Repurposing Drugs: A Cost-Effective Strategy for Cancer Treatment

Introduction to Drug Repurposing in Oncology

What is Drug Repurposing?

Drug repurposing involves finding new medical uses for existing FDA-approved drugs originally developed for other diseases. In oncology, this means using well-known medications to treat cancer, offering an alternative to traditional drug development.

Advantages Compared to Traditional Drug Development

Unlike creating new drugs from scratch—which typically takes over a decade and billions of dollars—repurposed drugs have established safety profiles and known pharmacokinetics. This allows for faster clinical implementation, often bypassing initial safety trials and reducing development costs dramatically. For example, drug approval timelines can shrink from 13–15 years down to around 6.5 years, with costs falling from billions to hundreds of millions.

Why is This Important for Cancer Treatment?

Cancer remains a leading cause of death worldwide, with growing global incidence driving demand for effective and affordable therapies. Traditional cancer drug development has challenges such as high costs, lengthy timelines, and significant side effects. Drug repurposing leverages well-tolerated drugs, some used chronically, to improve cancer treatment innovation rapidly and cost-effectively. This strategy addresses unmet medical needs, especially for cancers with limited options, and opens possibilities for combination treatments and personalized medicine approaches.

What Is Drug Repurposing and Why Does It Matter?

Definition and basic concept of drug repurposing

Drug repurposing involves identifying new therapeutic uses for existing, approved medications beyond their original indications. Instead of developing entirely new drugs, researchers find novel applications for known drugs, leveraging their established safety profiles and pharmacokinetics. This approach can significantly shorten development timelines and reduce risks compared to traditional drug discovery.

Reduction in cost and time compared to new drug development

Traditional cancer drug development often takes 10 to 15 years and can cost billions of dollars. In contrast, repurposing can reduce development costs from around $2–3 billion to approximately $0.3 billion and cut timelines roughly in half, sometimes to just 6-7 years. Many repurposed drugs bypass early-phase trials due to existing clinical data on safety, offering a faster route to patient access and lower overall expense (Drug repurposing benefits).

Examples of approved drugs repurposed for cancer

Several approved drugs have successfully been repurposed for cancer treatment. Notable examples include:

• Arsenic trioxide and all-trans retinoic acid: for acute promyelocytic leukemia, revolutionizing treatment (Drug repurposing in cancer therapy).
• Thalidomide: originally a sedative, repurposed for multiple myeloma (Drug repurposing in cancer therapy.
• Metformin: first-line anti-diabetic drug, shown to reduce risk and mortality in various cancers including breast, colorectal, and pancreatic cancers (Anti-diabetic drugs for cancer treatment).
• Propranolol: a beta-blocker used for hypertension, displaying anti-cancer effects in studies on breast and colorectal cancers (Anti-hypertensive drugs with anti-cancer effects.

Other promising candidates include natural compounds like salidroside and triptolide, and drugs such as disulfiram, which work by inhibiting cancer cell proliferation or inducing programmed cell death (Drug repurposing in cancer therapy.

Researchers are also investigating advanced delivery technologies such as nanoparticle carriers for repurposed drug delivery to target tumors more precisely and reduce side effects. Institutions like the Winship Cancer Institute are actively conducting clinical trials to validate repurposed therapies, highlighting their potential to provide cost-effective, safer cancer treatment options.

Covered question summary

What are some examples of drug repurposing in cancer treatment? Examples include arsenic trioxide and all-trans retinoic acid for acute promyelocytic leukemia, thalidomide for multiple myeloma, and drugs like metformin and propranolol repurposed for solid tumors. Innovative drugs such as salidroside and disulfiram illustrate the expanding horizon, as does the use of nanotechnology to enhance effectiveness and reduce toxicity, accelerating the availability of novel, affordable cancer therapies.

Repurposing Anti-Diabetic and Anti-Hypertensive Drugs: A Dual Benefit

How do anti-diabetic drugs like metformin contribute to cancer prevention and treatment?

