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Cancer Biomarkers and Genetics
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Genetic testing may encompass the analysis of gene(s), exomes, or even the entire genome. Genetic testing conducted to identify germline (inherited) gene mutations is typically performed on a blood, mouthwash, buccal swab, or banked DNA specimen. The purpose of germline genetic testing in the oncology setting is to identify the underlying genetic basis for the cancer predisposition in the family and subsequently use this information to guide treatment, follow-up, and make genetic testing available to at-risk family members. From the Washington Manual of Oncology.

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European urology 
CONTEXT: Although the widespread use of prostate-specific antigen (PSA) has led to an early detection of prostate cancer (PCa) and a reduction of metastatic disease at diagnosis, PSA remains one of the most controversial biomarkers due to its limited specificity. As part of emerging efforts to improve both detection and management decision making, a number of new genomic tools have recently been developed. OBJECTIVE: This review summarizes the ability of genomic biomarkers to recognize men at high risk of developing PCa, discriminate clinically insignificant and aggressive tumors, and facilitate the selection of therapies in patients with advanced disease. EVIDENCE ACQUISITION: A PubMed-based literature search was conducted up to May 2017. We selected the most recent and relevant original articles and clinical trials that have provided indispensable information to guide treatment decisions. EVIDENCE SYNTHESIS: Genome-wide association studies have identified several genetic polymorphisms and inherited variants associated with PCa susceptibility. Moreover, the urine-based assays SelectMDx, Mi-Prostate Score, and ExoDx have provided new insights into the identification of patients who may benefit from prostate biopsy. In men with previous negative pathological findings, Prostate Cancer Antigen 3 and ConfirmMDx predicted the outcome of subsequent biopsy. Commercially available tools (Decipher, Oncotype DX, and Prolaris) improved PCa risk stratification, identifying men at the highest risk of adverse outcome. Furthermore, other biomarkers could assist in treatment selection in castration-resistant PCa. AR-V7 expression predicts resistance to abiraterone/enzalutamide, while poly(ADP-ribose) polymerase-1 inhibitor and platinum-based chemotherapy could be indicated in metastatic patients who are carriers of mutations in DNA mismatch repair genes. CONCLUSIONS: Introduction of genomic biomarkers has dramatically improved the detection, prognosis, and risk evaluation of PCa. Despite the progress made in discovering suitable biomarker candidates, few have been used in a clinical setting. Large-scale and multi-institutional studies are required to validate the efficacy and cost utility of these new technologies. PATIENT SUMMARY: Prostate cancer is a heterogeneous disease with a wide variability. Genomic biomarkers in combination with clinical and pathological variables are useful tools to reduce the number of unnecessary biopsies, stratify low-risk from high-risk tumors, and guide personalized treatment decisions.
Oncology (5)
Prostatic Neoplasms (5), Neoplasms (2), more mentions
Annals of internal medicine 
Background: The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement. Objective: To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas. Design: Case-control study. Setting: Colonoscopy-controlled referral population from several centers. Participants: 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples). Measurements: Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples. Results: In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001). Limitation: Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples. Conclusion: Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening. Primary Funding Source: Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.
Oncology (17)
Adenoma (8), Neoplasms (7), Colorectal Neoplasms (2), more mentions
Clinical cancer research : an official journal of the American Association for Cancer Research 
Background: Breast cancer patients who do not respond to neoadjuvant therapy have a poor prognosis. There is a pressing need for novel targets and models for preclinical testing. Here we report characterization of breast cancer patient-derived xenografts (PDX) largely generated from residual tumors following neoadjuvant chemotherapy.Experimental Design: PDXs were derived from surgical samples of primary or locally recurrent tumors. Normal and tumor DNA sequencing, RNASeq, and reverse phase protein arrays (RPPA) were performed. Phenotypic profiling was performed by determining efficacy of a panel of standard and investigational agents.Results: Twenty-six PDXs were developed from 25 patients. Twenty-two were generated from residual disease following neoadjuvant chemotherapy, and 24 were from triple-negative breast cancer (TNBC). These PDXs harbored a heterogeneous set of genomic alterations and represented all TNBC molecular subtypes. On RPPA, PDXs varied in extent of PI3K and MAPK activation. PDXs also varied in their sensitivity to chemotherapeutic agents. PI3K, mTOR, and MEK inhibitors repressed growth but did not cause tumor regression. The PARP inhibitor talazoparib caused dramatic regression in five of 12 PDXs. Notably, four of five talazoparib-sensitive models did not harbor germline BRCA1/2 mutations, but several had somatic alterations in homologous repair pathways, including ATM deletion and BRCA2 alterations.Conclusions: PDXs capture the molecular and phenotypic heterogeneity of TNBC. Here we show that PARP inhibition can have activity beyond germline BRCA1/2 altered tumors, causing regression in a variety of molecular subtypes. These models represent an opportunity for the discovery of rational combinations with targeted therapies and predictive biomarkers. Clin Cancer Res; 23(21); 6468-77. ©2017 AACR.
