Personalizing Oncology: Perspectives and Prospects

2013 ◽  
Vol 31 (15) ◽  
pp. 1904-1911 ◽  
Author(s):  
John Mendelsohn
Keyword(s):  
Clinical Trials ◽  
Molecular Targets ◽  
Targeted Drugs ◽  
Genetic Aberrations ◽  
Patients With Cancer ◽  
Reasonable Cost ◽  
Before And After ◽  
Cancer Medicine ◽  
And Performance ◽  
Selection Of

This article provides an overview of the research, beginning a century ago, that has led to the current use of genomically informed methods for selection of targeted therapies to treat individual patients with cancer—so-called precision cancer medicine. Until 1980, most research on cancer therapy was not targeted in the sense we use the word today. Since then, there has been an acceleration in research identifying genetic and molecular targets and in clinical trials using biomarkers that identify the presence of genetic or molecular markers in a patient's cancer to select appropriate targeted therapy. This approach has been made possible by increased knowledge of the genetic pathogenesis of cancer and by increased capacity to sequence genes and genomes in clinically useful timeframes and at a reasonable cost. However, many challenges and pitfalls remain in selecting optimal targets, interpreting data on genetic aberrations, designing effective targeted drugs and antibodies, dealing with resistance to treatments, identifying appropriate combinations of therapies, and performing the complex clinical trials that are required. Future clinical research with experimental targeted agents is likely to be more informative because of appropriate preselection of patients enrolled onto trials and performance of genetic and molecular studies on specimens of a patient's cancer before and after treatment.

scholarly journals Early-Life Dam-Calf Contact and Grazing Experience Influence Post-Weaning Behavior and Herbage Selection of Dairy Calves in the Short Term

2020 ◽  
Vol 7 ◽  
Author(s):  
Alessandra Nicolao ◽  
Mauro Coppa ◽  
Matthieu Bouchon ◽  
Enrico Sturaro ◽  
Dominique Pomiès ◽  
...  
Keyword(s):  
Early Life ◽  
Daily Activities ◽  
Dairy Calves ◽  
Short Term ◽  
Start Time ◽  
Grazing Behavior ◽  
Reciprocal Interactions ◽  
Before And After ◽  
And Performance ◽  
Selection Of

Rearing dairy calves with their mothers could teach them how to graze, optimizing grass use, and improving their welfare and performance. We tested the short-term effects of dam-calf contact experience on grazing and social behavior of weaned calves, monitored over seven days for their first post-weaning grazing experience. “Dam” (D) calves were reared and grazed with their mothers until weaning. “Mixed” calves (M) were separated from their mothers after 4 ± 0.5 weeks, they experienced dam-calf contact, but not grazing. “Standard” (S) calves had never experienced either dam-calf contact (separated at birth) or grazing. Each group grazed an equivalent pasture plot offering heterogeneous herbage. Scan sampling of calves' activities was performed every 5 min, 6 h per day, on Days 0, 1, 2, 3, and 7. Daily, the time when calves started grazing after introduction to pasture, and the number and duration of their grazing cycles were measured. Daily activities were differentiated into ingestion, rumination, and idling. The proportion of time that calves spent grouped with other individuals or isolated, and standing or lying were recorded. When grazing, their bites were characterized by botanical family group, height of the selected bite and vegetation status. Individual average daily gains from the 2-week periods before and after grazing were calculated, and were equivalent between groups (313 ± 71 g/d). On Day 0, D-calves started grazing immediately (1 ± 4.1 min), unlike M- and S-calves (39 ± 4.1 and 23 ± 4.1 min), and D-calves grazed patches of dry grass 21.7 times less than M-calves and 16.9 times less than S-calves. Dry herbage patch preference and grazing start time differences disappeared on Day 1. Calves spent the same time ingesting and idling, but M-calves spent on average 1.6 times less ruminating than D- or S-calves. The D-calves showed grazing behavior similar to that of adult cows, selecting grasses throughout pasture utilization, although legumes and forbs were present in the grazed layer. On the contrary, M- and S-calves did not express any specific preference. The S-calves spent more time isolated but had more positive reciprocal interactions than the calves in the other groups.

scholarly journals Clinical Utility of Precision Medicine in Pediatric Oncology: A Systematic Review

