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Introduction to Drug Repurposing in Oncology
What Is Drug Repurposing?
Drug repurposing, also known as drug repositioning, is the strategy of finding new therapeutic uses for existing medications that are already clinically approved. Instead of developing new drugs from scratch, this approach explores how current drugs can be applied to treat different diseases, including cancer.
Why Choose Drug Repurposing?
This method offers several advantages over traditional drug development:
- Faster development timelines: Since repurposed drugs have established safety and pharmacokinetic profiles, they can often skip early-phase trials, speeding up availability.
- Cost-effectiveness: Developing entirely new drugs can cost billions and take over a decade, whereas repurposing reduces these resources significantly.
- Lower risk: Known safety profiles reduce the likelihood of unexpected adverse effects.
The Growing Role in Cancer Treatment
Cancer is a major global health challenge, with millions of new cases each year. Drug repurposing has emerged as a promising approach to accelerate the availability of effective therapies. It enables targeting multiple cancer hallmarks, such as cell proliferation, tumor microenvironment, and immune evasion, while often complementing existing treatments. This strategy not only expedites new options but also improves affordability and accessibility of cancer care worldwide.
Overview of Drug Repurposing and Its Strategic Benefits in Cancer Care
What is drug repurposing in cancer therapy?
Drug repurposing involves finding new therapeutic uses for existing, clinically approved drugs. Instead of developing a drug from scratch, repurposing leverages medications already approved for other diseases, making new cancer treatments available faster. This approach relies on re-evaluating known drugs against cancer pathways and mechanisms (Drug repurposing for cancer therapy, Drug repurposing for cancer therapy).
Why is drug repurposing cost-effective and faster?
Because repurposed drugs have well-known safety, toxicity, and pharmacokinetic profiles, the time and expense of drug development are significantly reduced. Traditional drug development often takes over a decade and costs billions, while repurposing can cut this to a few years and lower costs, making treatments more accessible and affordable (Advantages of drug repurposing, Drug repurposing in cancer treatment).
How does using established drugs reduce risk?
Drugs already approved for human use have passed extensive safety trials. This familiarity decreases risks related to toxicity or unforeseen side effects, enabling researchers and clinicians to focus more on therapeutic efficacy rather than safety concerns (FDA-approved drugs for new cancer uses, Drug repurposing benefits).
What are some successful examples?
- Arsenic trioxide: Originally used for other diseases, this drug has been successfully repurposed for treating acute promyelocytic leukemia, improving patient outcomes dramatically (Arsenic trioxide and retinoic acid for leukemia).
- Thalidomide: Initially infamous for its side effects, thalidomide was repurposed effectively to treat multiple myeloma and leprosy due to its immunomodulatory and anti-angiogenic properties (Thalidomide uses in leprosy and myeloma, Thalidomide repurposed for multiple myeloma).
These cases highlight the potential of drug repurposing to transform cancer care by rapidly bringing effective treatments to patients with lower development costs and risks (Examples of repurposed drugs for cancer, Drug repurposing in cancer treatment).
Targeting Cancer Hallmarks with Repurposed Drugs
What Are the Hallmarks of Cancer and How Can They Be Targeted?
Cancer is characterized by specific biological capabilities known as hallmarks of cancer and drug repurposing, which include sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, deregulated metabolism, angiogenesis, and enhanced invasion and metastasis. These hallmarks serve as therapeutic targets for cancer treatment. Repurposed drugs—originally approved for other diseases—offer promising strategies to interfere with these critical cancer processes, often with established safety profiles that expedite clinical application.
How Do Repurposed Drugs Inhibit Cancer Cell Proliferation?
Sustained proliferative signaling is a key hallmark driving tumor growth. Repurposed drugs target signaling pathways such as PI3K/AKT and mTOR, which regulate cell division and survival. For example, drugs like metformin modulate these pathways and reduce proliferative signals, slowing cancer progression effectively. By disrupting these molecular pathways, repurposed drugs inhibit tumor growth without the need for developing entirely new compounds.