Oncology (5)
Neoplasms (6), Breast Neoplasms (4), Residual Neoplasm (1), more mentions
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 
... condition (N=106) in postmenopausal, post-treatment breast cancer survivors, we investigated the influence of resistance training and changes in body composition on markers associated with cancer progression AbstractText: Measures included serum levels of insulin, IGF-1, IGFBP1-3, leptin, serum amyloid A (SAA), adiponectin, C-reactive protein (CRP), IL ...
Oncology (4)
Neoplasms (2), Breast Neoplasms (2), more mentions
Nature 
Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.
Oncology (4)
Pancreatic Neoplasms (3), Adenocarcinoma (2), Communicable Diseases (1), more mentions
Obesity (Silver Spring, Md.) 
AbstractText: The aim of this study was to explore the potential effects of diet-induced weight loss on molecular biomarkers of colorectal cancer risk in serum and colorectal tissue AbstractText: This single-arm exploratory study included 20 adults with BMI ≥ 30 kg/m(2) completing an 8-week, complete, low ...
Anti-Obesity and Weight Loss (6), Oncology (3)
Colorectal Neoplasms (2), Obesity (1), Insulin Sensitivity (1), more mentions
PloS one 
Videssa® Breast is a combinatorial proteomic biomarker assay (CPBA), comprised of Serum Protein Biomarkers (SPB) and Tumor Associated Autoantibodies (TAAb) integrated with patient-specific clinical data to produce a diagnostic score that reliably detects breast cancer (BC) as an adjunctive tool to imaging. The performance of Videssa® Breast was evaluated in the dense (a and b) and non-dense (c ...
Oncology (5)
Breast Neoplasms (5), Neoplasms (1), more mentions
Archives of pathology & laboratory medicine 
CitationSubset: AIM. CitationSubset: IM. DescriptorName: Biomarkers, Tumor. DescriptorName: Diagnosis, Differential. DescriptorName: Fusion Proteins, bcr-abl. DescriptorName: Histone-Lysine N-Methyltransferase. DescriptorName: Humans. DescriptorName: Immunohistochemistry. DescriptorName: Immunophenotyping. DescriptorName: Leukemia, Biphenotypic, Acute. DescriptorName: Myeloid-Lymphoid Leukemia Protein. DescriptorName: Practice Guidelines as Topic. DescriptorName: Prognosis. DescriptorName: Translocation, Genetic. DescriptorName: World Health Organization. Abstract: Mixed-phenotype acute leukemia (MPAL) is a heterogeneous category in ...
Oncology (5)
Leukemia (6), Lymphoid Leukemia (1), Neoplasms (1), more mentions
NPJ biofilms and microbiomes 
We link the high turnover metabotype to unreported microbial β-glucuronidases; inhibiting these enzymes may decrease irinotecan-dependent adverse drug responses in targeted subsets of patients. In total, this study reveals metagenomic mining of the microbiome, combined with metabolomics, as a non-invasive approach to develop biomarkers for colorectal cancer treatment outcomes.
Oncology (3)
Colorectal Neoplasms (3), Diarrhea (1), more mentions
European urology 
... the impact of WPRT on quality of life, clinical progression, and overall survival AbstractText: We evaluated patients with prostate cancer treated with radiation after surgery to remove the prostate. Both radiation to the pelvic lymph nodes and suppression of testosterone lowered the chance of increasing prostate-specific antigen (a marker for cancer returning) Keyword: Androgen deprivation therapy. Keyword: Biochemical failure.
Oncology (4)
Prostatic Neoplasms (3), Neoplasms (1), more mentions