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https://www.readbyqxmd.com/read/28344745/can-molecular-biomarkers-replace-a-clinical-risk-score-for-resectable-colorectal-liver-metastasis
#1
EDITORIAL
Torhild Veen, Kjetil Søreide
In resectable colorectal liver metastasis (CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases (both resectable and non-resectable) and the shift in indication from "what is taken out" (e...
March 15, 2017: World Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28340378/current-fda-approved-treatments-for-non-small-cell-lung-cancer-and-potential-biomarkers-for-its-detection
#2
REVIEW
Karla A Ruiz-Ceja, Yolanda I Chirino
BACKGROUND: Lung cancer is the leading worldwide cancer with almost 1.5 million deaths every year. Some drugs for lung cancer treatment have been available on the market for decades, but novel drugs have emerged promising better outcomes, especially for Non-Small Cell Lung Cancer (NSCLC), which represents 75% of lung cancer cases. However, how much do drugs have evolved for NSCLC treatment? Are they sharing the same mechanism of action? AIM: In this review we analyzed how the approved drugs by Federal Drug Agency for NSCLC have advanced in the last four decades identifying shared mechanism of action of medicines against NSCLC treatment and some of the potential biomarkers for early detection...
March 21, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28337711/circulating-tumor-dna-for-mutation-detection-and-identification-of-mechanisms-of-resistance-in-non-small-cell-lung-cancer
#3
REVIEW
Kay T Yeung, Soham More, Brian Woodward, Victor Velculescu, Hatim Husain
Targeted therapies have changed the treatment landscape of non-small cell lung cancer over the past decade. Analyses of cell free circulating tumor DNA (ctDNA) provide a non-invasive and robust approach for cancer diagnosis and prognosis, real-time monitoring of treatment response, and the identification of appropriate therapeutic targets based on the detection of tumor genetic aberrations. Recent improvements in the sensitivity, specificity, and feasibility of ctDNA detection assays allow the possibility for implementation into clinical practice...
March 24, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28335812/cancerlocator-non-invasive-cancer-diagnosis-and-tissue-of-origin-prediction-using-methylation-profiles-of-cell-free-dna
#4
Shuli Kang, Qingjiao Li, Quan Chen, Yonggang Zhou, Stacy Park, Gina Lee, Brandon Grimes, Kostyantyn Krysan, Min Yu, Wei Wang, Frank Alber, Fengzhu Sun, Steven M Dubinett, Wenyuan Li, Xianghong Jasmine Zhou
We propose a probabilistic method, CancerLocator, which exploits the diagnostic potential of cell-free DNA by determining not only the presence but also the location of tumors. CancerLocator simultaneously infers the proportions and the tissue-of-origin of tumor-derived cell-free DNA in a blood sample using genome-wide DNA methylation data. CancerLocator outperforms two established multi-class classification methods on simulations and real data, even with the low proportion of tumor-derived DNA in the cell-free DNA scenarios...
March 24, 2017: Genome Biology
https://www.readbyqxmd.com/read/28330468/tumor-burden-monitoring-using-cell-free-tumor-dna-could-be-limited-by-tumor-heterogeneity-in-advanced-breast-cancer-and-should-be-evaluated-together-with-radiographic-imaging
#5
José Angel García-Saenz, Patricia Ayllón, Marion Laig, Daniel Acosta-Eyzaguirre, Marta García-Esquinas, Myriam Montes, Julián Sanz, Miguel Barquín, Fernando Moreno, Vanesa Garcia-Barberan, Eduardo Díaz-Rubio, Trinidad Caldes, Atocha Romero
BACKGROUND: Accurate measurement of tumor burden in breast cancer disease is essential to improve the clinical management of patients. In this study, we evaluate whether the fluctuations in the fraction of PIK3CA mutant allele correlates with tumor response according to RECIST criteria and tumor markers quantification. METHODS: Eighty six plasma samples were analyzed by digital PCR using Rare Mutation Assays for E542K, E545K and H1047R. Mutant cfDNA and tumor markers CA15-3 and CEA were compared with radiographic imaging...
March 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28328955/treatment-monitoring-in-metastatic-colorectal-cancer-patients-by-quantification-and-kras-genotyping-of-circulating-cell-free-dna
#6
Andreas W Berger, Daniel Schwerdel, Hanna Welz, Ralf Marienfeld, Stefan A Schmidt, Alexander Kleger, Thomas J Ettrich, Thomas Seufferlein
Treatment of metastatic colorectal cancer (CRC) has continuously improved over the last decade. However, disease monitoring remains underdeveloped and mostly dependent on imaging e.g. RECIST 1.1 criteria. The genetic landscape of individual cancers and subsequently occurring treatment-induced evolution remain neglected in current surveillance strategies. Novel biomarkers demand minimally invasive and repetitive tracking of the cancer mutagenome for therapy stratification and to make prognostic predictions. Carcinoembryonic antigen (CEA), a routinely used tumor marker for CRC, does not meet these goals and thus prevents its use as a reliable monitoring tool...
