Drug Repurposing in Human Cancers

2020 ◽  
Vol 27 (42) ◽  
pp. 7213-7213
Author(s):  
Gabriele Grassi ◽  
Mario Grassi
Keyword(s):  
Drug Repurposing ◽  
Human Cancers

scholarly journals Identification of important genes and drug repurposing based on clinical-centered analysis across human cancers

2020 ◽  
Author(s):  
Ying Li ◽  
Ya-ping Dong ◽  
You-wen Qian ◽  
Le-xing Yu ◽  
Wen Wen ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Human Cancers

scholarly journals The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy - Drug Repurposing

2020 ◽  
Author(s):  
Joanna E Zawacka-Pankau
Keyword(s):  
Cancer Therapy ◽  
P53 Protein ◽  
Drug Repurposing ◽  
Standard Of Care ◽  
Tp53 Gene ◽  
Current Standard ◽  
Li Fraumeni Syndrome ◽  
Inherited Cancer ◽  
Human Cancers ◽  
New Treatments

p53 and p73 are critical tumor suppressors often inactivated in human cancers through various mechanisms. Owing to high structural homology, the proteins have many common functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the ‘guardian of the genome’ and together with p73 form a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni Syndrome (LFS), the inherited cancer predisposition. In cancers where TP53 gene is intact, p53 is degraded. Despite the ongoing efforts, the treatment of cancers remains challenging. This is due to late diagnoses, the toxicity of current standard of care and marginal benefit of newly approved therapies. Presently, the endeavours focus on reactivating p53 exclusively, neglecting the potential of the restoration of p73 protein for cancer eradication. Taken that several small molecules reactivating p53 failed in clinical trials, there is a need to develop new treatments targeting p53 proteins in cancer. This review outlines the most advanced strategies to reactivate p53 and p73 and describes drug repurposing approaches for the efficient reinstatement of the p53 proteins for cancer therapy.

scholarly journals The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy - Drug Repurposing

2020 ◽  
Author(s):  
Joanna E Zawacka-Pankau
Keyword(s):  
Cancer Therapy ◽  
P53 Protein ◽  
Drug Repurposing ◽  
Protein Family ◽  
Mutant P53 ◽  
Li Fraumeni Syndrome ◽  
Inherited Cancer ◽  
Human Cancers ◽  
New Treatments ◽  
Cycle Regulation

p53 and p73 are critical tumor suppressors inactivated in human cancers through various mechanisms. Owing to high structural homology, the proteins share many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the ‘guardian of the genome’ and forms a critical barrier against cancer development and progression. It is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li-Fraumeni Syndrome (LFS), the inherited cancer predisposition. Despite the ongoing effort, the treatment of cancers harbouring mutant p53 still remains challenging due to late diagnoses and the treatment-related toxicity and marginal benefit upon approval of new therapies. Presently, the efforts focus on activating p53 exclusively, neglecting the potential of the restoration of the p73 protein in tumors. Taken that several small molecules activating wild-type p53 have failed in clinical trials, and mutant p53 reactivating drugs have not been approved yet, there is a pressing need to develop new treatments activating p53 proteins. This review outlines the still despised therapeutic avenue, drug repurposing, which brings hope for the efficient reinstatement of the p53 protein family for improved cancer therapy.

scholarly journals The Undervalued Avenue to Reinstate Tumor Suppressor Functionality of the p53 Protein Family for Improved Cancer Therapy-Drug Repurposing

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2717
Author(s):  
Joanna E. Zawacka-Pankau
Keyword(s):  
Cancer Therapy ◽  
P53 Protein ◽  
Drug Repurposing ◽  
Standard Of Care ◽  
Tp53 Gene ◽  
Current Standard ◽  
Li Fraumeni Syndrome ◽  
Inherited Cancer ◽  
Human Cancers ◽  
New Treatments

p53 and p73 are critical tumor suppressors that are often inactivated in human cancers through various mechanisms. Owing to their high structural homology, the proteins have many joined functions and recognize the same set of genes involved in apoptosis and cell cycle regulation. p53 is known as the ‘guardian of the genome’ and together with p73 forms a barrier against cancer development and progression. The TP53 is mutated in more than 50% of all human cancers and the germline mutations in TP53 predispose to the early onset of multiple tumors in Li–Fraumeni syndrome (LFS), the inherited cancer predisposition. In cancers where TP53 gene is intact, p53 is degraded. Despite the ongoing efforts, the treatment of cancers remains challenging. This is due to late diagnoses, the toxicity of the current standard of care and marginal benefit of newly approved therapies. Presently, the endeavors focus on reactivating p53 exclusively, neglecting the potential of the restoration of p73 protein for cancer eradication. Taken that several small molecules reactivating p53 failed in clinical trials, there is a need to develop new treatments targeting p53 proteins in cancer. This review outlines the most advanced strategies to reactivate p53 and p73 and describes drug repurposing approaches for the efficient reinstatement of the p53 proteins for cancer therapy.