In What Ways Do Repurposed Drugs Induce Tumor Cell Death?
Induction of tumor cell death, such as apoptosis, pyroptosis, and autophagy, is vital for eliminating cancer cells. Repurposed agents can activate these death pathways selectively in tumor cells. For instance, arsenic trioxide triggers apoptosis in acute promyelocytic leukemia (arsenic trioxide and retinoic acid for leukemia, while disulfiram generates oxidative stress leading to cell death in breast cancer. Such mechanisms help overcome resistance to conventional therapies.
How Are Tumor Metabolism and Growth Suppressors Modulated by Repurposed Drugs?
Cancer cells often reprogram metabolism to support unchecked growth. Repurposed drugs like leflunomide and disulfiram inhibit metabolic enzymes to starve tumors. Additionally, drugs such as statins can reactivate growth suppressor pathways, including p53, restoring control over abnormal cell proliferation. These dual actions reduce tumor viability and enhance responsiveness to treatments.
How Do Repurposed Drugs Affect Angiogenesis, Invasion, and Metastasis?
Tumors require new blood vessel formation (angiogenesis) and possess the ability to invade and spread. Repurposed drugs such as artemisinin inhibit angiogenesis by targeting vascular endothelial growth factors (examples of repurposed drugs for cancer). Anthelmintics like mebendazole disrupt microtubules, blocking cancer cell invasion and metastasis. By intervening in these processes, repurposed drugs suppress tumor progression and dissemination.
This multi-faceted approach using repurposed drugs offers an efficient and cost-effective strategy to target diverse cancer hallmarks, complementing existing therapies and improving patient outcomes.
Repurposed Drugs Targeting the Tumor Microenvironment (TME)
What is the Role of the Tumor Microenvironment (TME) in Cancer Progression?
The tumor microenvironment (TME) is a complex network surrounding cancer cells that significantly influences tumor growth, metastasis, and response to therapies. It consists of various cellular and non-cellular components that interact with cancer cells to promote survival and immune evasion. For detailed insights, see Tumor microenvironment components and Tumor microenvironment targeting.
What are the Components of the Tumor Microenvironment?
The TME includes:
- Immune cells: such as tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) that can suppress antitumor immunity.
- Hypoxia: low oxygen areas that induce adaptation promoting cancer progression.
- Acidity: localized acidic conditions that affect drug efficacy and immune cell function.
- Metabolic factors: abnormal metabolism creating a supportive niche.
- Microbiota: microbial populations influencing immune responses and inflammation.
- Mechanical forces: physical stresses altering cell behavior.
For comprehensive information, refer to Tumor microenvironment components and further discussions on tumor microenvironment modulation.
What are Examples of Repurposed Drugs that Modulate the TME?
Several existing drugs have been identified to influence the TME to restrain cancer progression:
- Apigenin: a natural flavonoid that modulates immune responses within the TME.
- Celecoxib: a nonsteroidal anti-inflammatory drug (NSAID) that inhibits inflammation and suppresses pro-tumoral factors.
- Metformin: an antidiabetic agent that affects phenotypic plasticity and tumor metabolism.
- Beta blockers (e.g., propranolol): modulate the innervated niche, reducing stress-related tumor growth.
These examples are highlighted in Examples of drugs targeting the tumor microenvironment and Drug repurposing for cancer therapy.
How Do These Drugs Impact Tumor Growth and Enhance Immunotherapy?
By targeting the TME, these repurposed drugs:
- Inhibit pro-tumor inflammation and angiogenesis.
- Reactivate antitumor immunity by reversing immune suppression.
- Modify metabolic conditions unfavorable for cancer cell survival.
- Enhance the efficacy of immunotherapies, such as immune checkpoint inhibitors, by creating a more permissive immune microenvironment.
For detailed mechanisms and clinical perspectives, see Tumor microenvironment targeting, Cancer immunotherapy strategies, and Drug repurposing for cancer therapy.
Employing repurposed drugs that modulate the TME holds promise for improving treatment outcomes and overcoming resistance in various cancers.
