scholarly journals Extracting genetic alteration information for personalized cancer therapy from ClinicalTrials.gov

2016 ◽  
Vol 23 (4) ◽  
pp. 750-757 ◽  
Author(s):  
Jun Xu ◽  
Hee-Jin Lee ◽  
Jia Zeng ◽  
Yonghui Wu ◽  
Yaoyun Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Knowledge Base ◽  
Genetic Alterations ◽  
Genetic Alteration ◽  
Treatment Trials ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer ◽  
Manual Review

Abstract Objective: Clinical trials investigating drugs that target specific genetic alterations in tumors are important for promoting personalized cancer therapy. The goal of this project is to create a knowledge base of cancer treatment trials with annotations about genetic alterations from ClinicalTrials.gov. Methods: We developed a semi-automatic framework that combines advanced text-processing techniques with manual review to curate genetic alteration information in cancer trials. The framework consists of a document classification system to identify cancer treatment trials from ClinicalTrials.gov and an information extraction system to extract gene and alteration pairs from the Title and Eligibility Criteria sections of clinical trials. By applying the framework to trials at ClinicalTrials.gov, we created a knowledge base of cancer treatment trials with genetic alteration annotations. We then evaluated each component of the framework against manually reviewed sets of clinical trials and generated descriptive statistics of the knowledge base. Results and Discussion: The automated cancer treatment trial identification system achieved a high precision of 0.9944. Together with the manual review process, it identified 20 193 cancer treatment trials from ClinicalTrials.gov. The automated gene-alteration extraction system achieved a precision of 0.8300 and a recall of 0.6803. After validation by manual review, we generated a knowledge base of 2024 cancer trials that are labeled with specific genetic alteration information. Analysis of the knowledge base revealed the trend of increased use of targeted therapy for cancer, as well as top frequent gene-alteration pairs of interest. We expect this knowledge base to be a valuable resource for physicians and patients who are seeking information about personalized cancer therapy.

scholarly journals Targeting Akt in cancer for precision therapy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hui Hua ◽  
Hongying Zhang ◽  
Jingzhu Chen ◽  
Jiao Wang ◽  
Jieya Liu ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Protein Kinases ◽  
Anticancer Agents ◽  
Phase Iii ◽  
Akt Inhibitor ◽  
Precision Therapy ◽  
And Migration ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

AbstractBiomarkers-guided precision therapeutics has revolutionized the clinical development and administration of molecular-targeted anticancer agents. Tailored precision cancer therapy exhibits better response rate compared to unselective treatment. Protein kinases have critical roles in cell signaling, metabolism, proliferation, survival and migration. Aberrant activation of protein kinases is critical for tumor growth and progression. Hence, protein kinases are key targets for molecular targeted cancer therapy. The serine/threonine kinase Akt is frequently activated in various types of cancer. Activation of Akt promotes tumor progression and drug resistance. Since the first Akt inhibitor was reported in 2000, many Akt inhibitors have been developed and evaluated in either early or late stage of clinical trials, which take advantage of liquid biopsy and genomic or molecular profiling to realize personalized cancer therapy. Two inhibitors, capivasertib and ipatasertib, are being tested in phase III clinical trials for cancer therapy. Here, we highlight recent progress of Akt signaling pathway, review the up-to-date data from clinical studies of Akt inhibitors and discuss the potential biomarkers that may help personalized treatment of cancer with Akt inhibitors. In addition, we also discuss how Akt may confer the vulnerability of cancer cells to some kinds of anticancer agents.

Oncogenomics and CYP450 Implications in Personalized Cancer Therapy

2020 ◽  
Vol 17 (2) ◽  
pp. 104-113
Author(s):  
G.K. Udayaraja ◽  
I. Arnold Emerson
Keyword(s):  
Cytochrome P450 ◽  
Cancer Treatment ◽  
Cancer Susceptibility ◽  
Mutant Gene ◽  
Genome Project ◽  
Interdisciplinary Field ◽  
Precision Therapy ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer ◽  
Genetic Events

