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Introduction to Drug Repurposing in Oncology
Understanding Drug Repurposing in Cancer
Drug repurposing refers to the strategy of identifying new therapeutic uses for existing drugs that have already been approved by regulatory agencies such as the FDA. These drugs, originally developed for other conditions, are investigated for their potential benefits in cancer treatment.
Benefits Over Traditional Drug Development
This approach offers multiple advantages: significantly reducing both the cost and timeline typically required for cancer drug development. Because safety profiles and pharmacokinetics of these drugs are already established, researchers can bypass many early-phase clinical studies. This accelerates the translation of discoveries into clinical practice, offering patients faster access to potential therapies.
Growth of Research in Drug Repurposing
Research in drug repurposing for oncology has grown steadily, with a compound annual growth rate of about 37.5% from 2008 to 2024. The United States and China lead the field in research output and citation impact. This expanding interest highlights the value seen in repurposed drugs as innovative cancer therapies, promising to revolutionize treatment approaches with a more cost-effective and efficient model.
Accelerating Cancer Therapy Development through Drug Repurposing
What makes drug repurposing a promising approach in oncology?
Drug repurposing is gaining traction as a highly promising approach in cancer therapy because it leverages existing FDA-approved drugs for cancer therapy or investigational drugs for new cancer indications. This strategy significantly reduces both the development time and costs compared to traditional drug discovery, which typically takes over a decade and billions of dollars to bring a new agent to market. By building on previously established safety data and pharmacokinetic profiles, repurposed drugs carry less risk during early clinical development.
How are FDA-approved drugs leveraged for new cancer indications?
Many drugs originally approved for non-cancer conditions have shown unexpected anticancer activity in drug repurposing. For example, drugs such as arsenic trioxide use in cancer, thalidomide in cancer treatment, and all-trans retinoic acid repurposing have been repurposed successfully to treat various cancers like leukemia and multiple myeloma. Additionally, drugs like pantoprazole as anticancer agent, a proton pump inhibitor, and statins in head and neck cancer, typically used for gastric acid and cholesterol control respectively, are being explored for their ability to affect tumor growth and the tumor microenvironment in cancer therapy.
What tools help identify repurposing candidates?
The identification of candidate drugs for repurposing increasingly depends on advanced computational and experimental tools. Techniques such as molecular docking, network analysis, and big data analytics in drug discovery analyze drug-target interactions and disease signatures at a genomic and proteomic level. Experimental models, including 3D cultures like organoids and tumoroids, allow researchers to simulate the human tumor microenvironment more accurately for preclinical screening. This combined computational-experimental approach accelerates the discovery of new therapeutic uses for existing drugs, paving the way for quicker clinical testing and application.
This pragmatic and innovative approach holds great promise in expanding the arsenal against cancer while minimizing the time, cost, and risk traditionally associated with new drug development.
Key Molecular Targets and Mechanisms in Repurposed Cancer Drugs
How do repurposed drugs target cancer biology?
Repurposed drugs address several cancer hallmarks, including sustained proliferative signaling, evasion of cell death, induction of angiogenesis, invasion, and metastasis. They achieve this by modulating critical molecular pathways that regulate tumor growth and survival.
Cancer Hallmarks Targeted by Repurposed Drugs
- Sustained Proliferation: Repurposed agents can inhibit signals that drive uncontrolled cell division.
- Resisting Cell Death: Drugs promote apoptosis and autophagy to eliminate cancer cells.
- Inducing Angiogenesis: Some agents reduce new blood vessel formation, limiting tumor nutrient supply.
- Activating Invasion and Metastasis: Target molecules that facilitate cancer spread.
Signaling Pathways Involved
- PI3K/AKT/mTOR Pathway: Critical for cell growth and survival; drugs like metformin inhibit this pathway, suppressing proliferation and cancer stem cell renewal.
- Wnt/β-catenin Pathway: Important for stemness and metastasis; targeted by several repurposed drugs to hinder tumor progression.
- JAK/STAT Pathway: Involved in cell growth and immune evasion; inhibition can restore anti-tumor immunity.
Examples of Repurposed Drugs and Their Mechanisms
- Metformin: Activates AMPK and inhibits the PI3K/AKT/mTOR pathway, reducing tumor growth and affecting cancer stem cells.
