scholarly journals Pharmacogenomics, biomarker network and allele frequencies in colorectal cancer

2019 ◽  
Author(s):  
Andrés López-Cortés ◽  
César Paz-y-Miño ◽  
Santiago Guerrero ◽  
Gabriela Jaramillo-Koupermann ◽  
Dámaris P. Intriago-Baldeón ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Enzyme Activity ◽  
Precision Medicine ◽  
Drug Response ◽  
Therapeutic Strategy ◽  
Therapeutic Response ◽  
Cancer Death ◽  
Genomic Alterations ◽  
Comprehensive Review ◽  
Pharmacogenomics Biomarker

ABSTRACTColorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Over the last decades, several studies have shown that tumor-related genomic alterations predict tumor prognosis, drug response and toxicity. These observations have led to the development of a number of precision therapies based on individual genomic profiles. As part of these approaches, pharmacogenomics analyses genomic alterations that may predict an efficient therapeutic response. Studying these mutations as biomarkers for predicting drug response is of a great interest to improve precision medicine. Here we conduct a comprehensive review of the main pharmacogenomics biomarkers and genomic alterations affecting enzyme activity, transporter capacity, channels and receptors, and therefore the new advances in CRC precision medicine to select the best therapeutic strategy in populations worldwide, with a focus on Latin America.

scholarly journals A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer

2020 ◽  
Vol 19 (12) ◽  
pp. 2516-2527 ◽  
Author(s):  
Jason A. Somarelli ◽  
Roham Salman Roghani ◽  
Ali Sanjari Moghaddam ◽  
Beatrice C. Thomas ◽  
Gabrielle Rupprecht ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Discovery ◽  
Precision Medicine ◽  
Therapeutic Strategy ◽  
Discovery Pipeline ◽  
Novel Therapeutic

Towards Realizing the Vision of Precision Medicine: AI Based Prediction of Clinical Drug Response

2020 ◽  
Author(s):  
Johann de Jong ◽  
Ioana Cutcutache ◽  
Matthew Page ◽  
Sami Elmoufti ◽  
Cynthia Dilley ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Drug Response ◽  
Clinical Drug

scholarly journals Amorphous Ropinirole-Loaded Mucoadhesive Buccal Film: A Potential Patient-Friendly Tool to Improve Drug Pharmacokinetic Profile and Effectiveness

2020 ◽  
Vol 10 (4) ◽  
pp. 242
Author(s):  
Giulia Di Prima ◽  
Giuseppina Campisi ◽  
Viviana De Caro
Keyword(s):  
Buccal Mucosa ◽  
Therapeutic Strategy ◽  
Therapeutic Response ◽  
Ex Vivo ◽  
Hepatic Metabolism ◽  
Pharmacokinetic Profile ◽  
Promising Candidate ◽  
Steady State Condition ◽  
Drug Pharmacokinetic ◽  
Drug Flux

Nowadays the therapeutic strategies to manage Parkinson’s Disease are merely symptomatic and consist of administering L-DOPA and/or dopamine receptor agonists. Among these, Ropinirole (ROP) is a widely orally-administered molecule, although it is extensively susceptible to hepatic metabolism. Since literature reports the buccal mucosa as a potentially useful route to ROP administration, the development of novel, effective, and comfortable oromucosal formulations should prove desirable in order to both enhance the therapeutic efficacy of the drug and allow a personalized therapeutic strategy able to meet the patient’s needs. The results of the proposed ROP film as a new dosage form show that it is flexible; uniform; and characterized by suitable surface pH; good mucoadhesiveness; low swelling degree; and fast, complete drug release. Moreover, after ex vivo evaluation on a film having an area of 0.282 cm2 and dose of 2.29 mg, the results of drug flux through the buccal mucosa are closely comparable to the amount of ROP that reaches the bloodstream at the steady-state condition after ROP-PR 4 mg oral administration, calculated according to the literature (0.237 mg/cm2·h−1 vs. 0.243 mg/h, respectively). Moreover, drug flux and ROP dose could be accurately modulated time-by-time depending on the patient’s need, by varying the administered disk area. In addition, the proposed ROP film displays no lag time, producing an immediate drug input in the bloodstream, which could result in a prompt therapeutic response. These findings make ROP film a potentially comfortable and patient-friendly formulation, and a promising candidate for further clinical trials.

scholarly journals Gene Editing and Modulation: the Holy Grail for the Genetic Epilepsies?

2021 ◽  
Author(s):  
Jenna C. Carpenter ◽  
Gabriele Lignani
Keyword(s):  
Precision Medicine ◽  
Neurological Disorder ◽  
Gene Editing ◽  
Therapeutic Strategy ◽  
Therapeutic Potential ◽  
Single Gene ◽  
Drug Resistant ◽  
Holy Grail ◽  
Effective Therapeutic Strategy ◽  
Genetic Epilepsies

AbstractEpilepsy is a complex neurological disorder for which there are a large number of monogenic subtypes. Monogenic epilepsies are often severe and disabling, featuring drug-resistant seizures and significant developmental comorbidities. These disorders are potentially amenable to a precision medicine approach, of which genome editing using CRISPR/Cas represents the holy grail. Here we consider mutations in some of the most ‘common’ rare epilepsy genes and discuss the different CRISPR/Cas approaches that could be taken to cure these disorders. We consider scenarios where CRISPR-mediated gene modulation could serve as an effective therapeutic strategy and discuss whether a single gene corrective approach could hold therapeutic potential in the context of homeostatic compensation in the developing, highly dynamic brain. Despite an incomplete understanding of the mechanisms of the genetic epilepsies and current limitations of gene editing tools, CRISPR-mediated approaches have game-changing potential in the treatment of genetic epilepsy over the next decade.

scholarly journals Metformin and Niclosamide Synergistically Suppress Wnt and YAP in APC-Mutated Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3437
Author(s):  
Hee Eun Kang ◽  
Yoojeong Seo ◽  
Jun Seop Yun ◽  
Sang Hyun Song ◽  
Dawool Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Target Gene ◽  
Advanced Colorectal Cancer ◽  
Therapeutic Potential ◽  
Cancer Stemness ◽  
Reciprocal Regulation ◽  
Canonical Wnt

The Wnt and Hippo pathways are tightly coordinated and understanding their reciprocal regulation may provide a novel therapeutic strategy for cancer. Anti-helminthic niclosamide is an effective inhibitor of Wnt and is now in a phase II trial for advanced colorectal cancer (CRC) patients. We found that Axin2, an authentic target gene of canonical Wnt, acts as aYAP phosphorylation activator in APC-mutated CRC. While niclosamide effectively suppresses Wnt, it also inhibits Hippo, limiting its therapeutic potential for CRC. To overcome this limitation, we utilized metformin, a clinically available AMPK activator. This combinatory approach not only suppresses canonical Wnt activity, but also inhibits YAP activity in CRC cancer cells and in patient-derived cancer organoid through the suppression of cancer stemness. Further, combinatory oral administration suppressed in vivo tumorigenesis and the cancer progression of APC-MIN mice models. Our observations provide not only a reciprocal link between Wnt and Hippo, but also clinically available novel therapeutics that are able to target Wnt and YAP in APC-mutated CRC.

scholarly journals Combination of Cetuximab with Radioimmunotherapy Significantly Enhances Therapeutic Response in Colorectal Cancer

2014 ◽  
Vol 25 ◽  
pp. vi3
Author(s):  
V. Vassileva ◽  
M. Mazzantini ◽  
V. Rajkumar ◽  
M. Robson ◽  
A. Badar ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Response
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