Innovative Approaches: Integrating Nanotechnology with Drug Repurposing
How do nanocarriers improve drug delivery and bioavailability?
Nanocarriers enhance the delivery of repurposed drugs by improving their stability, solubility, and pharmacokinetics. This allows drugs to reach tumor sites more effectively while maintaining potency. By protecting drugs from premature degradation, nanocarriers enable sustained release and improved absorption, boosting therapeutic effects in cancer treatment (Nanocarriers in cancer drug delivery, Nanomaterial-based drug delivery for repurposed drugs, Nanomedicine in cancer treatment).
What types of nanomaterials are used in drug repurposing for cancer therapy?
Common nanocarriers include:
- Liposomes: Biocompatible vesicles that encapsulate drugs, facilitating targeted delivery and reducing systemic toxicity (Liposomes in drug delivery, Liposomal inorganic polymeric nanocarriers).
- Polymeric Nanoparticles: Synthetic or natural polymers forming particles that control drug release and improve circulation time (Polymeric nanocarriers for cancer, Polymeric nanoparticles).
- Metallic Nanoparticles: Metal-based particles with customizable surfaces that enable active targeting and enhanced cellular uptake (Metallic nanoparticles in cancer therapy, Metallic nanoparticles).
These nanomaterials can be functionalized with ligands or antibodies for precise tumor targeting (Examples of drugs targeting the tumor microenvironment, Targeting the tumor microenvironment).
What are the benefits of integrating nanotechnology with drug repurposing?
- Targeted Delivery: Nanocarriers concentrate drugs at the tumor site, minimizing exposure to healthy tissues (Targeted nanoparticle therapy, Nanocarriers in drug delivery).
- Reduced Side Effects: By limiting systemic distribution, nanotechnology helps avoid off-target toxicity (Nanocarriers improving drug efficacy).
- Overcoming Pharmacokinetic Barriers: Nanomaterials improve drug solubility and stability, enhancing bioavailability of repurposed drugs that otherwise suffer from poor pharmacokinetics (Enhancing drug efficacy with nanocarriers, Nanotechnology nanoformulations).
- Enabling Combination Therapies: Nanocarriers can co-deliver multiple repurposed drugs or combine them with immunotherapies to improve efficacy (Combination immune checkpoint inhibitor therapies, Repurposed drugs in combination therapy).
What are examples of nanotechnology-enabled drug repurposing platforms?
Research has demonstrated enhanced cancer treatment using nanocarriers loaded with repurposed drugs such as:
- Liposomal formulations delivering metformin or disulfiram to improve targeting and reduce toxicity (Nanocarriers in cancer drug delivery, Repurposed drugs effective in cancer).
- Polymeric nanoparticles carrying non-oncology drugs to induce apoptosis and inhibit tumor growth (Nanomedicine in cancer treatment, Nanocarriers improving drug efficacy.
- Metallic nanoparticles conjugated with repurposed agents for improved penetration into tumor microenvironment (Metallic nanoparticles in cancer therapy, Drug repurposing combined with nanotechnology).
These platforms show promise in clinical translation by enhancing the effectiveness and safety profile of repurposed cancer drugs (Nanomaterial-based drug delivery for repurposed drugs, Innovative approaches for cancer treatment).
Repurposed Drugs in Cancer Stem Cell (CSC) Targeting and Resistance Overcoming
Why are Cancer Stem Cells important in cancer progression and relapse?
Cancer stem cells (CSCs) play a crucial role in cancer by driving tumor growth, metastasis, and recurrence. They are often resistant to conventional treatments, which can lead to disease relapse even after initial therapy. CSCs possess self-renewal and differentiation abilities, making them a persistent source of cancer cells and therapeutic challenge (Cancer stem cells in cancer progression, Targeting cancer stem cells, drug repurposing targeting cancer stem cells (CSCs), drug repurposing targeting cancer stem cells (CSCs)).
What signaling pathways regulate CSCs?
