Drug repurposing and relabeling for cancer therapy: Emerging benzimidazole antihelminthics with potent anticancer effects

One of the most lethal forms of CNS pathologies is glioblastoma multiforme (GBM) that represents high invasiveness, uncontrolled proliferation, and angiogenic features. Its invasiveness is responsible for the high recurrence even after maximal surgical interventions. Minocycline is a semisynthetic analog of tetracyclines with potential anti-inflammatory and anticancer effects, distinct from its antimicrobial activity. In this review, we highlight the importance and the cytotoxic mechanisms of minocycline on GBM pathophysiology. Considering the role of certain enzymes in autophagy, apoptosis, tumor cell invasion, and metastatic ability, the possible use of tetracyclines for cancer therapy should be investigated, especially GBM. The present study is, therefore, going to cover the main topics in minocycline pharmacology to date, encouraging its consideration as a new treatment approach for cancer and GBM.

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Doxazosin, a Classic Alpha 1-Adrenoceptor Antagonist, Overcomes Osimertinib Resistance in Cancer Cells via the Upregulation of Autophagy as Drug Repurposing

Biomedicines ◽

10.3390/biomedicines8080273 ◽

2020 ◽

Vol 8 (8) ◽

pp. 273 ◽

Cited By ~ 1

Author(s):

Shuhei Suzuki ◽

Masahiro Yamamoto ◽

Tomomi Sanomachi ◽

Keita Togashi ◽

Asuka Sugai ◽

...

Keyword(s):

Cancer Cells ◽

Safety Profile ◽

Kinase Inhibitor ◽

Drug Repositioning ◽

Growth Factor Receptor ◽

Drug Repurposing ◽

Adrenoceptor Antagonist ◽

Anticancer Effects ◽

Epidermal Growth ◽

Excellent Safety Profile

Osimertinib, which is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is an important anticancer drug because of its high efficacy and excellent safety profile. However, resistance against osimertinib is inevitable; therefore, therapeutic strategies to overcome the resistance are needed. Doxazosin, a classic quinazoline-based alpha 1-adrenoceptor antagonist is used to treat hypertension and benign prostatic hyperplasia with a known safety profile. The anticancer effects of doxazosin have been examined in various types of malignancies from the viewpoint of drug repositioning or repurposing. However, it currently remains unclear whether doxazosin sensitizes cancer cells to osimertinib. Herein, we demonstrated that doxazosin induced autophagy and enhanced the anticancer effects of osimertinib on the cancer cells and cancer stem cells of non-small cell lung cancer, pancreatic cancer, and glioblastoma at a concentration at which the growth of non-tumor cells was not affected. The osimertinib-sensitizing effects of doxazosin were suppressed by 3-methyladenine, an inhibitor of autophagy, which suggested that the effects of doxazosin were mediated by autophagy. The present study provides evidence for the efficacy of doxazosin as a combination therapy with osimertinib to overcome resistance against osimertinib.

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Computer-aided drug repurposing for cancer therapy: Approaches and opportunities to challenge anticancer targets

Seminars in Cancer Biology ◽

10.1016/j.semcancer.2019.09.023 ◽

2019 ◽

Cited By ~ 10

Author(s):

Carla Mottini ◽

Francesco Napolitano ◽

Zhongxiao Li ◽

Xin Gao ◽

Luca Cardone

Keyword(s):

Cancer Therapy ◽

Drug Repurposing ◽

Computer Aided

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A novel chemical inhibitor suppresses breast cancer cell growth and metastasis through inhibiting HPIP oncoprotein

Cell Death Discovery ◽

10.1038/s41420-021-00580-3 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Pengyun Li ◽

Shengjie Cao ◽

Yubing Huang ◽

Yanan Zhang ◽

Jie Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cell Growth ◽

Cancer Therapy ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Development ◽

Cancer Cell Growth ◽

Breast Cancer Cell Growth ◽

Anticancer Effects

AbstractIncreasing evidence suggests the pivotal role of hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) in cancer development and progression, indicating that HPIP inhibition may be a promising target for cancer therapy. Here, we screened compounds inhibiting breast cancer cell proliferation with HPIP fused with green fluorescent protein as a reporter. A novel agent named TXX-1-10 derived from rimonabant, an antagonist of cannabinoid receptor 1 with anticancer effects, has been discovered to reduce HPIP expression and has greater inhibitory effects on breast cancer cell growth and metastasis in vitro and in vivo than rimonabant. TXX-1-10 regulates HPIP downstream targets, including several important kinases involved in cancer development and progression (e.g., AKT, ERK1/2, and FAK) as well as cell cycle-, apoptosis-, migration-, and epithelial-to-mesenchymal transition (EMT)-related genes. Consistent with the results of anticancer effects, genome-wide RNA sequencing indicated that TXX-1-10 has more significant effects on regulation of the expression of genes related to DNA replication, cell cycle, apoptosis, cell adhesion, cell migration, and invasion than rimonabant. In addition, TXX-1-10 significantly regulated genes associated with the cell growth and extracellular matrix organization, many of which were shown to be regulated by HPIP. Moreover, compared with rimonabant, TXX-1-10 greatly reduces blood-brain barrier penetrability to avoid adverse central depressive effects. These findings suggest that HPIP inhibition may be a useful strategy for cancer treatment and TXX-1-10 is a promising candidate drug for cancer therapy.

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Repurposing of Metformin for Cancer Therapy: Updated Patent and Literature Review

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892816666210615163417 ◽

2021 ◽

Vol 16 ◽

Author(s):

Zainab Sabry Othman Ahmed ◽

Matthew Golovoy ◽

Yassen Abdullah ◽

Reda Saber Ibrahim Ahmed ◽

Q. Ping Dou

Keyword(s):

Clinical Trials ◽

Cancer Therapy ◽

Late Phase ◽

Drug Dosage ◽

Great Promise ◽

Cancer Therapies ◽

Anticancer Properties ◽

Anticancer Effects ◽

Pubmed Database ◽

Early Phase Clinical Trials

Background: Over recent years, there has been an increasing focus on the repurposing of existing, well-known medications for new, novel usage. One such drug is metformin, typically utilized in the management of diabetes, which demonstrates a positive relationship between its administration and lower cancer morbidity and mortality. Based on this finding, numerous studies and clinical trials have been conducted to examine the potential usage of metformin as an anticancer agent. Objective: This article aims to summarize metformin’s anticancer effects through reviewing its literature and patents, with a focus on its potential to be repurposed for cancer therapy. Methods: Various databases were examined using keywords, ‘Metformin’ and ‘Cancer’. Research articles were collected through the PubMed database, clinical trials were obtained from the Clinical Trials database, and patents were collected through the Google Patents database. Results: Metformin shows antineoplastic activity in various models. These anticancer properties appear to synergize with existing chemotherapeutics, which allows for a reduction in drug dosage without losing potency while minimizing adverse effects. Numerous patents on metformin have been filed which claim various combination therapies, delivery methods, and uses for cancer therapy, displaying an increasing interest in metformin’s anticancer potential. Conclusion: Preclinical studies, along with early phase clinical trials, have examined antitumor properties of metformin on a variety of cancers. Metformin’s anticancer effects are well documented, demonstrating a great promise in improving current cancer therapies. However, there is a significant lack of late phase clinical trials, specifically those involving non-diabetic cancer patients, and therefore further research in this area is required.

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