Anti-diabetic drugs, especially metformin, have been widely studied for their role beyond glucose control. Metformin's role in reducing cancer risk is linked with a lower risk and mortality in cancers such as colorectal, breast, pancreatic, prostate, lung, and cervical cancers. This benefit likely stems from metformin’s impact on cancer cell metabolism—including reducing glucose uptake—and indirect effects like lowering hyperglycemia, inflammation, and obesity. Epidemiological studies show that patients with diabetes have higher risks for several cancer types, making metformin a prime candidate for prevention and therapy due to its safety and efficacy at low doses for long periods (Mechanisms of anti-diabetic agents in cancer.

What effects do anti-hypertensive drugs have on tumor growth and metastasis?

Anti-hypertensive medications like propranolol and ACE inhibitors (e.g., captopril) demonstrate anti-cancer properties. They can inhibit tumor angiogenesis, decrease cell proliferation, induce apoptosis, and modify the tumor microenvironment (TME) modulation by repurposed drugs. For example, propranolol promotes apoptosis in neuroblastoma by activating p53-dependent pathways and reactive oxygen species (ROS). Moreover, these drugs may improve chemotherapy response and reduce metastasis. Their influence on hypoxia-inducible factors and immune modulation supports tumor suppression across various cancer types, including colorectal, breast, prostate, pancreatic, and lung cancers (Anti-hypertensive drugs inducing tumor cell apoptosis; Inhibition of tumor angiogenesis by anti-hypertensives.

What clinical evidence supports the use of these drug classes in cancer therapy?

There is robust clinical trial activity evaluating both anti-diabetic and anti-hypertensive drugs in oncology. Over 92 clinical trials involve anti-diabetics, with metformin cancer clinical trials in advanced Phase III studies for several cancers. Similarly, around 40 trials focus on anti-hypertensives, with propranolol and captopril reaching Phase IV approval for certain benign tumors. Trials confirm these drugs’ safety, tolerability, and potential to improve survival outcomes. The breadth of cancers targeted and trial phases suggest promising translational potential for repurposing chronic medications as adjuncts or primary cancer therapies (Clinical trials of anti-diabetic drugs in cancer; Clinical trials of anti-hypertensive drugs in cancer; Advanced trial stages of metformin and propranolol.

Drug Class	Examples	Anti-Cancer Mechanisms
Anti-Diabetics	Metformin, SGLT2 inhibitors	Modulate metabolism, reduce inflammation and obesity-related risks
Anti-Hypertensives	Propranolol, Captopril	Induce apoptosis, inhibit angiogenesis, modulate TME
Clinical Status	Varied (Phases II-IV)	Extensive trials demonstrating efficacy and safety

This dual benefit approach exploits well-tolerated, chronic-use drugs to enhance cancer care with potentially lower costs and manageable side effects (Drug repurposing in cancer therapy.

Mechanisms Underpinning Repurposed Drug Actions in Cancer

How do repurposed drugs target cancer cell metabolism and the tumor microenvironment?

Repurposed drugs often exploit vulnerabilities in cancer cell metabolism to hinder tumor growth. Anti-diabetic drugs like Metformin's role in reducing cancer risk reduce glucose uptake and affect cellular metabolism, which starves cancer cells of energy and inhibits their proliferation. Additionally, these drugs can modulate systemic risk factors such as hyperglycemia, hyperinsulinemia, and obesity that contribute indirectly to tumor progression. Furthermore, repurposed drugs influence the tumor microenvironment (TME) modulation by repurposed drugs by targeting components like hypoxia, inflammation, and angiogenesis, altering conditions that support cancer survival and spread. For more on these mechanisms, see Mechanisms of anti-diabetic agents in cancer and Tumor microenvironment targeting by repurposed drugs.

What signaling pathways are modulated by repurposed drugs to induce cancer cell death and impede tumor progression?

Repurposed agents regulate multiple oncogenic signaling pathways involved in apoptosis, angiogenesis, and immune responses. For instance, anti-hypertensive drugs like Propranolol and captopril in cancer treatment induce apoptosis in tumor cells through pathways involving p53 activation and reactive oxygen species (ROS) generation. These drugs also inhibit angiogenesis, the formation of new blood vessels, which tumors need for growth and metastasis. Moreover, they can enhance chemotherapy efficacy and modulate immune system components to improve anti-tumor immunity. Additional insights can be found in Anti-hypertensive drugs inducing tumor cell apoptosis and Immunomodulatory effects of propranolol.