- Disulfiram: Interferes with tumor metabolism by inhibiting glycolysis and enhancing oxidative stress.
- Salidroside: Inhibits cancer cell proliferation via downregulation of the PI3K/AKT signaling pathway.
These mechanisms allow repurposed drugs to impair cancer cell survival and metastasis, offering promising strategies that complement conventional therapies. Their ability to modulate multiple pathways enhances the potential to overcome drug resistance in cancer treatment.
Innovative Experimental Models in Drug Screening for Repurposing
What are the limitations of traditional 2D cell cultures?
Traditional two-dimensional (2D) cell cultures have been widely used for cancer drug screening but fall short in replicating the complex tumor microenvironment found in patients. These monolayer cultures lack the cell-to-cell and cell-to-matrix interactions crucial for tumor behavior, limiting their ability to mimic tumor heterogeneity, dynamics, and drug responses accurately. limitations of traditional cell cultures
How do 3D spheroids, organoids, and tumoroids improve tumor modeling?
Three-dimensional (3D) models such as spheroids, organoids, and tumoroids offer significant advantages over 2D cultures. They better emulate the architecture and microenvironment of human tumors by supporting more realistic cell interactions and gradients of oxygen and nutrients. This enables these models to capture features like proliferative, quiescent, and hypoxic zones within tumors. 3D tumor microenvironment models
- Spheroids: Simple, self-aggregated cell clusters that resemble tumor tissue and support multicellular interactions. spheroid models in cancer research
- Organoids and Tumoroids: Derived from patient tumors, these models preserve genetic and phenotypic heterogeneity, facilitating personalized drug screening and resistance mechanism studies. Patient-derived organoids Tumoroids in cancer research
Regulatory bodies including the FDA and EMA recognize 3D models as promising alternatives for preclinical testing, potentially reducing reliance on animal models and enhancing predictive accuracy. FDA and EMA on 3D preclinical testing models
What role do patient-derived xenografts (PDX) and hybrid models play?
Patient-derived xenografts remain the gold standard in preclinical cancer research due to their robust recapitulation of patient tumor biology. Hybrid models, combining PDX with organoids or cell cultures, integrate in vivo and in vitro insights. These approaches improve translational relevance and predictive power for drug repurposing by encompassing both tumor heterogeneity and microenvironmental factors. Patient-derived xenograft models
How are assays like the transwell assay used in drug repurposing studies?
The transwell assay is an in vitro technique employed to study cancer cell migration and metastasis potential. It measures the ability of cells to move through a membrane barrier, providing valuable data on how repurposed drugs influence invasive behaviors. This assay complements 3D models by offering a functional readout of drug effects on tumor aggressiveness and metastatic mechanisms. Transwell assay in cancer studies in vitro assays for tumor migration
These advanced experimental models and assays together represent a frontier in Cancer drug repurposing research overview, enabling more physiologically relevant screening and accelerating the identification of effective therapeutics.
Cutting-Edge Technologies Enhancing Drug Repurposing Efforts
How do AI, bioinformatics, and molecular biology contribute to identifying candidate drugs for repurposing?
Advances in artificial intelligence (AI), bioinformatics, and molecular biology have revolutionized the drug repurposing landscape by enabling high-throughput and precise identification of promising candidates. AI-driven algorithms analyze vast genomic and transcriptomic datasets to uncover novel drug–disease associations. Bioinformatics tools integrate omics data and molecular pathway analyses, facilitating screening of FDA-approved drugs for anticancer activity by predicting their effects on key oncogenic signaling pathways such as PI3K/AKT/mTOR and WNT/β-catenin. Molecular biology techniques further validate these findings by elucidating drug mechanisms at the cellular and molecular level.
What role does nanotechnology play in improving targeted drug delivery?
Nanotechnology offers innovative solutions that enhance the delivery of repurposed cancer drugs with greater precision and reduced side effects. Engineered nanocarriers improve pharmacokinetics and enable controlled release, improving therapeutic indices. Types of nanocarriers include liposomes, polymeric nanoparticles, and metallic nanoparticles, each designed to optimize drug loading and targeting.
How do nanocarriers like liposomes and polymeric nanoparticles improve efficacy and reduce toxicity?
