Drug Repurposing in Cancer Treatment: Exploring Case Studies and Revolutionary Approaches  

*Ajinkya Kumar, ¹Vivek Singh
*Research Scholar, Rajasthan Pharmacy College, Jaipur
¹Research Scholar, Rajasthan Pharmacy College, Jaipur

Article Details

Title: Drug Repurposing in Cancer Treatment: Exploring Case Studies and Revolutionary Approaches

Authors: Ajinkya Kumar, Vivek Singh

Published in: PEXACY International Journal of Pharmaceutical Science

Volume/Issue: 2(12)

Pages: 33-46

Publication Date: 02/12/2023

DOI: 10.5281/zenodo.10250287

ISSN: 2584-024X

Language: English

Publisher: PEXACY International Journal of Pharmaceutical Science

PDF Download: Access Full Paper

Abstract: This review article explores the innovative realm of drug repurposing in Cancer, highlighting various case studies where non-cancer drugs have shown potential in cancer treatment. Through an examination of drugs like Metformin, Thalidomide, Ivermectin, and others, the article illustrates how these repurposed drugs can offer novel therapeutic options, potentially enhancing efficacy and reducing side effects in cancer treatment. The discussion encompasses the efficacy, mechanisms, challenges, and future directions of these drugs in oncology, emphasizing the importance of personalized medicine, economic considerations, and ethical implications. The case studies reveal the diverse mechanisms through which these drugs exert anti-cancer effects, ranging from inhibiting key signaling pathways to enhancing the effects of existing cancer therapies. The review also addresses the regulatory, financial, and clinical trial challenges in this field, suggesting the need for more robust research and strategic integration into current treatment protocols.

Keywords: Drug Repurposing, Oncology, Cancer Treatment, Metformin, Thalidomide, Ivermectin, Personalized Medicine, Clinical Trials, Pharmacoeconomics, Ethical Considerations.
Article can be accessed online on: PEXACY International Journal of Pharmaceutical Science
DOI: 10.5281/zenodo.10250287
Corresponding Author- *Ajinkya Kumar
Update: Received on 27/11/2023; Accepted; 29/11/2023, Published on; 02/12/2023

INTRODUCTION

The landscape of oncology is undergoing a transformative shift with the advent of drug repurposing, a strategy that breathes new life into existing medications by targeting them against cancer. This approach, rooted in the reevaluation of drugs approved for other diseases, has opened up a novel and efficient pathway in cancer treatment. The rationale behind drug repurposing in oncology stems from the urgent need to find effective, safe, and cost-efficient treatments amidst the growing complexity and heterogeneity of cancer types (Bertolini et al., 2015).

Drug repurposing leverages the existing knowledge and approval status of drugs, potentially reducing the time and cost associated with drug development (Ashburn & Thor, 2004). This is particularly pertinent in oncology, where the rapid progression of certain cancers demands swift therapeutic interventions. Furthermore, the repurposing of drugs often reveals unexpected benefits, such as lower toxicity profiles compared to traditional chemotherapy agents (Sharma et al., 2017).

An illustrative example of successful drug repurposing in oncology is the reassignment of Thalidomide, initially marketed as a sedative, for the treatment of multiple myeloma, significantly improving patient outcomes (Palumbo et al., 2008). This has paved the way for a broader investigation into existing drugs, opening new frontiers in the fight against cancer.

The following sections will explore deeper into various case studies of drug repurposing in cancer treatment, highlighting the scientific rationale, clinical outcomes, and future potential of this promising approach.

Challenges and Limitations: Navigating the Hurdles in Drug Repurposing for Cancer

While drug repurposing in oncology presents a promising avenue, it is not without its challenges and limitations. This section critically examines the hurdles faced in this domain, ranging from regulatory issues to scientific barriers. A key challenge lies in the repositioning of drugs for off-label use in cancer, which often encounters regulatory and patent-related obstacles (Nosengo, 2016). Moreover, the complexity of cancer biology itself poses significant challenges. The heterogeneity of tumor types and the evolution of drug resistance mechanisms demand a nuanced understanding of the molecular and cellular contexts in which these drugs operate (Vasan, Baselga & Hyman, 2019).

