluate the factors that affect regorafenib outcomes in mCRC patients. We conducted a single-center and retrospective study. Fifty-six patients were included. All patients had received regorafenib for mCRC. Some clinical and pathological factors and the effects of these factors on overall survival (OS), progression-free survival (PFS), and disease control rates (DCR) were analyzed. Concomitant amlodipine intake with regorafenib improved OS [14.26 vs. 6.97 months; 95% confidence interval, 4.04-20.84; P = 0.031] and DCR at 12th week (90% vs. 46%; P = 0.012). Hepatic metastasis was found as the poorest prognostic factor in both univariate and multivariate analyses. Patients who received chemotherapy after regorafenib had better OS. Good performance status was the strongest indicator of better OS. Patients taking amlodipine for arterial hypertension at the same time with regorafenib had numerically better OS and PFS and statistically better DCR. Amlodipine itself already has anticancer effects, and it has additive anticancer effects with regorafenib. The presence of hepatic metastases was found to be the most important prognostic factor for OS. There were not any predictive factors of side effects to regorafenib.

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“…In our previous retrospective studies, we have shown that especially regorafenib and amlodipine combination increases the effectiveness at colorectal cancer [2]. In out another study, we showed that amlodipine inproves outcomes of erlotinib in non-small cell lung cancer [3]. In preclinical studies, amlodipine has been shown to inhibit the growth of gastric cancer cell lines.…”

Section: Introductionmentioning

confidence: 88%

Anticancer Activity of Calcium Channel Blockers in Colon Cancer Cell Culture

Alandağ

Öztürk

2022

CMJ

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Objective: Repurposing non-cancer drugs for cancer treatment has many advantages. We can access to a new cancer drug easily, quickly and cheaply. In addition, we generally know safety prifile of repurped drugs. There are few studies in the literature investige the anticancer effects of Calcium channel blockers (CCBs). We planned to investigate the anticancer effects of CCBs on colon cancer cell line. Material and Method: We adminestered different doses of T-type CCB NNC-55-0396 and L-type CCB amlodipine on colon cancer cell line HT-29. MTT analysis was performed at 48 hours to measure cell viability. The dose-response curve was constructed using GraphPad Prism.8 programme. Results: Amlodipine caused more than 90% cytotoxicity at all concentrations of 500, 250, 100, 50, 10 µg/ml in MTT analysis at 48 hours. Similarly, NNC-55-0396 caused more than 90% cytotoxicity at all 80, 40, 20, 10.5 µM concentrations. Discussion: In our study, NNC-55-0396 and amlodipine molecules showed severe cytotoxicity on HT-29 cells. There are publications indicating that it may have other anticancer effects other than cytotoxicity. They are promising molecules as anti-cancer drugs. They should be investigated in clinical studies alone or in combination with other cancer drugs.

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Repurposing calcium channel blockers: may be sensible combination with erlotinib for non-small cell lung cancer

Abstract: The Journal is a member of the Committee on Publication Ethics (COPE) which aims to define best practice in the ethics of scientific publishing (www.publicationethics.org).

Cited by 3 publications

References 9 publications

Survival Outcomes of Calcium Channel Blocker Therapy in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Inhibitors: A Retrospective Study

Survival Outcomes of Calcium Channel Blocker Therapy in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Inhibitors: A Retrospective Study

Amlodipine improves the outcomes of regorafenib in metastatic colorectal cancer

Anticancer Activity of Calcium Channel Blockers in Colon Cancer Cell Culture

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