- Liposomes encapsulate drugs within lipid bilayers, enhancing solubility and protecting drugs from degradation. They allow for targeted accumulation in tumors via enhanced permeability and retention (EPR) effect.
- Polymeric nanoparticles provide tunable degradation and release profiles, improving drug stability and sustained delivery.
Together, these platforms minimize systemic toxicity while maximizing anticancer efficacy, particularly for drugs with narrow therapeutic windows, as reviewed in Drug repurposing and nanotechnology for cancer therapy.
What emerging technologies are helping to reduce reliance on animal testing?
Organ-on-a-chip platforms represent a promising frontier that simulates human tumor physiology more accurately than traditional 2D cultures or animal models. These microfluidic devices reproduce tissue–tissue interfaces and dynamic conditions of the tumor microenvironment, allowing better predictive assessments of drug efficacy and toxicity. Integration with 3D spheroids and patient-derived organoids further advances personalized testing, aligning with ethical goals of reducing animal experimentation.
By combining computational power, advanced delivery systems, and sophisticated in vitro models, these technological innovations are accelerating the development and clinical translation of repurposed drugs in oncology.
Promising Repurposed Drugs and Their Emerging Roles in Cancer Therapy
What are some notable examples of repurposed drugs used in cancer therapy?
Several well-known drugs initially approved for non-cancer indications have demonstrated anticancer properties. These include thalidomide, widely used for multiple myeloma; arsenic trioxide, effective in certain leukemias; and all-trans retinoic acid (ATRA), also used in leukemia treatment. Additionally, the antipsychotic chlorpromazine has exhibited effects such as decreasing cancer cell growth and inducing apoptosis in cancers like glioblastoma and leukemia. The antifungal agent clotrimazole disrupts key cancer cell metabolism pathways and promotes apoptosis across multiple cancer types.
Are there other drug categories with anticancer potential?
Yes, antibiotics and antipsychotics have gained attention for their anticancer effects. Repurposed antibiotics are being explored for mechanisms that affect cancer growth and survival. Antipsychotics—including drugs such as haloperidol, trifluoperazine, and thioridazine—have shown promising results in inducing cell cycle arrest, autophagy, and apoptosis in tumor cells, and in some cases improving sensitivity to chemotherapy or radiotherapy.
What initiatives support drug repurposing research?
Projects like the ReDO (Repurposing Drugs in Oncology) Project prioritize candidate drugs based on existing clinical data and promote their investigation in cancer therapy. This international collaboration aims to accelerate clinical trials, gather dispersed evidence, and make effective low-toxicity treatments available sooner and affordably.
How are proton pump inhibitors being repurposed in cancer treatment?
Proton pump inhibitors like pantoprazole, traditionally used to reduce stomach acidity, are being investigated as adjuvants in cancer therapy. Pantoprazole can help inhibit tumor acidity, which is linked to cancer progression and treatment resistance, and may promote autophagy and apoptosis in tumor cells. These emerging uses offer novel ways to target the tumor microenvironment.
Repurposing drugs such as these offers a cost-effective, faster route to novel cancer treatments by leveraging known safety profiles while expanding therapeutic options.
Targeting Cancer Stem Cells through Drug Repurposing
What role do cancer stem cells play in metastasis, recurrence, and drug resistance?
Cancer stem cells (CSCs) are a critical subpopulation within tumors responsible for driving cancer progression, metastasis, and relapse. These cells exhibit self-renewal and differentiation capabilities, enabling them to regenerate the tumor. CSCs are often resistant to conventional treatments, contributing to drug resistance and disease recurrence. Cancer stem cells and cancer progression
Which signaling pathways regulate CSCs?
Key signaling pathways involved in CSC regulation include the Wnt/β-catenin, Notch, Hedgehog (Hdhg), and TGF-β pathways. These pathways control CSC self-renewal, differentiation, and interactions with the tumor microenvironment, facilitating tumor growth and metastasis. Cancer stem cells (CSCs)
What are some repurposed drugs targeting CSCs?
Several FDA-approved drugs originally used for non-cancer conditions have demonstrated activity against CSCs:
- Aspirin: Interferes with CSC survival and inflammation that supports the niche.
- Metformin: Inhibits CSC renewal by activating AMPK and suppressing Wnt signaling.