What are notable examples of repurposed drugs and their mechanisms in cancer therapy?

• Propranolol: A beta-blocker that promotes apoptosis in neuroblastoma and other tumors via p53 activation and ROS production; also impairs angiogenesis and tumor cell proliferation. See detailed mechanisms and clinical trials.
• Metformin: Primarily an anti-diabetic drug, it lowers cancer risk by affecting cancer cell metabolism, reducing glucose availability, and modulating pathways that regulate tumor growth and survival. Clinical trials and molecular effects.
• Pioglitazone: An anti-diabetic medication that induces cell cycle arrest, apoptosis, and ferroptosis while inhibiting angiogenesis in various cancer models. Anti-diabetic drugs in cancer therapy.

Together, these mechanisms underscore how repurposed drugs act on cancer's metabolic and signaling hallmarks, offering promising adjuncts or alternatives to conventional treatments. For comprehensive reviews on these drug repurposing approaches and their clinical applications, see Drug repurposing in cancer therapy and Drug repurposing in oncology.

Clinical Trials and Development Status of Repurposed Drugs

Current phases and scale of trials for repurposed drugs

Drug repurposing in oncology is experiencing active clinical research with numerous ongoing trials. Over 92 clinical trials are evaluating anti-diabetic drugs, and about 40 trials are focused on anti-hypertensive drugs, targeting more than 15 cancer types. Many of these trials are in Phase II and III stages, reflecting significant interest and clinical progress in validating these drugs’ anticancer potential. This extensive trial activity highlights the commitment to integrating repurposed drugs into cancer treatment.

Notable examples in advanced trial stages such as metformin and propranolol

Metformin, a widely used anti-diabetic drug, stands out with over 350 clinical trials involving cancer patients. It has advanced to Phase III trials for different cancer types, including colorectal, breast, pancreatic, and lung cancers, likely due to its effects on cancer metabolism and inflammation reduction. Similarly, propranolol, a beta-blocker used for hypertension, demonstrates promising anticancer activity. It is in Phase III and IV trials and has even received approval for specific benign tumors. Propranolol has shown efficacy in inducing tumor cell apoptosis and inhibiting angiogenesis, making it a promising candidate in cancer therapy.

Challenges in drug licensing and clinical adoption

Despite encouraging clinical data, repurposed drugs face challenges such as complex drug licensing procedures and difficulties in widespread clinical adoption. Patent limitations, regulatory hurdles, and lack of commercial interest due to off-patent status contribute to funding and development obstacles. Additionally, coordinated efforts are needed to standardize clinical trial designs and ensure regulatory clearance. Overcoming these barriers is critical for the successful translation of repurposed drugs from trials to routine cancer care.

Cost-Effectiveness of Drug Repurposing in Oncology

What does cost-effectiveness mean in oncology and why is it important?

Cost-effectiveness analysis (CEA) in oncology assesses the balance between the costs of cancer treatments and the health outcomes they achieve, such as survival or quality-adjusted life years (QALYs). This evaluation helps healthcare providers and policymakers determine which therapies offer the best value, ensuring sustainable cancer care that maximizes patient benefit while controlling expenses. For further reading on Cost-Effectiveness Analysis in Oncology and delivering affordable cancer care, see these resources.

How does drug repurposing compare in cost to traditional cancer drug development?

Traditional new cancer drug development is highly costly and prolonged, often requiring 10 to 15 years and about $1 to $3 billion due to extensive clinical trials and regulatory hurdles. In contrast, Drug repurposing in cancer therapy leverages existing FDA-approved medicines with known safety profiles, reducing development costs to roughly $0.3 billion and timelines to about 6.5 years. Many repurposed drugs can bypass early-phase trials, further accelerating clinical adoption and lowering costs. See also Drug repurposing benefits and challenges and Drug repurposing in oncology for detailed insights.

What do cost-utility analyses reveal about affordability of repurposed cancer drugs?