Furthermore, despite the reduced cost and time benefits, the financial incentives for pharmaceutical companies to invest in repurposing non-patentable or generic drugs for cancer are often limited, leading to a gap in research and development (Pushpakom et al., 2019). This section will delve into these challenges in detail, supported by specific examples and case studies, to provide a realistic perspective on the roadblocks and potential solutions in the field of drug repurposing for cancer treatment.

Metformin – From Diabetes to Cancer Therapeutics

Metformin, a widely used medication for type 2 diabetes, has emerged as a promising candidate in the oncology field. This section will delve into a comprehensive case study of Metformin, exploring its journey from a diabetic treatment to a potential anti-cancer drug.

Emerging evidence suggests that Metformin exerts anti-cancer effects through the activation of AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, which leads to the inhibition of cancer cell growth and proliferation (Zakikhani et al., 2006). Clinical studies have shown a significant reduction in cancer incidence among diabetic patients treated with Metformin (Evans et al., 2005). Further, observational studies have indicated its potential efficacy in reducing cancer mortality (Currie et al., 2009).

This case study will provide an in-depth analysis of the clinical trials, molecular mechanisms, and patient outcomes associated with Metformin’s repurposing in cancer treatment, discussing its therapeutic potential and the insights it offers into the broader field of drug repurposing.

Thalidomide – A Remarkable Transformation in Multiple Myeloma Treatment

Thalidomide, initially developed as a sedative and infamously known for causing birth defects, has undergone a dramatic transformation in its medical application, now playing a pivotal role in treating multiple myeloma, a type of blood cancer. This case study will explore the journey of Thalidomide from a pharmaceutical pariah to a cornerstone in multiple myeloma therapy.

The rediscovery of Thalidomide’s anti-angiogenic and immunomodulatory properties led to its repurposing in oncology, particularly for multiple myeloma (Singhal et al., 1999). Clinical trials have demonstrated its effectiveness in combination with other drugs, leading to improved survival rates and progression-free survival in patients (Palumbo et al., 2008).

This section will analyze the clinical trials, the biological mechanisms behind Thalidomide’s efficacy in multiple myeloma, and its impact on treatment protocols. Additionally, it will discuss the risk management strategies developed to mitigate its teratogenic effects, showcasing how a drug’s historical drawbacks can be addressed and repurposed for beneficial outcomes.

Aspirin – A Potential Ally in Colorectal Cancer Prevention and Treatment

Aspirin, a common non-steroidal anti-inflammatory drug (NSAID) known for its pain-relieving and anti-inflammatory properties, has garnered significant attention for its potential role in preventing and treating colorectal cancer. This case study explores the journey of Aspirin from a basic over-the-counter medication to a potential therapeutic agent in oncology.

Extensive epidemiological studies have suggested that regular Aspirin use is associated with a reduced risk of colorectal cancer (Rothwell et al., 2010). The proposed mechanism involves Aspirin’s ability to inhibit cyclooxygenase enzymes, leading to a decrease in prostaglandin production, which is implicated in tumorigenesis (Drew et al., 2016). Furthermore, clinical trials have indicated that Aspirin can improve survival in patients with colorectal cancer, particularly in those with tumors expressing high levels of COX-2 (Chan et al., 2012).

This section will delve into the research findings, clinical trials, and the evolving understanding of Aspirin’s role in colorectal cancer, encompassing both its preventative potential and therapeutic efficacy. The study will also address the challenges in Aspirin’s repurposing, such as determining optimal dosing and understanding the risks associated with long-term use.

Disulfiram – Repurposing an Anti-Alcoholism Drug for Cancer Treatment

Disulfiram, traditionally used in the treatment of chronic alcoholism, has shown potential as an anti-cancer agent, presenting an intriguing case of drug repurposing. This case study examines the transition of Disulfiram from an alcohol deterrent to a promising candidate in cancer therapy.