Several key pathways regulate CSC behavior, including:
- Wnt/β-catenin pathway
- Notch signaling
- Hedgehog (Hdhg) pathway
- Transforming growth factor-beta (TGF-β) pathway
These signaling networks maintain CSC properties and contribute to their resistance by promoting survival, proliferation, and evasion of apoptosis (Signaling pathways in cancer stem cells, Drug repurposing for cancer therapy, drug repurposing targeting cancer stem cells (CSCs).
Examples of repurposed drugs targeting CSCs
Numerous existing drugs with known safety profiles have shown promise in targeting CSCs and overcoming resistance:
- Aspirin: Modulates inflammatory pathways impacting CSC niche and signaling.
- Metformin: Influences metabolism and AMPK activation, inhibiting CSC proliferation.
- All-trans retinoic acid (ATRA): Promotes CSC differentiation and decreases stemness.
Other repositioned drugs like valproic acid, ivermectin, and disulfiram also modulate pathways critical to CSC survival (FDA-approved drugs targeting CSCs, Drug repurposing advantages, Examples of repurposed drugs for cancer, drug repurposing for cancer therapy.
How can efficacy be improved via combination therapies?
Combining repurposed drugs with standard treatments or with each other can enhance therapeutic effects. Such combinations may:
- Target multiple CSC-related pathways simultaneously
- Reduce chemoresistance
- Lower required doses, minimizing toxicity
- Improve outcomes by preventing CSC-driven relapse
(see Combination therapies in drug repurposing, Clinical trials on repurposed cancer drugs).
What is the status of preclinical and clinical research?
Preclinical studies have demonstrated that repurposed drugs effectively reduce CSC populations and inhibit tumor growth in models. Clinical trials are underway investigating these agents alone or in combinations, focusing on safety and efficacy in diverse cancer types. Ongoing research continues to validate their potential as part of integrated cancer treatment paradigms (Clinical trials on repurposed cancer drugs, Translational research in drug repurposing).
Enhancing Immunotherapy through Drug Repurposing Strategies
Current challenges with cancer immunotherapy
Cancer immunotherapy, including immune checkpoint inhibitors (ICIs), CAR-T cell therapy, and tumor vaccines, has revolutionized cancer treatment but faces significant challenges. Many patients show limited or no response due to tumor intrinsic factors such as genomic instability, tumor microenvironment-induced immune suppression, and immune evasion mechanisms. Factors like extracellular matrix stiffness, immunosuppressive cells, and hypoxia within the tumor microenvironment (TME) further reduce immunotherapy efficacy. For more details, see Cancer immunotherapy strategies and tumor microenvironment impact.
Drugs improving immune checkpoint inhibition efficacy
Repurposed drugs such as metformin have demonstrated the ability to enhance immune checkpoint blockade by modulating proteins like PD-L1. Additionally, non-oncology drugs like beta blockers and anti-inflammatory agents improve the immune system's ability to respond by reversing tumor-induced immunosuppression. These agents work by downregulating pro-tumor signaling pathways and promoting effector T-cell activation. Learn more about Enhancing immunotherapy with repurposed drugs and Drug repurposing in cancer therapy mechanisms.
Modulating immune microenvironment with repurposed agents
Drugs like celecoxib, an anti-inflammatory COX-2 inhibitor, target inflammation in the TME, reducing protumor inflammatory cytokines. Apigenin, a flavonoid, modulates immune cell function, enhancing antitumor immunity. Other repurposed drugs aim to alter metabolic and hypoxic niches within the TME, improving immune cell infiltration and function. These approaches are discussed in Tumor microenvironment targeting and repurposed drugs and Drug repurposing for cancer therapy.
Phytochemicals and natural products in immune response modulation
Natural compounds such as QS-21, paclitaxel, curcumin, and epigallocatechin gallate (EGCG) have immunomodulatory effects. They enhance antigen presentation, promote dendritic cell maturation, inhibit immune checkpoints like PD-1/PD-L1, regulate the microbiome, and remodel the TME to be less suppressive. Nanotechnology-based delivery systems improve their bioavailability and therapeutic index. Refer to Phytochemicals in cancer immunotherapy and nanotechnology delivery systems and Nanocarriers in cancer drug delivery.
