**1.1 What are the problems?**

Cancer is the second deadliest disease after cardiovascular diseases, causing loss of billions of lives across the world. Although human kind has developed so many anti-cancer medicines, none of them are able to cure the disease. After spending of around \$650 million for the development in research and development of New Chemical Entity (NCE) during time periods of 12–17 years, successful outcome compared to standard drugs is less [1]. The success ratio for this NCE in clinical trial is less than 10%. Many times, the effects on outcomes like disease free survival, quality of life treatment related side effects and complications are discouraging. According to ESMO 2019 press release, there was no link between drug cost and clinical benefit measured by ESMO-MCBS and the American Society of Clinical Oncology Value Framework (ASCO-VF) for various drugs approved for adult solid tumor in four European countries and the USA from 2009 to 2017. So, it would

add extra treatment cost to patient therapy. According to Prof. Kerstin Vokinger, University of Zurich, Switzerland, and affiliated with the Program on Regulation, Therapeutics, and Law (Harvard Medical School, USA), drug pricing should be aligned with clinical value [2]. There was drastic decline in average number of FDA approved drug since the 1990, but the number of cancer cases rising every year for each cancer. So, this imbalance of demand and supply of effective anti-cancer drugs can be balanced by implication of drug repurposing [3]. In the oncology medicine, the US FDA approved 4 new drugs in 2016 while it was 14 drugs in 2015 and 9 drugs in 2014 and 2013 that indicate decrease in anti-cancer drug discovery [4].

### **1.2 How repurposing can help?**

To overcome the problems linked to high expenditures, lengthy and tedious research for every NCE with low success in clinical trial, repurposing can help where scientists are trying to investigate new therapeutic indication for existing approved drugs. Drug repurposing has many advantages in terms of efficient utilization of time and money for drug discovery and development processes. The proposed medicines for repurposing already have approved pharmaceutical data related to its formulation, Pharmacokinetic (absorption, distribution, metabolism and excretion) and pharmacodynamic profile that collected during preclinical and clinical trial. The proposed medicine also passed through much toxicity, side effects testing and passed the phase 4 of post marketing surveillance so the safety is already established and that reduce the chances of drug failure at the end screening process of drug discovery [5]. The repurposing can drastically reduce drug discovery time line from 12–17 years to 3–12 years due to availability of drug's pharmacology and pharmaceuticals data [6]. The concept of Drug Repurposing is based on validating and application of previously approved drug by FDA in the treatment of another disease that might be relevant or irrelevant to existing use in disease. The principle of polypharmacology and pleiotropy was working behind drug repurposing. The anti-cancer drugs receive FDA approval are very costliest in recent years that significantly affect pharmacoeconomics of patients. For consideration, the cost for a combination-targeted therapy of monoclonal antibodies ipilimumab and nivolumab in treatment of metastatic melanoma has been estimated to per responder is around \$400,000 US [7, 8]. So, all these problems can be targeted by drug repurposing where it improves the chances of success, shortens the testing time, and reduces the huge investment in cancer drug design and development.

**123**

**Figure 2.**

**of attractive candidates**

*Various approaches of drug repurposing.*

*Drug Repurposing in Oncotherapeutics DOI: http://dx.doi.org/10.5772/intechopen.92302*

**2. Drug repositioning strategy**

**and development**

**1.3 Opportunities for drug repositioning comes from path of drug discovery** 

The process of new drug designing and development involve many steps as mentioned in **Figure 1**. It may happen that Drug is serendipitously screened and found positive result for another disease. Gills et al. tested few anti-HIV drugs against many cancer cell lines using cytotoxicity assays. He found that nelfinavir has potent broad-spectrum antitumor activity [9]. Repurposing can also possible if new role discovered for an existing target. In case of metformin, the similar pathway of is found to be important in two different diseases like diabetes and cancer. It has been observed that unexpected side effects found during and after clinical trials

During preliminary screening on Drug, many possibilities of drug repurposing may arise by chance and later based on proper justification few of them have been tested for alternate application in another disease that called as shifting from bench to bedside. Oppositely, it may happen that unpredicted results of clinical trials suggest ideas for drug repurposing and later same things justified by scientific experiments that called as bedside to bench. According to FDA approved drug database, around 80–90% of drug gets failed in clinical trials due to various reasons and one of the majors is that the lack of efficacy during phase- III of clinical trial. That failure rate figures out around 30–50% and all these drugs might be good candidate for repurposing. The **Figure 2** indicate different approaches that begin with constructing hypothesis based on existing fund of knowledge to expanding its *in silico* frame work for preliminary testing and later on validating facts based on more vigorous

**3. Necessity for drug repurposing in cancer treatment and availability** 

Comparing cancer with other disease that takes much time to develop and working insidiously. Every cancer begins with few mutations that suppress tumor suppression gene and promoting oncogene that leads to abnormal cell proliferation, escape of apoptosis, immune evasion, inflammation, defects in DNA damage repair mechanism,

show lead for drug repurposing like thalidomide for certain cancer.

and stringent analysis like preclinical and clinical studies [10].

#### **Figure 1.**

*Drug discovery and development with potential windows for drug repurposing.*

*Drug Repurposing - Hypothesis, Molecular Aspects and Therapeutic Applications*

add extra treatment cost to patient therapy. According to Prof. Kerstin Vokinger, University of Zurich, Switzerland, and affiliated with the Program on Regulation, Therapeutics, and Law (Harvard Medical School, USA), drug pricing should be aligned with clinical value [2]. There was drastic decline in average number of FDA approved drug since the 1990, but the number of cancer cases rising every year for each cancer. So, this imbalance of demand and supply of effective anti-cancer drugs can be balanced by implication of drug repurposing [3]. In the oncology medicine, the US FDA approved 4 new drugs in 2016 while it was 14 drugs in 2015 and 9 drugs

in 2014 and 2013 that indicate decrease in anti-cancer drug discovery [4].

To overcome the problems linked to high expenditures, lengthy and tedious research for every NCE with low success in clinical trial, repurposing can help where scientists are trying to investigate new therapeutic indication for existing approved drugs. Drug repurposing has many advantages in terms of efficient utilization of time and money for drug discovery and development processes. The proposed medicines for repurposing already have approved pharmaceutical data related to its formulation, Pharmacokinetic (absorption, distribution, metabolism and excretion) and pharmacodynamic profile that collected during preclinical and clinical trial. The proposed medicine also passed through much toxicity, side effects testing and passed the phase 4 of post marketing surveillance so the safety is already established and that reduce the chances of drug failure at the end screening process of drug discovery [5]. The repurposing can drastically reduce drug discovery time line from 12–17 years to 3–12 years due to availability of drug's pharmacology and pharmaceuticals data [6]. The concept of Drug Repurposing is based on validating and application of previously approved drug by FDA in the treatment of another disease that might be relevant or irrelevant to existing use in disease. The principle of polypharmacology and pleiotropy was working behind drug repurposing. The anti-cancer drugs receive FDA approval are very costliest in recent years that significantly affect pharmacoeconomics of patients. For consideration, the cost for a combination-targeted therapy of monoclonal antibodies ipilimumab and nivolumab in treatment of metastatic melanoma has been estimated to per responder is around \$400,000 US [7, 8]. So, all these problems can be targeted by drug repurposing where it improves the chances of success, shortens the testing time, and reduces the huge investment in cancer drug design and development.

**1.2 How repurposing can help?**

**122**

**Figure 1.**

*Drug discovery and development with potential windows for drug repurposing.*
