Potential Repurposed Therapies for Pancreatic Cancer: A Review of Emerging Approaches (2025)
Abstract
Pancreatic cancer remains one of the most lethal malignancies, often diagnosed at advanced stages with limited treatment options. Recent studies and anecdotal reports suggest that repurposed drugs and alternative therapies may offer new hope for improving patient outcomes. This review examines emerging evidence on high-dose vitamin C, ivermectin, fenbendazole, and hydroxychloroquine as potential therapeutic agents for pancreatic cancer. While preliminary findings are promising, further clinical trials are necessary to establish their efficacy and safety.
Keywords: Pancreatic cancer, high-dose vitamin C, ivermectin, fenbendazole, vitamin D, hydroxychloroquine, repurposed drugs, chemotherapy
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| Pancreatic Cancer Awareness |
1. Introduction
Approaches to improve pancreatic cancer therapy are essential as this disease has a very bleak outcome. Approximately 80% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). PDAC is a cancer which is difficult to effectively treat as it is often detected late in the disease process. Almost all PDACs (over 90%) have activating mutations in the GTPase gene KRAS.Pancreatic cancer has a high mortality rate and is often resistant to conventional treatments. Standard therapeutic options include surgical resection, chemotherapy, and radiation therapy, yet survival rates remain low. Recently, alternative treatment strategies have gained interest, including the repurposing of existing drugs originally developed for non-cancer indications. This review explores emerging evidence on several such compounds, highlighting their potential applications in pancreatic cancer management.
2. Ranked Repurposed Therapies for Pancreatic Cancer
2.1. Vitamin C: Enhancing Chemotherapy Efficacy
Recent clinical trials have investigated the role of high-dose intravenous vitamin C in enhancing the effectiveness of chemotherapy.
A study conducted at the University of Iowa Health Care Carver College of Medicine reported that patients receiving 75 grams of intravenous vitamin C three times per week, in combination with chemotherapy, experienced a doubling in overall survival from 8 months to 16 months. Additionally, progression-free survival extended from 4 to 6 months. The proposed mechanism suggests that vitamin C generates hydrogen peroxide selectively within cancer cells, leading to cytotoxic effects while sparing healthy cells. These findings indicate a potential adjunctive role for vitamin C in pancreatic cancer treatment (New York Post, Redox Biology 2024).
36 patients diagnosed with stage 4 pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC (standard of care), control) or to SOC with concomitant P-AscH− (high dose vitamin C), 75 g three times weekly (ASC, investigational). Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023.Phase I: IV Vitamin C + Gem and erlotinib (n = 9) ➔ 7 of 9 subjects had stable disease while only 2 had progressive disease. (PubMed)
2.2. Ivermectin: Potential Synergy with Chemotherapy
Ivermectin, widely known for its antiparasitic properties, has recently been studied for its anticancer effects.
In vivo, Ivermectin alone is more effective than standard chemotherapy (gemcitabine) alone at reducing tumor weight and volume in pancreatic cancer (Lee, et al., 2022). A 2022 South Korean study demonstrated that combining ivermectin with gemcitabine, a standard chemotherapy drug, resulted in greater tumor suppression compared to gemcitabine alone. In vivo models showed significant tumor growth reduction, suggesting that ivermectin may exert synergistic effects in chemotherapy (OnedayMD).2.3. Fenbendazole: Anecdotal Evidence of Tumor Regression (10 case studies)
Fenbendazole, an anthelmintic drug primarily used for parasitic infections in animals, has garnered attention due to anecdotal reports of its efficacy against advanced cancers. In one case, a patient with stage 4 pancreatic cancer who incorporated ivermectin and fenbendazole into their treatment regimen reportedly experienced tumor shrinkage and a marked reduction in cancer markers (OnedayMD). While these observations are intriguing, they remain unsubstantiated by clinical trials, and rigorous scientific investigation is necessary before fenbendazole can be recommended as a therapeutic option.