Synergy of immunotherapy and repurposed drugs
Combining immunotherapies with repurposed drugs creates synergistic anti-cancer effects. These combinations enhance tumor antigen recognition, reduce resistance mechanisms, and stimulate durable immune memory. Clinical trials are exploring such combinations to increase response rates and extend patient survival, highlighting repurposing’s crucial role in next-generation cancer immunotherapy. For further insights, see Enhancing immunotherapy with repurposed drugs and Cancer immunotherapy strategies and tumor microenvironment impact.
Computational and Bioinformatics Advances Facilitating Drug Repurposing
Use of AI, Machine Learning, and Big Data Analytics
Artificial intelligence (AI) and machine learning (ML) have become pivotal in streamlining drug repurposing. By analyzing large datasets, these technologies uncover hidden patterns and predict new therapeutic uses for existing drugs more efficiently than traditional methods. AI helps integrate diverse data types—from drug-target interactions to genomic profiles—enhancing prediction accuracy and reducing the discovery timeline. For further details on AI-driven drug repurposing methods and machine learning for drug discovery in cancer.
In Silico Screening, Molecular Docking, and Network Pharmacology
Computational methods such as in silico screening and molecular docking simulate drug-target interactions virtually, identifying promising candidates for repurposing. Network pharmacology examines complex interactions within biological systems to reveal how drugs may modulate multiple disease pathways simultaneously. These approaches facilitate hypothesis generation to select drugs likely to impact cancer-related targets. More on computational approaches in drug repurposing and network pharmacology for disease pathways.
Systems Biology and Transcriptome Analysis for Target Discovery
Systems biology combines multi-omics data to model cellular networks and disease mechanisms, aiding identification of novel drug targets. Transcriptome profiling compares gene expression patterns in diseased versus healthy states to pinpoint pathways for therapeutic intervention. These analyses provide a rich framework to discover repurposed drugs that can modulate dysregulated cancer pathways effectively. Detailed insights into these methods and their role in drug repurposing are available at systems biology in cancer drug repurposing and transcriptome analysis in GIST.
Examples of Computational Frameworks and Algorithms
Notable computational tools include the KUALA framework, which classifies kinase inhibitors and predicts their targets using multiple ML algorithms. CavitomiX employs active site cavity comparison to identify inhibitors, even revealing antiviral properties of approved drugs. Additionally, algorithms like GPSnet predict patient-specific drug responses, demonstrating personalized repurposing strategies. These exemplify how sophisticated computational platforms accelerate drug repositioning in oncology. For more information on these computational frameworks, see KUALA and CavitomiX frameworks and GPSnet algorithm for drug response prediction.
Repurposing Chronically Used Medications: Anti-Diabetics and Anti-Hypertensives
What is the epidemiological link between chronic diseases and cancer?
Chronic conditions like diabetes and hypertension are associated with an increased risk of several cancers. Shared biological pathways, such as inflammation and altered metabolism, contribute to this link, making drugs for these chronic diseases promising candidates for drug repurposing in cancer therapy.
How do metformin and pioglitazone work in cancer therapy?
Metformin, a widely used anti-diabetic, acts by activating AMPK and inhibiting mTOR pathways, leading to reduced tumor cell proliferation and metastasis. Pioglitazone similarly influences cancer cell growth by modulating cell cycle arrest and promoting apoptosis, showing anti-cancer effects across various tumor types (drug repurposing in cancer therapy).
What role do beta blockers like propranolol play in cancer treatment?
Beta blockers, primarily used for hypertension, have demonstrated anti-cancer properties by inducing apoptosis, downregulating survival signaling pathways, and inhibiting angiogenesis. Propranolol, notably, is under evaluation in multiple cancers including neuroblastoma and breast cancer for its ability to improve therapeutic outcomes (drug repurposing in cancer treatment.