Background: The Human Genome Project has unleashed the power of genomics in clinical practice as a choice of individualized therapy, particularly in cancer treatment. Pharmacogenomics is an interdisciplinary field of genomics that deals with drug response, based on individual genetic makeup. Objective: The main genetic events associated with carcinogenesis activate oncogenes or inactivate tumor-suppressor genes. Therefore, drugs should be specific to inactivate or regulate these mutant genes and their protein products for effective cancer treatment. In this review, we summarize how polymedication decisions in cancer treatments based on the evaluation of cytochrome P450 (CYP450) polymorphisms are applied for pharmacogenetic assessment of anticancer therapy outcomes. Results: However, multiple genetic events linked, inactivating a single mutant gene product, may be insufficient to inhibit tumor progress. Thus, genomics and pharmacogenetics directly influence a patient’s response and aid in guiding clinicians to select the safest and most effective combination of medications for a cancer patient from the initial prescription. Conclusion: This review outlines the roles of oncogenes, the importance of cytochrome P450 (CYP450) in cancer susceptibility, and its impact on drug metabolism, proposing combined approaches to achieve precision therapy.

scholarly journals 3D Bioprinted cancer models: Revolutionizing personalized cancer therapy

2021 ◽  
Vol 14 (4) ◽  
pp. 101015
Author(s):  
Robin Augustine ◽  
Sumama Nuthana Kalva ◽  
Rashid Ahmad ◽  
Alap Ali Zahid ◽  
Shajia Hasan ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Cancer Models ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer

Preclinical investigations revealed possibilities for Salmonella tumor treatment. Bacteria can also be coupled to nanomaterials enabling drug-loading, photocatalytic and/or magnetic properties, using the bacteria's net negative charge

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Clinical Trials ◽  
Cancer Therapy ◽  
Cancer Treatment ◽  
Negative Charge ◽  
Human Cancer ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Preclinical Research ◽  
Immunodeficient Mice ◽  
Virulence Attenuation

Except in human clinical trials, preclinical tests showed the potential of Salmonella bacteria for tumor therapy. There are still various challenges to tackle before salmonella bacteria may be employed to treat human cancer. Due to its pathogenic nature, attenuation is essential to minimize the host's harmful effects of bacterial infection. Loss of anticancer efficacy from bacterial virulence attenuation can be compensated by giving therapeutic payloads to microorganisms. Bacteria can also be linked to micro-or nanomaterials with diverse properties, such as drug-loaded, photocatalytic and/or magnetic-sensing nanoparticles, using the net negative charge of the bacteria. Combining bacteria-mediated cancer treatment with other medicines that have been clinically shown to be helpful but have limits may provide surprising therapeutic results. Recently, this strategy has received attention and is underway. The use of live germs for cancer treatment has not yet been approved for human clinical trials. The non-invasive oral form of administration benefits from safety, making it more suitable for clinical cancer patients.Infection of live germs through systemic means, on the other hand, involves toxicity risk. Although Salmonella bacteria can be genetically manipulated with high tumor targeting, harm to normal tissues can not be excluded when medications with nonspecific toxicity are administered. It is preferred if the action of selected drugs may be restricted to the tumor site rather than healthy tissues, thereby boosting cancer therapy safety. In recent years, many regulatory mechanisms have been developed to manage pharmaceutical distribution through live bacterial vectors. Engineered salmonella can accumulate 1000 times greater than normal tissue density in the tumor. The QS-regulated mechanism, which initiates gene expression when bacterial density exceeds a particular threshold level, also promises Salmonella bacteria for targeted medication delivery. Nanovesicle structures of Salmonella bacteria can also be used as biocompatible nanocarriers to deliver functional medicinal chemicals in cancer therapy. Surface-modified nanovesicles preferably attach to tumor cells and are swallowed by receptor-mediated endocytosis before being destroyed to release packed drugs. The xenograft methodology, which comprises the implantation of cultivated tumor cell lines into immunodeficient mice, has often been used in preclinical research revealing favorable results about the anticancer effects of genetically engineered salmonella.

Imaging of TKI–Target Interactions for Personalized Cancer Therapy

2012 ◽  
Vol 93 (3) ◽  
pp. 239-241 ◽  
Author(s):  
A J Poot ◽  
P Slobbe ◽  
N H Hendrikse ◽  
A D Windhorst ◽  
GAMS van Dongen
Keyword(s):  
Cancer Therapy ◽  
Personalized Cancer Therapy ◽  
Personalized Cancer
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