Systematic reviews show that many cancer interventions are cost-effective, with median incremental cost-effectiveness ratios (ICERs) between $24,000 and $29,000 per QALY, well below the commonly accepted $50,000 threshold. Repurposed drugs, often generic and low-toxicity, align with this affordability, presenting promising options especially in resource-constrained healthcare systems. By repurposing drugs like metformin and propranolol, ongoing Phase II-IV trials indicate clinical and economic progress. Additional information on Cancer Prevention Cost-Effectiveness and the Cost-effectiveness of cancer treatment can provide further context.

What is the potential impact of drug repurposing on healthcare systems and patient access?

Repurposing drugs can alleviate financial burdens on health systems by offering effective, lower-cost alternatives to novel targeted therapies. This approach can enhance patient access to cancer treatments globally, including in low- and middle-income countries where high pharmaceutical costs limit care. Ultimately, repurposing supports sustainable cancer control by shortening development cycles, reducing side effects, and facilitating personalized medicine strategies without sacrificing quality or efficacy. For comprehensive perspectives, see Drug repurposing in cancer care and combating cancer cost-effectively.

Overcoming Economic Barriers: Supporting Patients with Limited Resources

How can patients afford cancer treatment if financial resources are limited?

Accessing cancer treatment can be financially challenging, but multiple support mechanisms exist to aid patients with limited resources.

Financial assistance programs including Medicare and Medicaid

Federal programs play a crucial role in reducing the financial burden of cancer care:

• Medicare: Provides coverage through various parts—hospital stays (Part A), outpatient services (Part B), and prescription drugs (Part D). It mainly supports individuals over 65 or with certain disabilities.
• Medicaid: Designed for individuals with low income, this program offers extensive coverage for cancer treatment costs. Eligibility and benefits differ by state but are integral for patients with limited means.
• Veterans Administration: Provides healthcare services, including cancer treatment, to eligible veterans.
• Medicare Prescription Payment Plan (M3P): Helps patients by spreading out medication costs over time, improving affordability.

Role of nonprofit organizations and patient support initiatives

Numerous nonprofit groups and hospital programs provide financial support and resources to cancer patients, including:

• Covering medication expenses or treatment-related costs
• Offering transportation assistance and supportive care services
• Facilitating access to counseling and education about managing treatment costs

These grassroots initiatives bridge gaps where government programs may fall short.

Strategies to reduce treatment costs with repurposed drugs

Drug repurposing in cancer therapy leverages well-established medications with known safety profiles originally developed for other conditions, such as anti-diabetic drugs and anti-hypertensive drugs with anti-cancer effects.

Benefits include:

• Lower development cost and time: Repurposed drugs often bypass early clinical trials and have existing efficacy and safety data.
• Reduced treatment costs: Often available as generics, repurposed drugs provide affordable options compared to novel cancer therapies.
• Improved tolerability: Suitable for long-term use at low doses, supporting sustained treatment with fewer side effects.

Together, financial assistance programs, nonprofit support, and innovations like drug repurposing in cancer therapy form a comprehensive framework to help patients overcome economic barriers to cancer care.

Integration of Drug Repurposing and Immunotherapy: New Horizons

What is immunotherapy and why is it considered an advanced therapy for cancer?

Immunotherapy represents a breakthrough in cancer treatment by empowering the body's immune system to identify and eliminate cancer cells more efficiently. Unlike conventional therapies that directly attack tumors, immunotherapy employs strategies such as checkpoint inhibitors, monoclonal antibodies, adoptive cell transfers, and cancer vaccines. These approaches stimulate or restore the immune system's natural capacity to combat malignancies, often resulting in improved long-term survival with lower toxicity. For more on advances in cancer treatment including immunotherapy, see Cancer Treatment Advances at MSK 2024.

How can repurposed drugs enhance immunotherapy responses?

