Cancer treatment has long been synonymous with a daunting amalgamation of surgery, chemotherapy, and radiation, often burdened by exorbitant costs and severe side effects. In this milieu, the introduction of repurposed drugs has emerged, casting new light on efficient and affordable alternatives in cancer care. Repurposed drugs are pharmaceuticals initially designed to treat ailments distinct from cancer but have inadvertently shown promise in oncological applications. These drugs possess a remarkable characteristic: they act via multiple biological pathways. Rather than solely targeting cancer cells, they adeptly navigate through a dual route, promoting cell death in cancer cells while simultaneously altering the tumor microenvironment.
This multifaceted approach not only impedes cancer cell proliferation and metastasis but also fortifies the body’s innate immune response against malignancies. Amidst the soaring prices of conventional cancer therapies, repurposed drugs stand out as cost-effective contenders, making them invaluable assets in preventive and therapeutic oncology.
These versatile, economically viable drugs open avenues for accessible treatment options, potentially changing the landscape of cancer care and offering renewed hope to patients worldwide.
Jane McLelland is a pivotal figure in oncology, notably for her influential book, “How to Starve Cancer.” A cancer survivor herself, McLelland offers a unique perspective, melding personal experience with deep research. Her work illuminatively explores the potential of repurposed drugs in cancer treatment, providing patients and practitioners with novel, hopeful strategies.
“How to Starve Cancer” artfully demystifies the concept of leveraging non-cancer drugs, supplements, and dietary changes to inhibit cancer cell growth and survival. McLelland’s insightful approach focuses on manipulating cancer’s metabolic pathways, offering a valuable framework for both prevention and treatment strategies through a deeper understanding of these cellular processes.
Central to McLelland’s contributions is her advocacy for a metabolic approach to cancer care. She introduces the potential of repurposed drugs, such as metformin and statins, to act as powerful tools in starving cancer cells by disrupting their essential fuel supply.
Repurposed Drugs – A Dual Mechanism
The efficacy of repurposed drugs in cancer treatment is underlined by their dual mechanism of action, providing a multifaceted approach to combating the disease. The first mechanism involves direct action on cancer cells, impacting cancer drivers and inhibiting metabolic processes of the cancer cell inducing apoptosis or programmed cell death.
Through influencing various cellular pathways, these drugs disrupt the normal life cycle of cancer cells, preventing their proliferation and ultimately leading to their demise. This direct interference with cancer cell metabolism and growth inhibits tumor development, presenting a proactive strategy for cancer prevention and treatment.
In contrast, the second mechanism alters the tumor microenvironment (TME). The TME, a complex milieu surrounding the tumor, plays a crucial role in cancer progression and metastasis. Repurposed drugs targeting the TME work to restore immune function and enhance T cell cytotoxicity, crucial components in the body’s defense mechanism against cancer.
By limiting angiogenesis—the process through which tumors develop new blood vessels—these drugs effectively starve tumors, restricting their growth and spread. Furthermore, the alteration in the TME also inhibits the formation and function of cancer stem cells, notorious for their role in recurrence and resistance to treatment.
Together, these mechanisms offer a comprehensive approach to cancer prevention and treatment. The direct action on cancer cells limits tumor growth, while modification of the TME creates an environment less conducive to cancer progression. This dual action not only contributes to preventing the onset of cancer but also plays a pivotal role in limiting the spread and recurrence of the disease, making repurposed drugs a promising ally in the fight against cancer.
Spotlight on Repurposed Drugs
Repurposed drugs have taken center stage in the realm of oncology due to their potential therapeutic benefits. Here’s a spotlight on some of these drugs:
Metformin, a staple in diabetes management, has displayed promising results in cancer prevention and treatment by reducing insulin resistance and hyperinsulinemia, which are associated with tumorigenesis. Its ability to inhibit the mTOR pathway and foster AMP-activated protein kinase activation also contributes to its anti-cancer properties.
Mebendazole and Fenbendazole, primarily used for parasitic infections, have revealed anti-cancer potential by disrupting the polymerization of tubulin, thereby inhibiting cancer cell division and metastasis. Preclinical studies suggest their efficacy in glioblastoma and adrenocortical carcinoma, warranting further investigation into their broader oncological applications.
Statins like Simvastatin and Atorvastatin have been studied for their anti-cancer potential, with evidence suggesting they may inhibit tumor growth and metastasis. Their modus operandi involves the inhibition of mevalonate pathway, affecting the synthesis of crucial molecules for cancer cell survival and proliferation.