- Chloroquine: Disrupts autophagy in CSCs, sensitizing them to therapy.
- All-trans retinoic acid: Promotes differentiation of CSCs, reducing stemness.
- Disulfiram and Niclosamide: Target key metabolic pathways and CSC signaling.
Cancer stem cells and drug repurposing to target CSCs
Why are combination therapies important?
Combining repurposed drugs that target CSCs with conventional chemotherapeutics or targeted agents can be more effective. This approach aims to eradicate both the bulk tumor cells and the CSC population, reducing the risk of relapse and metastasis. Incorporation of micronutrients like vitamins A, C, and D or phytochemicals can further enhance treatment outcomes by disrupting CSC signaling and promoting cancer cell death.
This strategy leverages the known safety profiles of repurposed drugs to accelerate development timelines and reduce costs while addressing major obstacles in cancer therapy related to CSC-driven resistance and disease progression. Drug repurposing for cancer therapy
Addressing Tumor Microenvironment with Repurposed Compounds
How do repurposed drugs modulate the tumor microenvironment?
Repurposed drugs have been investigated for their abilities to alter various components of the tumor microenvironment (TME), which plays a pivotal role in cancer progression and resistance. These drugs can modulate the immune microenvironment by affecting immune cell infiltration and function, influence hypoxia conditions within tumors, regulate extracellular acidity, and impact stromal cell interactions. By modifying these factors, repurposed agents can inhibit tumor growth and metastasis.
Which repurposed drugs are used to alter the TME?
Several non-cancer drugs have shown promise in TME modulation:
- Beta blockers reduce inflammation and alter adrenergic signaling that supports tumor growth.
- Statins inhibit cholesterol biosynthesis pathways, interfering with tumor metabolism and potentially suppressing angiogenesis.
- Proton pump inhibitors (PPIs) like pantoprazole can neutralize tumor acidity, thereby affecting cancer cell survival and drug response.
What is the impact on angiogenesis, metabolism, and inflammation?
Repurposed drugs affect key TME processes:
- Angiogenesis inhibition restricts blood supply critical for tumor survival.
- Metabolic modulation disrupts cancer cell energy sources, enhancing apoptosis.
- Anti-inflammatory effects reduce tumor-promoting cytokines and immune suppression.
How does nanotechnology improve delivery to TME components?
Advanced nanocarrier systems—such as liposomes, polymeric, and metallic nanoparticles—are engineered to enhance the targeting and bioavailability of repurposed drugs within the TME. These platforms improve drug accumulation in tumor tissue, minimize systemic toxicity, and can overcome resistance mechanisms by facilitating controlled release and improved penetration into stromal and immune compartments.
This multifaceted approach combining TME-targeted repurposed drugs and nanotechnology holds significant promise for improving cancer therapeutic outcomes by disrupting the supportive niche tumors rely on.
Challenges and Barriers in Drug Repurposing for Oncology
What pharmacological issues complicate drug repurposing in cancer?
Drug repurposing in oncology faces challenges related to pharmacology, including achieving effective dosing and managing toxicity. Although repurposed drugs have known safety profiles from their original indications, cancer treatments often require higher or different dosages, leading to unexpected side effects. Managing these toxicities while maintaining therapeutic efficacy is a key hurdle, especially since some repurposed drugs may interfere with complex cancer pathways differently than in their original use.
How do regulatory and patent barriers affect repurposed cancer drugs?
Regulatory approval for new cancer indications of existing drugs involves extensive documentation and clinical evidence, which can be costly and time-consuming. Patent protections may have expired, reducing financial incentives for pharmaceutical companies to invest in costly trials. Additionally, navigating patent laws around drug repurposing can be complex, sometimes limiting commercial development despite promising clinical data. These challenges are well detailed in pharmacological challenges in drug repurposing.
Why is the complexity of cancer biology a challenge for repurposed drugs?
Cancer's biological complexity, including tumor heterogeneity and multiple resistance mechanisms, makes predicting repurposed drugs' effectiveness difficult. Tumors develop resistance through processes like drug efflux pumps, DNA repair, and signaling pathway alterations. Such mechanisms require that repurposed drugs either overcome these resistances or be combined with other therapies, complicating treatment design. Insights into these complexities are discussed in cancer stem cells and drug resistance mechanisms and signaling pathways in cancer.