Repurposed drugs, originally approved for non-cancer uses, have shown promising potential to amplify immunotherapy effectiveness. Certain medications—including beta blockers, NSAIDs, histamine blockers, fenofibrates, and probiotics—can modulate immune responses or remodel the tumor microenvironment (TME) modulation by repurposed drugs to favor immune activation. For example, beta blockers like propranolol may increase immune sensitivity of tumors, while anti-inflammatory agents reduce immunosuppressive factors, thereby improving the efficacy of immune checkpoint inhibitors and adoptive cell therapies. For details about repurposing FDA-approved drugs for cancer and their immunotherapy benefits, see Drug repurposing in cancer care and Drug repurposing in cancer therapy.

Emerging combination therapies and clinical trial insights

Integrating repurposed drugs with immunotherapies is an active area of clinical research. Many ongoing trials are evaluating combinations that enhance immune activation or reduce resistance mechanisms. For instance, trials are assessing histamine 1 blockers combined with checkpoint inhibitors to heighten immune surveillance. This synergistic approach aims to expand the spectrum of responsive cancers and to augment durable treatment outcomes. The clinical evidence so far points to improved response rates and survival benefits, paving the way for novel multimodal regimens that leverage the safety profiles and cost-effectiveness of repurposed agents alongside cutting-edge immunotherapy techniques. For clinical trials and combination therapy insights, see Clinical Trials on Repurposed Cancer Drugs and Drug repurposing in cancer therapy.

Innovative Delivery Systems Enhancing Repurposed Drug Efficacy

Nanotechnology-based drug delivery platforms

Nanotechnology has emerged as a groundbreaking approach to enhance the effectiveness of repurposed drugs in cancer therapy. Utilizing delivery systems such as liposomes, polymeric nanoparticles, micelles, and hydrogels, these platforms improve targeted drug delivery directly to tumor sites.

Advantages like improved targeting, reduced toxicity, and overcoming drug resistance

These advanced delivery systems offer several advantages. They enhance drug targeting to cancer cells, minimizing exposure to healthy tissues and thereby reducing toxicity. Additionally, nanocarriers can overcome drug resistance by facilitating the sustained release of therapeutic agents and enabling the delivery of drugs at effective concentrations within tumors. This results in improved therapeutic outcomes and fewer side effects for patients.

Examples including liposomes, nanoparticles, and hydrogels in ongoing trials

Several nanotechnology-based delivery methods are actively tested in clinical trials involving repurposed drugs. For instance, liposomes loaded with niclosamide and PLGA (poly(lactic-co-glycolic acid)) nanoparticles enhance drug stability and accumulation in tumor tissues. Silk fibroin nanoparticles and gold nanoparticle carriers loaded with phytochemicals are also explored for their capacity to augment anticancer effects. Hydrogels provide controlled and localized drug release, further improving treatment precision. These innovations represent a promising frontier in making repurposed drug therapies more effective and safer in cancer care.

Future Outlook: Emerging Therapies and Expanding Clinical Applications

What are the most promising new cancer treatments expected in 2025?

By 2025, cancer treatment is poised to advance with several groundbreaking therapies. Immunotherapy has made remarkable strides, notably achieving nearly 80% success rates in treating mismatch repair-deficient tumors without the need for surgery or radiation. This breakthrough promises greatly improved quality of life for patients. Targeted therapies are making headway as well, with agents like Ulixertinib showing effectiveness in rare blood cancers, and zoldonrasib demonstrating significant tumor shrinkage in lung cancers harboring KRAS-G12D mutations. Such therapies highlight the growing impact of personalized medicine. (Cancer Treatment Advances at MSK 2024)

Innovative delivery methods are also improving outcomes for challenging cancers. For example, convection-enhanced delivery (CED) has shown promise in treating pediatric brain tumors such as diffuse intrinsic pontine glioma (DIPG), with some cases achieving survival beyond three years post-treatment. Meanwhile, combination drug regimens, including agents like inavolisib paired with standard therapies, are extending survival for hormone receptor-positive breast cancer patients. CAR T cell therapies continue to expand their reach, effectively treating diseases like AL amyloidosis. (Drug repurposing for cancer treatment)

Can repurposed drugs complement these new cancer therapies?