Doxycycline, an antibiotic, is noted for its ability to inhibit matrix metalloproteinases, enzymes imperative for cancer invasion and metastasis. Research has shown its potential effectiveness in hindering tumor growth and enhancing the effectiveness of conventional cancer therapies.
Low Dose Naltrexone (LDN) has been observed to modulate the immune system and inhibit cell proliferation, showcasing promise in enhancing the body’s natural defenses against cancer.
Ivermectin demonstrates anti-cancer properties by inhibiting the proliferation and metastasis of cancer cells. Laboratory studies have provided insights into its ability to induce cell death in leukemia, ovarian, and breast cancer cells, underscoring its potential therapeutic applications in oncology.
Aspirin has long been studied for its potential role in cancer prevention due to its anti-inflammatory properties. Epidemiological studies suggest a correlation between regular aspirin intake and reduced risk of colorectal, esophageal, and gastric cancers.
Dipyridamole, primarily an anti-thrombotic, has showcased potential anti-cancer properties by inhibiting angiogenesis and tumor growth, although the exact mechanisms remain under investigation.
These drugs, originally developed for different medical conditions, offer a ray of hope in cancer treatment with their unexpected anti-cancer properties. It’s essential to acknowledge that while these repurposed drugs show promise, further rigorous clinical trials are imperative to establish their efficacy, safety profiles, and roles in the integrated paradigm of cancer prevention and treatment. Their potential synergy with existing treatments could pave the way for more effective and affordable cancer therapy strategies in the future.
Overcoming Research Challenges
Research on repurposed drugs faces significant challenges, primarily due to funding constraints often influenced by large pharmaceutical companies’ economic interests. As repurposed drugs are typically off-patent, the profit margin is substantially lower compared to newly developed drugs. This financial dynamic stifles the incentive for big pharmaceutical firms to invest in extensive research and clinical trials for these drugs, even though they may hold promising potential in cancer treatment.
The 2014 ProPublica investigation illuminates this funding dilemma. The investigation uncovered that the pursuit of profit by pharmaceutical giants inadvertently sidelines potential treatments that are affordable. For instance, a Harvard Medical School researcher struggled to secure funding for an aspirin study related to breast cancer, highlighting the funding bias towards patentable, and therefore profitable, drugs.
This phenomenon consequently leaves drugs like aspirin — despite its noteworthy properties — underexplored and underutilized in cancer treatment realms.
In this funding-strapped landscape, studies like METRICS (NCT02201381) are vital. The METRICS study is a participant-funded, open-label, non-randomized, single-arm study aiming to gather valuable data on the safety, tolerability, and effectiveness of a combination of off-label metabolically targeted medicines, including metformin, atorvastatin, mebendazole, and doxycycline, as adjunctive cancer treatments. Initial results from this study have shown encouraging signs, including increased disease-free survival rates among patients, underlining the significant potential of repurposed drugs in cancer treatment.
To unleash the full potential of repurposed drugs, there is an urgent need to navigate and overcome the present funding and research challenges. Addressing these issues will not only foster innovation but also widen access to cost-effective and potentially life-saving cancer treatments for patients globally.
Clinical Evidence and Future Possibilities
The Repurposing Drugs in Oncology (ReDO) project is an exemplary initiative aiming to optimize the use of approved drugs, significantly contributing to the realm of oncology. With a catalog of 268 approved drugs possessing anticancer effects, ReDO provides an extensive resource for researchers and clinicians exploring cost-effective treatment options. It systematically identifies and reviews drugs, prioritizing those with the strongest clinical and mechanistic evidence, thereby facilitating informed selection and application in cancer care.
When examining clinical evidence, it’s crucial to consider the value and limitations of observational studies vis-a-vis randomized controlled trials (RCTs). Observational studies offer valuable insights into the real-world effectiveness of treatments, capturing data from routine clinical practices. They are usually quicker and less expensive to conduct, providing preliminary evidence that can guide further research. However, they are often criticized for potential biases and confounders, making their results less definitive than RCTs. RCTs, the gold standard in clinical research, offer robust evidence due to their rigorous design and control mechanisms but often are expensive and time-consuming.