Why are rigorous clinical trials necessary for repurposed drugs in cancer?
To confirm repurposed drugs' efficacy and safety in oncology, carefully designed clinical trials are essential. These studies help assess optimal dosing, identify side effects, and establish effectiveness in combination therapies that target multiple cancer hallmarks. Since cancer treatments often rely on multi-agent regimens, trials must explore synergistic drug interactions and resistance prevention strategies, ensuring reliable translation from laboratory findings to patient care. The importance of clinical testing and trial design in drug repurposing is discussed in drug repurposing for cancer therapy.
Hirschfeld Oncology’s Personalized Approach to Pancreatic Cancer Care
How does Hirschfeld Oncology's medical team approach pancreatic cancer care?
At the core of Hirschfeld Oncology's philosophy is a personalized treatment strategy tailored specifically for pancreatic cancer patients. Led by Dr. Azriel Hirschfeld, the team integrates multidisciplinary expertise to deliver care that blends both standard and cutting-edge therapies. Utilizing advanced diagnostics such as circulating tumor DNA and liquid biopsies, they precisely characterize tumor profiles to guide therapy choices.
The treatment regimens often combine low-dose metronomic chemotherapy with immunotherapy and targeted agents, aiming to balance efficacy with tolerability. This approach addresses drug resistance mechanisms and adapts to individual tumor biology, offering patients tailored options beyond conventional chemotherapy alone.
What role does advocacy play in Hirschfeld Oncology's cancer treatment philosophy?
Advocacy is a cornerstone of care at Hirschfeld Oncology. The team places great emphasis on educating patients about their disease and available treatments to foster informed decision-making. Emotional and psychosocial support is woven into the care continuum, recognizing the profound impact of cancer beyond its physical symptoms.
Additionally, Hirschfeld Oncology prioritizes facilitating patient access to innovative and breakthrough therapies, navigating regulatory and clinical trial landscapes to maximize treatment opportunities. This patient-centered advocacy ensures that individuals receive comprehensive support, empowering them through the complexities of pancreatic cancer management.
Innovative Therapeutic Strategies at Hirschfeld Oncology for Resistant Pancreatic Cancer
What innovative strategies is Hirschfeld Oncology using to redefine pancreatic cancer treatment?
Hirschfeld Oncology is pioneering new approaches to tackle resistant and metastatic pancreatic cancer by implementing low-dose combination chemotherapy regimens such as G-FLIP combined with Mitomycin C. This metronomic chemotherapy strategy administers continuous low doses of multiple agents, aiming to minimize toxicity while effectively suppressing tumor progression.
The center is actively engaging in clinical trials to evaluate the safety, treatment response, and survival benefits of these regimens in patients with advanced pancreatic cancer, providing crucial data on their therapeutic potential and tolerability.
Beyond chemotherapy, Hirschfeld Oncology explores combination therapies that integrate targeted agents and immunotherapies to overcome drug resistance and exploit multiple vulnerabilities of pancreatic tumors. This multimodal approach is designed to attack cancer cells from various angles, potentially enhancing treatment efficacy.
A significant aspect of their strategy includes the use of blood-based prognostic biomarkers for real-time monitoring of patient responses and guiding therapeutic decisions. These biomarkers help personalize treatment, enabling timely adjustments to maximize benefit and minimize adverse effects.
Together, these innovative methods reflect Hirschfeld Oncology's commitment to advancing pancreatic cancer treatment through personalized, multi-agent strategies that improve patient outcomes while addressing the challenges of resistance and toxicity.
Future Directions: Integrating Precision Medicine, Nanotechnology, and Combination Therapies
Emerging Trend of Combining Repurposed Drugs to Target Multiple Cancer Hallmarks
Cancer's complexity necessitates therapies that address various tumor behaviors simultaneously. Recent research highlights that repurposed drugs can be combined strategically to target multiple cancer hallmarks such as proliferative signaling, evasion of apoptosis, angiogenesis, and metastasis. This multi-targeted approach promises enhanced efficacy by interrupting diverse tumor survival mechanisms, reducing drug resistance, and preventing relapse. For instance, combinations involving metformin with immune modulators or anti-inflammatory repurposed drugs are under investigation to exploit complementary mechanisms.
