New drugs are not enough‑drug repositioning in oncology: An update

Armando, Romina; Gómez, Diego Luis Mengual; Gómez, Daniel E.

doi:10.3892/ijo.2020.4966

Cited by 61 publications

(65 citation statements)

References 529 publications

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“…Here, we propose an alternative approach based on the use of non-oncological drugs for OC treatment. This concept, called drug repurposing, is based on the knowledge of pharmacokinetics, pharmacodynamics, target identification, bioavailability, toxicity profiles, recommended dosage schemes, and consistent recognition of adverse effects, meaning that oncological indication development can begin at phase II of the clinical trials, making the research process less time-consuming and less expensive [ 17 , 18 , 19 , 20 ]. The incorporation of non-oncological drugs for cancer treatment is usually combined with chemotherapeutic agents, target therapies, or other repurposed drugs [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer

Nunes

Abreu

Bartosch

et al. 2020

IJMS

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The main challenge in ovarian cancer treatment is the management of recurrences. Facing this scenario, therapy selection is based on multiple factors to define the best treatment sequence. Target therapies, such as bevacizumab and polymerase (PARP) inhibitors, improved patient survival. However, despite their achievements, ovarian cancer survival remains poor; these therapeutic options are highly costly and can be associated with potential side effects. Recently, it has been shown that the combination of repurposed, conventional, chemotherapeutic drugs could be an alternative, presenting good patient outcomes with few side effects and low costs for healthcare institutions. The main aim of this review is to strengthen the importance of repurposed drugs as therapeutic alternatives, and to propose an in vitro model to assess the therapeutic value. Herein, we compiled the current knowledge on the most promising non-oncological drugs for ovarian cancer treatment, focusing on statins, metformin, bisphosphonates, ivermectin, itraconazole, and ritonavir. We discuss the primary drug use, anticancer mechanisms, and applicability in ovarian cancer. Finally, we propose the use of these therapies to perform drug efficacy tests in ovarian cancer ex vivo cultures. This personalized testing approach could be crucial to validate the existing evidences supporting the use of repurposed drugs for ovarian cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer

Nunes

Abreu

Bartosch

et al. 2020

IJMS

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“…The reason is probably that the optimal chemical structures are complex and difficult to synthesize, and are therefore associated with high research costs. The use of a simple scaf- fold is based on the low-risk approach and is very similar to the repurposing strategy (32). However, the present study has some limitations, considering the use of only one chemical repository.…”

Section: Discussionmentioning

confidence: 99%

Improving the odds of success in antitumoral drug development using scoring approaches towards heterocyclic scaffolds

et al. 2020

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One of the most commonly discussed topics in the field of drug discovery is the continuous search for anticancer therapies, in which small-molecule development plays an important role. Although a number of techniques have been established over the past decades, one of the main methods for drug discovery and development is still represented by rational, ligand-based drug design. However, the success rate of this method could be higher if not affected by cognitive bias, which renders many potential druggable scaffolds and structures overlooked. The present study aimed to counter this bias by presenting an objective overview of the most important heterocyclic structures in the development of anti-proliferative drugs. As such, the present study analyzed data for 91,438 compounds extracted from the Developmental Therapeutics Program (DTP) database provided by the National Cancer Institute. Growth inhibition data from these compounds tested on a panel of 60 cancer cell lines representing various tissue types (NCI-60 panel) was statistically interpreted using 6 generated scores assessing activity, selectivity, growth inhibition efficacy and potency of different structural scaffolds, Bemis-Murcko skeletons, chemical features and structures common among the analyzed compounds. Of the most commonly used rings, the most prominent anti-proliferative effects were produced by quinoline, tetrahydropyran, benzimidazole and pyrazole, while overall, the optimal results were produced by complex ring structures that originate from natural compounds. These results highlight the impact of certain ring structures on the anti-proliferative effects in drug design. In addition, considering that medicinal chemists usually focus their research on simpler scaffolds the majority of the time with no significant pay-off, the present study indicates several unused complex scaffolds that could be exploited when designing anticancer therapies for optimal results in the fight against cancer.

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“…The treatment schemes for xenotransplated mice with HCT116 are depicted in Figure 4A,B. Treatment began when xenotrasplants reached 50 mm 3 . The administration of AA at 250 mg/kg once weekly for three weeks reduced tumor growth in 49.19% ( Figure 5A).…”

Section: Aa Inhibited Tumor Growthmentioning

confidence: 99%

“…However, in the last two decades the overall survival rate has doubled, reaching an estimated median survival expectancy of 20 months. The latter is largely due to new therapeutic approaches that rely on the combined administration of novel molecular agents with well-known cytotoxic agents, or drug repositioning [3]. The former are modern agents first approved for medical use between the first decade of 2000 (e.g., bevacizumab, panitumumab, cetuximab, aflibercept, and regorafenib), whereas the second have a longer history of use (e.g., oxaliplatin, irinotecan, 5-fluorouracil, capecitabine), with only a few being more modern (e.g., trifluridine/tipiracil) [4,5].…”

Section: Introductionmentioning

confidence: 99%

A Higher Frequency Administration of the Nontoxic Cycloartane-Type Triterpene Argentatin A Improved Its Anti-Tumor Activity

et al. 2020

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Parthenium argentatum (Gray), commonly known as guayule, has been used to obtain natural rubber since the beginning of the 20th century. Additionally, the so called “resin” is a waste product derived from the industrial process. The cycloartane-type triterpene Argentatin A (AA) is one of the main constituents of the industrial waste resin. In this study we evaluated the AA anticancer activity both in vitro and in vivo in the HCT116 colon cancer cells. The apoptosis promotion of AA was assessed by the annexin V/propidium iodide (PI) assay. The senescence was evaluated for SA-β-galactosidase, and PCNA was used as a marker of proliferation. Its antitumor activity was evaluated using a xenograft mouse model. The results indicated that AA-induced apoptosis in HCT-116 cells and was positively stained for SA-β-galactosidase. In the xenografted mice test, the administration of AA at the dose of 250 mg/kg three times a week for 21 days reduced tumor growth by 78.1%. A comparable tumor reduction was achieved with cisplatin at the dose of 2 mg/kg administered three times a week for 21 days. However, nude mice treated with AA did not lose weight, as they did remarkably when treated with cisplatin. Furthermore, the animals treated with AA showed similar blood profiles as the healthy control group. These data indicate the low toxicity of AA compared to that shown by cisplatin.

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New drugs are not enough‑drug repositioning in oncology: An update

Cited by 61 publications

References 529 publications

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer

Recycling the Purpose of Old Drugs to Treat Ovarian Cancer

Improving the odds of success in antitumoral drug development using scoring approaches towards heterocyclic scaffolds

A Higher Frequency Administration of the Nontoxic Cycloartane-Type Triterpene Argentatin A Improved Its Anti-Tumor Activity

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