What clinical trials and evidence support these repurposed drugs?
Over 90 clinical trials have assessed anti-diabetic and anti-hypertensive drugs for cancer therapy. Metformin has shown reduced risk and improved survival in colorectal, breast, pancreatic, prostate, lung, and cervical cancers. Beta blockers like propranolol have reached phase IV trials indicating promising efficacy. Despite variable results, these drugs offer safer, cost-effective options to complement existing cancer treatments (drug repurposing in cancer therapy, Winship Cancer Institute drug repurposing studies.
These chronically used medications illustrate how understanding shared disease mechanisms can accelerate cancer therapy development through drug repurposing. Their established safety profiles and ongoing clinical validation make them valuable additions to the expanding arsenal against cancer.
Clinical Trials and Challenges in Translating Repurposed Drugs into Practice
Why Are Clinical Trials Crucial for Repurposed Drugs?
Clinical trials are essential to prove that repurposed drugs are effective and safe for their new cancer indications. Although these drugs have established safety profiles from previous uses, cancer treatments often require different dosing or combinations that must be carefully evaluated. Robust clinical evidence helps ensure therapeutic benefits while monitoring for unexpected side effects (Drug repurposing in cancer therapy, drug repurposing in cancer treatment.
What Regulatory Pathways Support Repurposed Cancer Drugs?
The 505(b)(2) regulatory pathway in the U.S. is a common route for approval of repurposed drugs. It allows relying on existing safety and pharmacokinetic data, which can significantly shorten development time and reduce costs. However, demonstrating clinical efficacy for the new indication remains mandatory (Drug Repurposing in Modern Medicine, drug repurposing in cancer therapy).
What Barriers Hinder the Translation of Repurposed Drugs?
Significant challenges include limited funding, as pharmaceutical companies might be less motivated to invest in drugs without strong patent protection or high commercial returns. Intellectual property issues can also discourage development due to difficulties securing exclusivity. Additionally, regulatory hurdles and a fragmented approach to clinical trial design impede progress (Drug Repurposing of Generic Drugs, drug repurposing benefits).
How Can These Challenges Be Overcome?
Strategies to enhance repurposing success involve fostering global collaborations among academia, industry, government bodies, and nonprofit organizations to pool expertise and resources. Dedicated funding mechanisms and regulatory incentives can mitigate financial risks. Innovative clinical trial designs tailored for repurposed drugs and open data sharing promote efficiency. Advocacy and policy efforts are crucial to raise awareness and support for repurposing initiatives, particularly to ensure equitable access worldwide (Drug repurposing in cancer care, collaborative drug repurposing initiatives).
Global Equity and Accessibility: The Role of Drug Repurposing in Low- and Middle-Income Countries
Disparities in cancer care and clinical trial representation
Cancer care faces significant disparities globally, with low- and middle-income countries (LMICs) often underrepresented in research and clinical trials. Despite bearing a high burden of cancer mortality, these regions have limited access to novel treatments. Clinical trials predominantly occur in high-income countries, which may not reflect the genetic diversity or healthcare infrastructure of LMIC populations. This underrepresentation limits the applicability of findings and perpetuates inequality in cancer outcomes (Drug repurposing in cancer treatment; Global disparities in cancer care; Underrepresentation of LMICs in clinical trials.
Advantages of repurposed drugs for affordability and availability
Drug repurposing leverages existing, off-patent medicines with established safety profiles, offering cost-effective treatment options that are more accessible for LMICs. These drugs often bypass early-phase trials, reducing development time and expense. Their established manufacturing processes ensure broader availability, and generic formulations further enhance affordability. Such drugs can fill critical gaps in cancer care by providing well-tolerated, effective therapies without the prohibitive costs associated with new drugs (Drug repurposing and health equity; Affordable cancer treatments through repurposing; Shortening drug development timelines.