THE ROLE OF TGFΒ IN HUMAN CANCERS

Pathology ◽  
2001 ◽  
Vol 33 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Shew-Fung Wong, Leslie C. Lai
Keyword(s):  
Human Cancers

Specific inhbitor of ERK 1/2 AEZS-131: anticancer activity in models of human cancers with and without overactivation of ERK 1/2

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
JB Engel ◽  
S Meyer ◽  
J Dietl ◽  
B Kwok ◽  
O Ortmann ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Human Cancers

Drug Repurposing Studies Targeting SARS-nCoV2: An Ensemble Docking Approach on Drug Target 3C-like Protease (3CLpro)

2020 ◽  
Author(s):  
Shruti Koulgi ◽  
Vinod Jani ◽  
Mallikarjunachari Uppuladinne ◽  
Uddhavesh Sonavane ◽  
Asheet Kumar Nath ◽  
...  
Keyword(s):  
Drug Repurposing ◽  
Drug Binding ◽  
Ensemble Docking ◽  
Drug Molecules ◽  
Drug Binding Site ◽  
Main Protease ◽  
Docking Approach ◽  
Novel Coronavirus ◽  
Markov State Modeling ◽  
Viral Polyprotein

<p>The COVID-19 pandemic has been responsible for several deaths worldwide. The causative agent behind this disease is the Severe Acute Respiratory Syndrome – novel Coronavirus 2 (SARS-nCoV2). SARS-nCoV2 belongs to the category of RNA viruses. The main protease, responsible for the cleavage of the viral polyprotein is considered as one of the hot targets for treating COVID-19. Earlier reports suggest the use of HIV anti-viral drugs for targeting the main protease of SARS-CoV, which caused SARS in the year 2002-03. Hence, drug repurposing approach may prove to be useful in targeting the main protease of SARS-nCoV2. The high-resolution crystal structure of 3CL<sup>pro</sup> (main protease) of SARS-nCoV2 (PDB ID: 6LU7) was used as the target. The Food and Drug Administration (FDA) approved and SWEETLEAD database of drug molecules were screened. The apo form of the main protease was simulated for a cumulative of 150 ns and 10 μs open source simulation data was used, to obtain conformations for ensemble docking. The representative structures for docking were selected using RMSD-based clustering and Markov State Modeling analysis. This ensemble docking approach for main protease helped in exploring the conformational variation in the drug binding site of the main protease leading to efficient binding of more relevant drug molecules. The drugs obtained as best hits from the ensemble docking possessed anti-bacterial and anti-viral properties. Small molecules with these properties may prove to be useful to treat symptoms exhibited in COVID-19. This <i>in-silico</i> ensemble docking approach would support identification of potential candidates for repurposing against COVID-19.</p>

Sitagliptin: a potential drug for the treatment of SARS-CoV-2?

2020 ◽  
Author(s):  
Sanaa Bardaweel
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Antimalarial Drug ◽  
Drug Repurposing ◽  
Spike Protein ◽  
Diabetic Patients ◽  
Potential Drug ◽  
Chemokine Production ◽  
Drug Discovery And Development ◽  
Sequence Identity

Recently, an outbreak of fatal coronavirus, SARS-CoV-2, has emerged from China and is rapidly spreading worldwide. As the coronavirus pandemic rages, drug discovery and development become even more challenging. Drug repurposing of the antimalarial drug chloroquine and its hydroxylated form had demonstrated apparent effectiveness in the treatment of COVID-19 associated pneumonia in clinical trials. SARS-CoV-2 spike protein shares 31.9% sequence identity with the spike protein presents in the Middle East Respiratory Syndrome Corona Virus (MERS-CoV), which infects cells through the interaction of its spike protein with the DPP4 receptor found on macrophages. Sitagliptin, a DPP4 inhibitor, that is known for its antidiabetic, immunoregulatory, anti-inflammatory, and beneficial cardiometabolic effects has been shown to reverse macrophage responses in MERS-CoV infection and reduce CXCL10 chemokine production in AIDS patients. We suggest that Sitagliptin may be beneficial alternative for the treatment of COVID-19 disease especially in diabetic patients and patients with preexisting cardiovascular conditions who are already at higher risk of COVID-19 infection.

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