Repurposed drugs stand to play a crucial complementary role alongside these advances. Many repurposed agents, such as metformin and propranolol, are under active clinical investigation and could enhance the efficacy of novel treatments by targeting cancer metabolism, tumor microenvironment (TME) modulation by repurposed drugs, or resistance pathways. The known safety profiles and affordability of these chronically used drugs make them valuable adjuncts, particularly in personalized treatment plans where multiple mechanisms must be addressed. Their integration with emerging therapies could also improve outcomes while helping manage treatment costs. (Drug Repurposing in Cancer Care, Drug repurposing in oncology

How will personalized medicine and therapy sequencing improve cancer outcomes?

Personalized medicine is central to these advances, with molecular profiling guiding the selection of targeted treatments optimized for individual tumor characteristics. For example, therapies targeting specific genetic mutations like KRAS G12D enable tailored approaches that maximize tumor response. Additionally, research highlights the importance of treatment sequencing; initiating therapy with targeted agents before immunotherapy results in better survival and cost-effectiveness for some cancers. This strategic sequencing, combined with biomarker-driven personalization, offers a more effective and efficient cancer care paradigm moving forward. (Cancer treatment sequences)

Repurposing Drugs as a Means to Reduce or Replace Surgery

What recent breakthroughs have been made in cancer treatment that could replace surgery?

Recent advances have revealed that immunotherapy can significantly alter cancer treatment, potentially replacing the need for surgery in some cases. Notably, pembrolizumab (Keytruda), an immune checkpoint inhibitor, has shown groundbreaking results in clinical trials involving patients with high-risk colorectal cancer who possess mismatch repair deficiency (MMR) or microsatellite instability-high (MSI-High) genetic profiles.

Breakthroughs in immunotherapy reducing surgical need

In a recent clinical trial, administering pembrolizumab prior to any surgical intervention yielded impressive outcomes—59% of treated patients were cancer-free post-therapy. This contrasts sharply with the less than 5% cancer-free rate observed in patients who received conventional chemotherapy before surgery. Such data suggest pembrolizumab not only effectively shrinks tumors but might also eliminate the tumor entirely, raising the possibility that surgery could be avoided in a significant fraction of patients.

Clinical trial results such as pembrolizumab in colorectal cancer

The pivotal study's findings underscore the potential of immunotherapy as a primary treatment modality. By activating the patient's immune system to target and destroy cancer cells more efficiently, pembrolizumab enhances survival chances and reduces treatment-related side effects that often accompany surgery and chemotherapy.

Implications for patient outcomes and healthcare system savings

Avoiding surgery can profoundly benefit patients, reducing risks associated with invasive procedures and improving quality of life. For healthcare systems, fewer surgeries translate into cost savings and resource optimization. However, comprehensive research and long-term follow-up are essential to validate these promising results and extend this treatment approach to other cancer types.

Conclusion: The Promise and Path Forward for Drug Repurposing in Cancer Care

Cost-Effectiveness and Clinical Potential of Repurposed Drugs

Drug repurposing offers a compelling approach to cancer care by significantly reducing development costs and timelines compared with traditional drug discovery. The known safety profiles of many chronic-use medications, such as anti-diabetics and anti-hypertensives, enable faster clinical translation. Furthermore, numerous clinical trials—spanning Phase II to Phase IV—underscore the therapeutic potential of repurposed agents like metformin and propranolol across a wide range of cancers.

Continued Research and Policy Support

While early clinical successes are encouraging, rigorous research must continue to confirm efficacy and optimize treatment regimens. Overcoming challenges such as regulatory hurdles, patent limitations, and funding scarcity will require dedicated policy frameworks and advocacy efforts. Enhanced clinical trial designs, including biomarker-driven studies and community-based registries, will help validate repurposed drugs’ impact and promote equitable patient access.

Integrating Repurposed Drugs into Cancer Treatment

Looking forward, repurposed medications hold promise when integrated into multimodal treatment strategies. They can complement existing therapies by targeting tumor metabolism, microenvironment, and immune response pathways. Advances in nanotechnology and personalized medicine will further enhance their precision and effectiveness. Ultimately, repurposing represents a sustainable, cost-effective avenue to expand the arsenal against cancer, improving patient outcomes and health equity on a global scale.