Regulatory and funding support mechanisms
To maximize impact in LMICs, supportive regulatory frameworks are needed to facilitate approval and registration of repurposed medicines. Dedicated funding mechanisms, such as surcharges on generic drug sales or grants from public and charitable organizations, can support essential clinical trials and infrastructure development. Streamlined policies combat patent evergreening practices that limit access, ensuring that repurposed drugs can be widely distributed without commercial barriers (Regulatory hurdles in repurposing; Patent standards and repurposing; Funding mechanisms for drug repurposing.
Advocacy and policy strategies to expand access
Global advocacy efforts highlight the human right to health and emphasize the importance of affordable cancer treatment. Policies that promote investigator-led trials in LMICs and support open-access data sharing enhance local research capacity and relevance. Educational campaigns raise awareness about the benefits of drug repurposing, encouraging uptake by healthcare providers and policy-makers. These combined actions help reduce treatment inequities and broaden the availability of effective cancer therapies worldwide (Advocacy for drug repurposing research; Expanding research in diverse populations; Investigator-led trials in LMICs; Ensuring equity in cancer drug repurposing.
Future Perspectives: Integrating Precision Oncology, Drug Repurposing, and Innovative Therapies
How can genomic profiling and drug repurposing be combined for personalized cancer treatment?
Precision oncology leverages detailed genomic profiling of individual tumors to identify specific mutations and pathways driving cancer progression. This data allows for the strategic use of repurposed drugs targeting cancer hallmarks and utilizes systems biology in cancer drug repurposing where computational and bioinformatics tools analyze omics data to uncover new drug-target relationships. These methods enable existing drugs with known safety profiles to be matched to patient-specific molecular signatures. Such an approach not only expedites therapy selection but also reduces development costs and timelines, offering tailored treatments with potentially improved efficacy and tolerability (Drug repurposing in cancer therapy.
How do repurposed drugs integrate with targeted therapies, immunotherapy, and nanomedicine?
Repurposed drugs can augment the effectiveness of targeted therapies by modulating multiple cancer hallmarks like proliferation, angiogenesis, and metastasis (repurposed drugs targeting cancer hallmarks. When combined with immunotherapies, repurposed agents such as metformin can enhance immune checkpoint blockade by promoting antitumor immunity or modifying the tumor microenvironment (Tumor microenvironment and immunotherapy). Nanotechnology further amplifies this synergy by encapsulating repurposed drugs within nanocarriers—like liposomes and polymeric nanoparticles—to optimize delivery, increase tumor specificity, improve bioavailability, and minimize systemic toxicities. This integration creates multifaceted regimens that adapt to tumor complexity and resistance mechanisms (Nanomaterial-based drug delivery for repurposed drugs.
What role do emerging modalities such as antibody-drug conjugates (ADCs) and CAR-T therapies play alongside repurposed drugs?
Emerging modalities such as antibody-drug conjugates (ADCs) and CAR-T cell therapies represent precision approaches targeting cancer cells or harnessing immune responses. ADCs deliver cytotoxic agents directly into cancer cells expressing specific antigens, potentially combined with repurposed drugs that alter tumor metabolism or microenvironment to sensitize cells for targeted killing. Similarly, CAR-T therapies can benefit from drugs that modulate immune components or reduce immunosuppressive barriers. Combining repurposed drugs with these innovative therapies may improve efficacy, overcome resistance, and expand applicability across various cancers (combination cancer therapies).
How are physician-led innovative practices, exemplified by Dr. Azriel Hirschfeld, advancing these integrated approaches?
Physician innovators like Dr. Azriel Hirschfeld, MD champion personalized, compassionate cancer care by integrating molecular profiling, liquid biopsies, and innovative off-label or repurposed therapies. Their approach involves low-dose combination chemotherapy, targeting resistant tumors with a blend of established and repurposed drugs tailored to molecular insights. This multidisciplinary strategy, combined with continuous patient advocacy and research into treatment resistance, exemplifies how frontline clinicians facilitate translation of drug repurposing and novel therapies into practical, individualized treatment paradigms, advancing precision oncology beyond theoretical frameworks (innovative cancer therapies by Dr. Hirschfeld).
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