2017: PloS One
https://www.readbyqxmd.com/read/28327951/hpv16-dna-and-integration-in-normal-and-malignant-epithelium-implications-for-the-etiology-of-laryngeal-squamous-cell-carcinoma
#7
X Chen, L Gao, E M Sturgis, Z Liang, Y Zhu, X Xia, X Zhu, X Chen, G Li, Z Gao
Background: Molecular evidence suggests that human papillomavirus (HPV) has a role in the etiology of oropharyngeal squamous cell carcinoma. However, the role of HPV in laryngeal squamous cell carcinoma (LSCC) is unclear. Patients and Methods: We conducted a case-control study using tumor tissue specimens from 300 LSCC patients and vocal cord polyp specimens from 300 cancer-free controls. HPV genotype, HPV16 viral load and viral integration status, and p16 expression were determined...
January 23, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327944/a-phase-2-randomized-double-blind-placebo-%C3%A2-controlled-study-of-chemo-immunotherapy-combination-using-motolimod-with-pegylated-liposomal-doxorubicin-in-recurrent-or-persistent-ovarian-cancer-a-gynecologic-oncology-group-partners-study
#8
B J Monk, M F Brady, C Aghajanian, H A Lankes, T Rizack, J Leach, J M Fowler, R Higgins, P Hanjani, M Morgan, R Edwards, W Bradley, T Kolevska, P Foukas, E Swisher, K S Anderson, R Gottardo, J K Bryan, M Newkirk, K L Manjarrez, R S Mannel, R M Hershberg, G Coukos
Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo...
February 21, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28325688/current-and-emerging-molecular-tests-for-human-papillomavirus-related-neoplasia-in-the-genomic-era
#9
REVIEW
Sixto M Leal, Margaret L Gulley
Laboratory tests have a key role in preventing human papillomavirus (HPV)-driven carcinomas and in guiding therapeutic interventions. An understanding of the virology, immunology, and carcinogenesis of HPV is essential for choosing appropriate diagnostic test modalities and developing new and even more effective cancer prevention strategies. HPV infects basal epithelial cells on multiple surfaces and induces carcinoma primarily in the cervix and the oropharynx. HPV types are stratified as high risk or low risk based on their carcinogenic potential, driven largely by viral interference with cell cycle regulation and the DNA damage response to promote continuous cell division while thwarting apoptosis, which enables mutation accumulation...
March 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28323123/circumventing-intratumoral-heterogeneity-to-identify-potential-therapeutic-targets-in-hepatocellular-carcinoma
#10
Ao Huang, Xin Zhao, Xin-Rong Yang, Fu-Qiang Li, Xin-Lan Zhou, Kui Wu, Xin Zhang, Qi-Man Sun, Ya Cao, Hong-Mei Zhu, Xiang-Dong Wang, Huan-Ming Yang, Jian Wang, Zhao-You Tang, Yong Hou, Jia Fan, Jian Zhou
BACKGROUND AND AIMS: Intratumoral heterogeneity (ITH) challenges identifying mutations with target therapy potential whereas circulating cell-free DNAs (cfDNAs) in blood could possibly reflect the entire mutation spectrum in certain tumors. We investigated how to minimize the limit of ITH for profiling hepatocellular carcinoma (HCC). METHODS: Thirty-two multi-regional tumor samples from five patients were subjected to whole exome sequencing (WES) and targeted deep sequencing (TDS); matched preoperative cfDNAs were sequenced accordingly...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28320758/tumor-cell-free-dna-copy-number-instability-predicts-therapeutic-response-to-immunotherapy
#11
Glen J Weiss, Julia Beck, Donald P Braun, Kristen Bornemann-Kolatzki, Heather Barilla, Rhiannon Cubello, Walter Quan, Ashish Sangal, Vivek Khemka, Jordan Waypa, William M Mitchell, Howard Urnovitz, Ekkehard Schütz
PURPOSE: Chromosomal instability is a fundamental property of cancer, which can be quantified by Next Generation Sequencing (NGS) from plasma/serum derived cell-free DNA (cfDNA). We hypothesized that cfDNA could be used as a real time surrogate for imaging analysis of disease status as a function of response to immunotherapy and as a more reliable tool than tumor biomarkers. EXPERIMENTAL DESIGN: Plasma cfDNA sequences from 56 patients with diverse advanced cancers, were prospectively collected and analyzed in a single-blinded study for copy number variations, expressed as a quantitative chromosomal number instability (CNI) score versus 126 non-cancer controls in a training set of 23 and a blinded validation set of 33...