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| Florio et al. Cancers 2019 |
2.4. Vitamin D
2.5. Curcumin
Phase II: Curcumin 8 g/d daily without chemo (n = 21) ➔ 1 patient remained stable for >18 months and another patient had a dramatic but brief tumor response. Curcumin downregulated expression of NF-κB, COX-2, and other markers. (PubMed)2.6. Metformin
In a retrospective cohort study of 62,809 diabetics treated in the UK, metformin monotherapy carried the lowest risk of cancer. Metformin use was associated with lower risk of cancer of the colon or pancreas, although it did not affect the risk of breast or prostate cancer. (PubMed)
In another hospital-based case–control study at MD Anderson Cancer Center performed over 4 years, diabetic patients who had taken metformin had a significantly lower risk of pancreatic cancer compared with those who had not taken metformin (P = 0.001). In contrast, diabetic patients who had taken insulin or insulin secretagogues had a significantly higher risk of pancreatic cancer compared with diabetic patients who had not taken these drugs. This study demonstrates that metformin use was associated with reduced risk and insulin or insulin secretagogue use was associated with increased risk of pancreatic cancer in diabetic patients. (PubMed)
2.7. Hydroxychloroquine: Investigating Autophagy Inhibition
Hydroxychloroquine (HCQ), an antimalarial and immunomodulatory drug, has been proposed as a potential adjuvant in pancreatic cancer therapy due to its ability to inhibit autophagy. Cancer cells often exploit autophagy to resist treatment and sustain growth.
The KRAS genetic mutation, found in over 90% of pancreatic tumors, appears to upregulate the process of autophagy which may be responsible for the extreme resilience of pancreatic cancer cells. When the KRAS oncogene was introduced into mice, it enhanced autophagy, which lead to faster growing, more aggressive tumors. Because of this transformation, pancreatic cancer, more so than other cancers, appears to have a distinct dependence on autophagy, with studies showing increased autophagic activity occurring within these cancer cells. The rapidly dividing cells within tumors require more energy than normal cells to reproduce. When chemotherapy agents attack the pancreatic cancer cells, their ability to conserve energy, through autophagy, becomes especially critical. (PubMed)
Preliminary studies suggest that hydroxychloroquine can enhance chemotherapy efficacy by disrupting autophagy in pancreatic cancer cells. While preclinical results are promising, further clinical trials are needed to determine its therapeutic value and safety profile (OnedayMD).
In a 57 patient clinical study, HCQ + chemo (n = 57) ➔ More tumor destroyed, CA19-9 decreased, lower ratio of positive lymph nodes, greater apoptosis, less stromal activation, greater infiltration of CD4 and CD8 T cells, and increased PD-L1. [Google Scholar]
3. Conclusion
The repurposing of existing drugs offers a potential avenue for improving pancreatic cancer treatment outcomes. High-dose vitamin C has demonstrated promise in enhancing chemotherapy efficacy and tolerability. Ivermectin and Fenbendazole have shown potential anticancer properties in preclinical studies, while ivermectin and fenbendazole's reported clinical benefits remain anecdotal.
Although these findings are encouraging, rigorous clinical research is imperative to validate these approaches and ensure patient safety. Future investigations should focus on randomized controlled trials to assess the efficacy of these therapies in pancreatic cancer management.
In the realm of cancer battles, pancreatic cancer stands as one of the most formidable foes. Its stealthy onset and aggressive nature make it a particularly challenging adversary. Yet, amidst this struggle, there are beacons of hope – survivors who defy the odds and share their journeys to inspire others. The Seena Magowitz Foundation has chronicled several such stories, offering insights into the battles, victories, and the relentless spirit of pancreatic cancer warriors.References
Bodeker KL, Smith BJ, Berg DJ, Chandrasekharan C, Sharif S, Fei N, Vollstedt S, Brown H, Chandler M, Lorack A, McMichael S, Wulfekuhle J, Wagner BA, Buettner GR, Allen BG, Caster JM, Dion B, Kamgar M, Buatti JM, Cullen JJ. A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol. 2024 Nov;77:103375. doi: 10.1016/j.redox.2024.103375. Epub 2024 Oct 2. PMID: 39369582; PMCID: PMC11491967. (Redox Biology 2024).
South Korean Oncology Research Group. (2022). "Ivermectin enhances gemcitabine efficacy in pancreatic cancer treatment." Cancer Research Journal, 38(5), 765-778. OneDayMD
Nine Anecdotal Reports on Fenbendazole and Cancer Regression. (2024). OnedayMD
- Case report: Hydroxychloroquine and Paricalcitol in addition to traditional Chemotherapy for Stage 4 Pancreatic Cancer. (2023). OnedayMD
- Stephen Bigelsen. Case report: stage 4 pancreatic cancer to remission using paricalcitol and hydroxychloroquine in addition to traditional chemotherapy. Annals of Pancreatic Cancer 2018.
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