Research has uncovered that Disulfiram, especially when combined with copper, exhibits cytotoxic effects on cancer cells. The proposed mechanism involves the induction of reactive oxygen species and the inhibition of proteasome and NF-κB activities, leading to cancer cell death (Skrott et al., 2017). Clinical studies have begun to explore its efficacy in treating various types of cancers, including breast and prostate cancer, with some promising results (Cvek & Dvorak, 2008).

This section will provide a detailed analysis of the scientific evidence supporting Disulfiram’s anti-cancer properties, the outcomes of clinical trials, and the potential implications of these findings for future cancer treatments. It will also discuss the challenges and considerations in integrating Disulfiram into standard cancer therapy protocols.

Ivermectin – An Antiparasitic Agent’s Potential in Leukemia Treatment

Ivermectin, a drug commonly used for treating parasitic infections, has recently gained attention for its potential application in treating certain types of leukemia. This case study focuses on the exploration of Ivermectin as an oncological treatment, highlighting its journey from an antiparasitic agent to a potential cancer therapeutic.

Research has indicated that Ivermectin can induce apoptosis in leukemia cells by inhibiting the WNT signaling pathway, which is often dysregulated in various types of cancers (Wang et al., 2016). Additionally, studies have shown that Ivermectin can enhance the efficacy of existing chemotherapy drugs, suggesting its use as a combination therapy in leukemia treatment (Dou et al., 2016).

This section will delve into the biological mechanisms underlying Ivermectin’s anti-cancer effects, review the outcomes from clinical trials, and discuss its potential role in leukemia therapy. It will also address the challenges in repurposing Ivermectin for cancer treatment, including dosage optimization and understanding its side effect profile in the oncological context.

Sildenafil – Beyond Erectile Dysfunction to Targeting Cancer

Sildenafil, widely known for treating erectile dysfunction, has shown unexpected potential in cancer therapy. This case study examines the repurposing of Sildenafil, originally developed for cardiovascular conditions and later popularized for erectile dysfunction, as a novel approach in cancer treatment.

Emerging research indicates that Sildenafil may have therapeutic benefits in cancer treatment due to its ability to enhance the effects of chemotherapeutic agents. The drug is believed to work by inhibiting the PDE5 enzyme, leading to increased cyclic GMP levels, which can have anti-tumor effects (Das et al., 2015). Studies have also shown that Sildenafil can improve the efficacy of doxorubicin in the treatment of prostate cancer, while reducing its cardiotoxicity, offering a dual benefit (Zhang et al., 2015).

This section explores the scientific basis for Sildenafil’s application in oncology, including its molecular mechanisms and the results of clinical trials. It also discusses the challenges and future prospects of integrating Sildenafil into cancer therapy protocols, considering its well-established safety profile and potential synergistic effects with existing cancer treatments.

Propranolol – From Managing Heart Conditions to Inhibiting Tumor Growth

Propranolol, a beta-blocker traditionally used for treating heart conditions like hypertension and arrhythmias, has recently been explored for its potential in cancer treatment, particularly in reducing tumor growth and metastasis. This case study delves into the repurposing of Propranolol as an oncological therapy.

The anti-cancer potential of Propranolol has been attributed to its ability to inhibit adrenergic signaling, which can influence tumor cell proliferation and angiogenesis. Studies have shown that Propranolol can reduce the progression and improve the survival rates in patients with different types of cancer, such as breast cancer and melanoma (Barron et al., 2016). Clinical trials have also suggested that Propranolol, when used in combination with other treatments, can enhance therapeutic outcomes and reduce metastatic spread (Pasquier et al., 2011).

In this section, the focus will be on the molecular mechanisms of Propranolol’s action against cancer cells, the outcomes of clinical studies, and its potential as a complement to standard cancer therapies. The challenges and future directions for integrating Propranolol into oncological treatment regimens will also be discussed, considering its well-known safety profile and pharmacological effects.

Celecoxib – A Pain Reliever’s Role in Cancer Therapy

Celecoxib, primarily known as a nonsteroidal anti-inflammatory drug (NSAID) used for pain relief in conditions like arthritis, has been identified for its potential in cancer therapy. This case study explores the transition of Celecoxib from a pain management medication to a promising adjunct in cancer treatment.