2021 ◽  
pp. 1088-1102
Author(s):  
Justin Lee ◽  
Lynn Gillam ◽  
Keshini Visvanathan ◽  
Jordan R. Hansford ◽  
Maria C. McCarthy
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Pediatric Oncology ◽  
Observational Studies ◽  
Clinical Utility ◽  
Molecular Targets ◽  
Molecular Techniques ◽  
Targeted Drugs ◽  
Outcome Reporting

PURPOSE Precision medicine uses advanced molecular techniques to guide the use of targeted therapeutic drugs and is an emerging paradigm in pediatric oncology. Clinical evidence related to the efficacy of many novel targeted drugs, however, is currently very limited given the rarity of pediatric cancer and the lack of published evidence for the use of these drugs in children. This systematic review aimed to evaluate the existing evidence for the feasibility and clinical efficacy of precision medicine in pediatric oncology. METHODS A systematic review was conducted using the PubMed, Medline, and Embase databases. Clinical trials and observational studies, which used molecular assays such as whole-exome sequencing to identify molecular targets that guided the allocation of targeted cancer drugs and reported clinical outcomes, were included in this review. RESULTS Twenty-one clinical trials and observational studies were identified, collectively enrolling 1,408 pediatric patients across nine countries. Therapeutic targets were found in 647 patients (46.0%); however, only 175 of these patients (27.0%) received a targeted drug. Objective responses were recorded for 73 (41.7%) of these 175 patients, only 5.2% of the total sample. Inconsistent outcome reporting and limited comparison with conventional treatment hindered evaluation of the clinical utility of precision medicine. CONCLUSION Precision medicine can feasibly identify molecular targets in a clinical setting. However, the inaccessibility of targeted drugs is a significant barrier, restricting the exploration of its therapeutic potential in pediatric oncology. Future clinical trials should endeavor to link the molecular testing results with access to targeted drugs and standardize outcome reporting to advance understanding of the benefits of this novel paradigm in improving patient outcomes.

scholarly journals Molecular Targets, Pathways, and Therapeutic Implications for Hepatocellular Carcinoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5232
Author(s):  
Jun Gong ◽  
Jeremy Chuang ◽  
May Cho ◽  
Kyra Toomey ◽  
Andrew Hendifar ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Targeted Therapies ◽  
Cancer Mortality ◽  
Molecular Targets ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Therapeutic Implications ◽  
The Past ◽  
Selection Of

Hepatocellular carcinoma (HCC) represents one of the leading causes of cancer mortality worldwide. While significant advances have been made for the treatment of advanced hepatocellular carcinoma in the past few years, the prognosis remains poor and effective biomarkers to guide selection of therapies remain noticeably absent. However, several targeted therapies have been approved in the past few years that have improved the outlook for this disease. In this review, we will highlight the recent therapies approved for the treatment of advanced HCC and discuss promising therapeutic options, targets, and pathways for drug development and consideration for future clinical trials.

L-arginine effect on inflammatory mediators: A systematic review of randomized controlled clinical trials

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Seyed Reza Mirhafez ◽  
Mitra Hariri
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Inflammatory Mediators ◽  
Randomized Clinical Trials ◽  
Randomized Controlled Clinical Trials ◽  
Patients With Cancer ◽  
Reactive Protein ◽  
Randomized Controlled ◽  
Human Adults ◽  
Factor Α

Abstract. L-arginine is an important factor in several physiological and biochemical processes. Recently, scientists studied L-arginine effect on inflammatory mediators such as C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We conducted a systematic review on randomized controlled trials assessing L-arginine effect on inflammatory mediators. We searched data bases including Google scholar, ISI web of science, SCOPUS, and PubMed/Medline up to April 2019. Randomized clinical trials assessing the effect of L-arginine on inflammatory mediators in human adults were included. Our search retrieved eleven articles with 387 participants. Five articles were on patients with cancer and 6 articles were on adults without cancer. L-arginine was applied in enteral form in 5 articles and in oral form in 6 articles. Eight articles were on both genders, two articles were on women, and one article was on men. L-arginine could not reduce inflammatory mediators among patients with and without cancer except one article which indicated that taking L-arginine for 6 months decreased IL-6 among cardiopathic nondiabetic patients. Our results indicated that L-arginine might not be able to reduce selected inflammatory mediators, but for making a firm decision more studies are needed to be conducted with longer intervention duration, separately on male and female and with different doses of L-arginine.