Implementing a patient-centric approach is pivotal when utilizing repurposed drugs in cancer care. This model prioritizes the unique physiological responses and health profiles of individual patients, crafting personalized treatment plans to optimize therapeutic outcomes. Personalized plans consider the patient’s overall health, type and stage of cancer, and response to previous treatments, providing a tailored strategy that enhances the efficacy of repurposed drugs while minimizing potential side effects.
Continuous monitoring is equally crucial, as it allows healthcare providers to track the patient’s progress and adjust treatment protocols dynamically. Monitoring involves regular assessments through tools like PET scans, tumor markers, and emerging technologies that evaluate circulating tumor DNA. These instruments offer invaluable insights into the patient’s response to the treatment, facilitating timely modifications to the treatment plan if necessary.
For patients considering repurposed drugs, it’s imperative to engage in open dialogues with healthcare providers, discussing the potential risks and benefits of these drugs in the context of their overall treatment strategy. Healthcare providers should stay abreast of the latest research and clinical trials regarding repurposed drugs, incorporating this knowledge into their practice to offer informed recommendations to patients.
Engaging in shared decision-making, patients and providers can collaboratively explore the potential of repurposed drugs as adjunctive or alternative treatments, navigating the path to recovery with evidence-based, patient-centered care.
Repurposed drugs usher in a hopeful chapter in cancer care, presenting a feasible, affordable treatment alternative for patients and a transformative opportunity for the medical community. These accessible therapies not only bring hope to those grappling with cancer but also showcase the potential of innovative, patient-centric medical practices.
With the introduction of repurposed drugs, a cancer diagnosis need not be entangled with fear and financial strain. These drugs, by offering effective and affordable options, illuminate a path of optimism and possibilities. For the medical fraternity, this development is a call to embrace and integrate these promising alternatives into personalized treatment regimens, ensuring a wider reach and accessibility to life-saving therapies for patients globally.
As we navigate through the complexities of oncology, repurposed drugs stand out as a potential, heralding a future where cancer treatment is not only effective but also financially accessible and patient-focused. The journey, though challenging, is promising, with repurposed drugs lighting the way towards a more hopeful and inclusive future in cancer care.
For those ready to explore the possibilities that repurposed drugs offer in cancer treatment, The Karlfeldt Center, a national leader in integrative oncology, is here to guide your journey.
To embark on a path of informed, innovative, and personalized cancer care, schedule a free 15-minute discovery call with Dr. Karlfeldt by calling 208-338-8902 today.
Discover hope, embrace possibilities, and take active steps towards a future where cancer treatment is effective, accessible, and tailored just for you.
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- Coyle, C., Cafferty, F.H., Vale, C., & Langley, R.E. (2016). Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Annals of Oncology, 27(12), 2184-2195. doi: 10.1093/annonc/mdw410. The systematic review and meta-analysis study provides critical insight into the role of metformin as an adjuvant treatment for cancer.
- Guerini, A.E., Triggiani, L., Maddalo, M., Bonù, M.L., Frassine, F., Baiguini, A., Alghisi, A., Tomasini, D., Borghetti, P., Pasinetti, N., Bresciani, R., Magrini, S.M., & Buglione, M. (2019). Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature. Cancers (Basel), 11(9), 1284. doi: 10.3390/cancers11091284. This extensive review of current literature presents mebendazole as a candidate for drug repurposing in oncology.
- Huang, S., Zhang, N-Q., Xu, C-J., Huang, W-Q., Li, D-X., Li, J., Yao, L-L., Sundquist, K., Sundquist, J., Jiang, S-H., Xing, X., Hu, L-P., Zhang, Z-G., Ji, J., & Zhang, X-L. (2023). Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner. Cell Oncology (Dordr), 46(4), 953-967. doi: 10.1007/s13402-023-00789-7. This article demonstrates how dipyridamole can enhance the anti-cancer abilities of aspirin, specifically against colorectal cancer, through inducing apoptosis in a UPR-dependent manner.
- Jiang, W., Hu, J-W., He, X-R., Jin, W-L., & He, X-Y. (2021). Statins: a repurposed drug to fight cancer. Journal of Experimental & Clinical Cancer Research, 40(1), 241. doi: 10.1186/s13046-021-02041-2. This research explores the repurposing of statins as a viable strategy in cancer treatment, providing significant insights into their potential role and mechanism of action against various cancer types.
- Pantziarka, Pan et al. “The Repurposing Drugs in Oncology (ReDO) Project.” ecancermedicalscience, 2014. This paper provides insights into the ReDO project, its objectives, and initial findings regarding repurposed drugs in oncology.