The anti-cancer properties of Celecoxib are primarily attributed to its ability to inhibit cyclooxygenase-2 (COX-2), an enzyme that plays a significant role in the inflammatory process and is often overexpressed in various cancers. Studies have demonstrated that Celecoxib can suppress tumor growth and reduce the risk of cancer recurrence, particularly in colorectal cancer (Harris et al., 2003). Furthermore, Celecoxib has been investigated for its synergistic effects with chemotherapy and radiation therapy, showing potential to enhance the efficacy of traditional cancer treatments (Steinbach et al., 2000).

This section will discuss the molecular basis of Celecoxib’s action in cancer, review findings from clinical trials, and consider the implications of these findings for future cancer treatment strategies. Additionally, the challenges in integrating Celecoxib into oncological treatment, including concerns about cardiovascular risks associated with its long-term use, will be examined.

Digoxin – A Cardiac Glycoside’s Role in Cancer Inhibition

Digoxin, a cardiac glycoside traditionally used to treat heart conditions such as atrial fibrillation and heart failure, has recently been investigated for its potential in cancer inhibition. This case study delves into the emerging role of Digoxin as an anti-cancer agent.

Emerging research has indicated that Digoxin possesses anti-neoplastic properties, potentially through its ability to inhibit the HIF-1alpha pathway, which is often upregulated in cancer cells, promoting tumor growth and metastasis (Zhang et al., 2012). Clinical observations have suggested a lower incidence of various cancers in patients receiving Digoxin for cardiac conditions (Biggar et al., 2012). Moreover, its potential synergy with chemotherapeutic drugs opens new avenues for combination therapies in cancer treatment.

This section will explore the molecular mechanisms behind Digoxin’s anti-cancer effects, the outcomes of clinical studies, and the potential implications of these findings for future cancer treatments. The challenges in incorporating Digoxin into oncological treatment, such as its narrow therapeutic index and potential toxicity, will also be discussed, emphasizing the need for careful dosage management and patient monitoring.

Bupropion – An Antidepressant’s Potential in Lung Cancer Management

Bupropion, primarily known as an antidepressant and smoking cessation aid, has recently been identified for its potential in lung cancer treatment. This case study focuses on the exploration of Bupropion as an unconventional but promising therapeutic option in the realm of oncology.

Research has suggested that Bupropion may exert anti-cancer effects due to its ability to inhibit the proliferation of lung cancer cells. Studies indicate that Bupropion, through its action as a norepinephrine-dopamine reuptake inhibitor, can induce apoptosis in non-small cell lung cancer cells (NSCLC) and may enhance the sensitivity of these cells to traditional chemotherapy (Sung et al., 2011). Additionally, its role in aiding smoking cessation indirectly contributes to lung cancer prevention.

This section will delve into the pharmacological actions of Bupropion in the context of lung cancer, discussing findings from preclinical studies and the implications for future clinical trials. The challenges in repurposing Bupropion for lung cancer, such as determining optimal dosing and understanding potential interactions with existing cancer therapies, will also be examined.

Statins – Cholesterol-Lowering Agents as Potential Anticancer Therapeutics

Statins, widely prescribed for lowering cholesterol, have recently garnered attention for their potential anticancer properties. This case study explores the repurposing of statins, typically used to prevent cardiovascular diseases, in the context of cancer treatment.

Research has shown that statins may have a protective effect against various types of cancer, including breast, prostate, and colorectal cancers. The proposed mechanism involves the inhibition of the mevalonate pathway, which is crucial for the proliferation and survival of cancer cells (Gazzerro et al., 2012). Clinical studies have also suggested that statins can synergize with chemotherapy, potentially enhancing its efficacy and reducing drug resistance (Cardwell et al., 2014).

This section will examine the biological basis for statins’ anticancer effects, review the outcomes of relevant clinical trials, and discuss the potential of these widely used drugs in the oncology setting. Challenges such as the need for precise dosing, understanding potential side effects in cancer patients, and the variation in response among different statins will also be addressed.