Rationale for heparin treatment of colon cancer

2000 ◽  
Vol 20 (03) ◽  
pp. 136-142 ◽  
Author(s):  
D. L. Ornstein ◽  
L. R. Zacharski
Keyword(s):  
Clinical Trials ◽  
Substantial Improvement ◽  
Patients With Cancer ◽  
Coagulation Mechanism ◽  
Anticoagulant Drug ◽  
Cancer Outcome ◽  
Meta Analyses ◽  
Improvement In Survival ◽  
Spectrum Of Patients ◽  
To Receive

SummaryIt is widely known that the systemic blood coagulation mechanism is often activated in malignancy, leading to an increased incidence of vascular thromboses in patients with cancer. It is not widely appreciated, however, that products of the coagulation mechanism may also support tumor growth and dissemination. Interest in this approach to cancer therapy has surged recently because of mounting evidence that the familiar anticoagulant drug, heparin, may impede tumor progression. Heparin has the capacity to modify angiogenesis, growth factor and protease activity, immune function, cell proliferation and gene expression in ways that may block malignant dissemination. Clinical trials in which heparin has been administered to a broad spectrum of patients to prevent or treat thrombosis have unexpectedly shown improvement in survival in the subset of patients with malignancy entered to these studies. Meta-analyses of clinical trials comparing unfractionated (UF) versus low molecular weight (LMW) heparin treating venous thromboembolism suggest that there may be substantial improvement in cancer outcome in patients with malignancy randomized to receive LMW heparin. These findings provide a rationale for definitive clinical trials of LMW heparin in cancer, and the results of several such studies that are currently underway are awaited with interest.

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

PILONIDAL DISEASE: CHANGES IN UNDERSTANDING OF ETIOLOGY, PATHOGENESIS AND APPROACH TO TREATMENT

2019 ◽  
Vol 72 (8) ◽  
pp. 1559-1565
Author(s):  
Viktor Konoplitskyi ◽  
Ruslan Shavliuk ◽  
Dmytro Dmytriiev ◽  
Kostiantyn Dmytriiev ◽  
Oleksii Kyrychenko ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Pilonidal Sinus ◽  
Randomized Clinical Trials ◽  
Web Of Science ◽  
Surgical Intervention ◽  
Pilonidal Disease ◽  
Treatment Methods ◽  
Principles Of Treatment ◽  
Selection Of

Data from Web of Science, SCOPUS, Pub Med, Medline, E-library, and other sources was used in writing this article. The main focus was directed towards literature written in English. The selection of literature was based on such concepts as: etiopathogenesis, historical principles of treatment, methods of surgical and non-surgical intervention. Data from metanalysis publications and randomized clinical trials pertaining to the treatment of the pilonidal sinus at various stages of its formation was used, as well.

A Biomarker Combining Imaging and Neuropsychological Assessment for Tracking Early Alzheimer's Disease in Clinical Trials

2018 ◽  
Vol 15 (5) ◽  
pp. 429-442 ◽  
Author(s):  
Nishant Verma ◽  
S. Natasha Beretvas ◽  
Belen Pascual ◽  
Joseph C. Masdeu ◽  
Mia K. Markey ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Latent Variable ◽  
Brain Regions ◽  
Disease Assessment ◽  
Latent Variable Analysis ◽  
The Relationship ◽  
Selection Of

Background: Combining optimized cognitive (Alzheimer's Disease Assessment Scale- Cognitive subscale, ADAS-Cog) and atrophy markers of Alzheimer's disease for tracking progression in clinical trials may provide greater sensitivity than currently used methods, which have yielded negative results in multiple recent trials. Furthermore, it is critical to clarify the relationship among the subcomponents yielded by cognitive and imaging testing, to address the symptomatic and anatomical variability of Alzheimer's disease. Method: Using latent variable analysis, we thoroughly investigated the relationship between cognitive impairment, as assessed on the ADAS-Cog, and cerebral atrophy. A biomarker was developed for Alzheimer's clinical trials that combines cognitive and atrophy markers. Results: Atrophy within specific brain regions was found to be closely related with impairment in cognitive domains of memory, language, and praxis. The proposed biomarker showed significantly better sensitivity in tracking progression of cognitive impairment than the ADAS-Cog in simulated trials and a real world problem. The biomarker also improved the selection of MCI patients (78.8±4.9% specificity at 80% sensitivity) that will evolve to Alzheimer's disease for clinical trials. Conclusion: The proposed biomarker provides a boost to the efficacy of clinical trials focused in the mild cognitive impairment (MCI) stage by significantly improving the sensitivity to detect treatment effects and improving the selection of MCI patients that will evolve to Alzheimer’s disease.

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