Precision Medicine Approaches Utilizing Molecular Profiling and Biomarkers
The integration of molecular profiling and biomarker identification enables precise selection of repurposed drugs tailored to individual tumor characteristics. Techniques like deep genomic and transcriptomic analyses facilitate the identification of actionable mutations and cancer stem cell markers. These biomarkers inform clinicians about which repurposed agents may effectively disrupt specific pathways, ensuring personalized and more effective treatments while minimizing off-target effects (Advances in cancer research, Cancer stem cells and drug repurposing).
Advancement of Nanotechnology-Based Delivery Systems to Enhance Drug Targeting and Reduce Toxicities
Nanotechnology is revolutionizing the delivery of repurposed drugs by improving targeted delivery directly to tumors, thereby reducing systemic toxicity. Various nanoformulations including liposomes, polymeric nanoparticles, metallic nanoparticles, and ultrasmall-in-nano architectures have been developed (Nanotechnology in pancreatic cancer treatment, Drug repurposing nanocarriers and cancer therapy). These carriers enhance drug stability, bioavailability, and facilitate controlled release. Such systems not only improve therapeutic efficacy but also help overcome multidrug resistance and allow lower dosing schedules.
Potential of AI and Big Data Analytics to Optimize Drug Selection and Treatment Personalization
Artificial intelligence and big data analytics are emerging as transformative tools in drug repurposing. By integrating vast datasets from omics, drug screening, clinical outcomes, and molecular interactions, AI algorithms identify novel candidate drugs and optimal drug combinations (AI in oncology drug discovery, Drug repurposing and computational methods. This computational power accelerates hypothesis generation, predicts patient responses, and refines treatment personalization. However, real-world implementation is challenged by data accessibility and privacy issues, which are actively being addressed.
Together, these future directions emphasize a multi-disciplinary effort to enhance the clinical translation of drug repurposing in cancer therapy — driven by combinations that target cancer complexity, precision selection based on molecular insights, nanotechnological delivery innovations, and AI-augmented decision making.
The Economic and Clinical Imperative of Drug Repurposing in Cancer Care
Rising Costs of Novel Cancer Drugs and Financial Toxicities
The cost of cancer treatment has surged dramatically over recent decades. For instance, the annual cost for cancer drugs has increased from about $54,100 in 1995 to over $207,000 by 2013. Such steep price hikes outpace household income growth, leading to significant financial toxicity for patients. This economic burden often results in patients skipping doses or not filling their prescriptions, negatively affecting treatment outcomes and overall quality of life. For detailed analysis on financial toxicity and drug costs, see innovative new cancer drugs.
Drug Repurposing as a Cost-Effective Alternative Preserving Treatment Efficacy
Drug repurposing offers a promising, cost-effective alternative by utilizing FDA-approved drugs with known safety profiles for new cancer indications. This strategy reduces both development timelines and clinical trial costs, while maintaining or enhancing therapeutic efficacy. Examples include repurposed agents like thalidomide and arsenic trioxide, which successfully transitioned into oncology treatments. By bypassing early-stage development hurdles, repurposed drugs may provide affordable yet effective options for cancer care. Learn more about these advantages and examples in Drug repurposing for cancer therapy.
Importance of Multi-Stakeholder Collaboration to Improve Access and Affordability
Improving accessibility and affordability of cancer therapies requires coordinated efforts among drug developers, policymakers, payers, healthcare systems, and patients. Initiatives such as outcomes-based pricing models aim to align drug costs with their clinical value, promoting the use of high-value medications. Transparent communication about treatment options and associated costs further supports informed decision-making and patient empowerment. A comprehensive report on multi-stakeholder collaboration in cancer drug policy is available at rising cancer drug costs.
Potential for Repurposed Drugs to Expand Treatment Options in Resource-Limited Settings
Repurposed drugs offer significant potential to broaden cancer treatment availability, especially in low-resource settings where conventional novel therapies may be cost-prohibitive. By leveraging existing drugs with known profiles, healthcare providers can access more affordable, safe, and effective options. This approach can reduce disparities in cancer care worldwide, facilitating earlier and equitable access to life-saving treatments. For more on drug repurposing and affordable cancer drug development, see ReDO project and Drug repurposing for cancer therapy.
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