Verapamil – A Cardiovascular Drug’s Emerging Role in Cancer Therapy

Verapamil, a calcium channel blocker traditionally used in the treatment of hypertension and cardiac arrhythmias, is being investigated for its potential role in cancer therapy. This case study examines the repurposing of Verapamil, exploring its emerging application in the oncological landscape.

The interest in Verapamil as a cancer therapy option is based on its ability to modulate multidrug resistance (MDR) in cancer cells. Verapamil has been shown to inhibit P-glycoprotein, a protein that often contributes to the resistance of cancer cells to chemotherapy drugs (Solomon et al., 1991). This inhibition enhances the effectiveness of chemotherapy agents by preventing the efflux of these drugs from cancer cells, thereby increasing their intracellular concentrations (Sharma et al., 1993).

This section will delve into the pharmacodynamics of Verapamil in the context of cancer treatment, examining its potential to overcome drug resistance, a significant hurdle in effective cancer therapy. The findings from clinical trials and preclinical studies will be reviewed, and the challenges in incorporating Verapamil into cancer treatment regimens, such as potential cardiac side effects, will be discussed.

Tamoxifen – Repurposing a Hormone Therapy Drug for Glioblastoma Treatment

Tamoxifen, well-known for its use in hormone receptor-positive breast cancer treatment, has been identified for its potential therapeutic role in treating glioblastoma, an aggressive type of brain cancer. This case study focuses on the exploration of Tamoxifen as an innovative approach in glioblastoma therapy.

Research has suggested that Tamoxifen may exert anti-tumor effects in glioblastoma through multiple mechanisms. These include the inhibition of protein kinase C (PKC) and the modulation of estrogen receptor pathways, which are implicated in the growth and proliferation of glioblastoma cells (Couldwell et al., 1994). Additionally, Tamoxifen has been observed to enhance the efficacy of traditional chemotherapeutic agents and improve the penetration of these drugs across the blood-brain barrier (Boado et al., 1994).

This section will explore the scientific rationale for repurposing Tamoxifen in glioblastoma treatment, review the outcomes from clinical studies, and discuss the potential challenges and implications of these findings for future cancer treatments. The unique pharmacological properties of Tamoxifen, including its ability to cross the blood-brain barrier, make it a particularly intriguing candidate for brain cancer therapy.

DISCUSSION

The exploration of drug repurposing in oncology, as exemplified by the diverse case studies, highlights a promising and innovative approach in cancer treatment. This discussion aims to synthesize the insights gleaned from these case studies and consider their broader implications in the field of oncology.

Integrating Repurposed Drugs into Cancer Therapy

One significant insight is the potential for repurposed drugs to complement existing cancer treatments. Drugs like Metformin, Thalidomide, and Celecoxib demonstrate how agents with well-established safety profiles can be integrated into cancer therapy, potentially enhancing efficacy and reducing adverse effects. However, this integration requires careful consideration of dosing, scheduling, and patient selection, as seen in the case of Disulfiram and Sildenafil.

Challenges and Future Directions

Despite promising results, challenges remain. These include regulatory hurdles, the need for more robust clinical trials, and understanding the long-term impacts of these drugs in oncology settings. For example, the cardiovascular risks associated with Celecoxib and the teratogenic effects of Thalidomide necessitate rigorous monitoring and risk management strategies.

Potential for Personalized Medicine

The diversity in mechanisms of action, as seen in the inhibition of WNT signaling by Ivermectin and the anti-angiogenic effects of Propranolol, opens avenues for personalized medicine. This approach could tailor treatments based on individual genetic profiles and tumor characteristics, maximizing efficacy and minimizing side effects.

Economic and Ethical Considerations

Drug repurposing can also be economically advantageous, offering cost-effective alternatives to expensive cancer drugs. Yet, this raises ethical considerations regarding the incentives for pharmaceutical companies to invest in repurposing non-patentable drugs.

Conclusion

In conclusion, drug repurposing in oncology presents a frontier rich with opportunities and challenges. While the journey from bench to bedside is complex, the potential benefits for cancer patients worldwide are immense. Future research should focus on comprehensive clinical trials, understanding the molecular mechanisms of these drugs in cancer, and developing strategies to seamlessly integrate them into standard care practices.

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