March 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28314870/perillyl-alcohol-a-pleiotropic-natural-compound-suitable-for-brain-tumor-therapy-targets-free-radicals
#12
REVIEW
Aline C Gomes, Angélica L Mello, Manuel G Ribeiro, Diogo G Garcia, Clovis O Da Fonseca, Marcela D'Alincourt Salazar, Axel H Schönthal, Thereza Quirico-Santos
Monoterpenes such as limonene and perillyl alcohol (POH) are promising natural compounds with pro-oxidant properties partly due to endoplasmic reticulum (ER) stress-induced cytotoxicity, and antioxidant activity owing to their activity as free radical scavengers, inhibition of coenzyme Q synthesis, activation of antioxidant-responsive elements (inducing detoxification enzymes) and induction of apoptosis. Activation of ER-stress responses generates reactive oxygen species (ROS), which are highly reactive free radicals mainly produced during mitochondrial electron transfer for adenosine triphosphate (ATP) synthesis...
March 17, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28314286/safety-and-tolerance-of-d-l-methadone-in-combination-with-chemotherapy-in-patients-with-glioma
#13
Julia Onken, Claudia Friesen, Peter Vajkoczy, Martin Misch
BACKGROUND/AIM: D,L-Methadone increases sensitivity toward chemotherapy of different tumor cell populations. We evaluated the safety and tolerance of additional use of D,L-methadone in patients with glioma in combination with chemotherapy. PATIENTS AND METHODS: The dosage, duration of therapy and side-effects related to D,L-methadone were recorded in 27 patients. Toxicity was assessed accordingly to the Common Toxicity Criteria (CTC) of the National Cancer Institute...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28302137/mutations-of-crebbp-and-socs1-are-independent-prognostic-factors-in-diffuse-large-b-cell-lymphoma-mutational-analysis-of-the-sakk-38-07-prospective-clinical-trial-cohort
#14
Darius Juskevicius, David Jucker, Dirk Klingbiel, Christoph Mamot, Stephan Dirnhofer, Alexandar Tzankov
BACKGROUND/PURPOSE: Recently, the mutational background of diffuse large B cell lymphoma (DLBCL) has been revealed, identifying specific genetic events that drive lymphomagenesis. However, the prognostic value of these mutations remains to be determined. Prognostic biomarkers in DLBCL are urgently needed, since the current clinical parameter-based factors (e.g., International Prognostic Index (IPI)) are insufficient, particularly in identifying patients with poor prognosis who might benefit from alternative treatments...
March 17, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28301276/epigenetic-alterations-as-biomarkers-in-pancreatic-ductal-adenocarcinoma
#15
Pascal Syren, Roland Andersson, Monika Bauden, Daniel Ansari
Pancreatic ductal adenocarcinoma (PDAC) prognosis remains very poor and has only marginally improved during the last decades. Epigenetic alterations have been the focus of many recent studies and offer valuable options for PDAC detection, prognosis and treatment. DNA methylation, histone modifications and microRNA (miR) level changes can be used as biomarkers. These alterations occur early in carcinogenesis and may be specific for PDAC. Additionally, epigenetic alterations can be analyzed from cell-free DNA, free-circulating nucleosomes or shed tumor cells in blood...
March 16, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28299955/niraparib-for-the-treatment-of-ovarian-cancer
#16
Yada Kanjanapan, Stephanie Lheureux, Amit M Oza
Introduction Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic...
March 16, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28298070/pulmonary-injury-associated-with-radiation-therapy-assessment-complications-and-therapeutic-targets
#17
REVIEW
Rasmi Rajan Radha, Guruvayoorappan Chandrasekharan
Pulmonary injury is more common in patients undergoing radiation therapy for lungs and other thoracic malignancies. Recently with the use of most-advanced technologies powerful doses of radiation can be delivered directly to tumor site with exquisite precision. The awareness of technical and clinical parameters that influence the chance of radiation induced lung injury is important to guide patient selection and toxicity minimization strategies. At the cellular level, radiation activates free radical production, leading to DNA damage, apoptosis, cell cycle changes, and reduced cell survival...
March 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28285688/plasma-epidermal-growth-factor-receptor-mutation-testing-with-a-chip-based-digital-pcr-system-in-patients-with-advanced-non-small-cell-lung-cancer
#18
Norimitsu Kasahara, Hirotsugu Kenmotsu, Masakuni Serizawa, Rina Umehara, Akira Ono, Yasushi Hisamatsu, Kazushige Wakuda, Shota Omori, Kazuhisa Nakashima, Tetsuhiko Taira, Tateaki Naito, Haruyasu Murakami, Yasuhiro Koh, Keita Mori, Masahiro Endo, Takashi Nakajima, Masanobu Yamada, Masatoshi Kusuhara, Toshiaki Takahashi
OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation testing is a companion diagnostic to determine eligibility for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC). Recently, plasma-based EGFR testing by digital polymerase chain reaction (dPCR), which enables accurate quantification of target DNA, has shown promise as a minimally invasive diagnostic. Here, we aimed to evaluate the accuracy of a plasma-based EGFR mutation test developed using chip-based dPCR-based detection of 3 EGFR mutations (exon 19 deletions, L858R in exon 21, and T790M in exon 20)...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28274957/an-acquired-her2-t798i-gatekeeper-mutation-induces-resistance-to-neratinib-in-a-patient-with-her2-mutant-driven-breast-cancer
#19
Ariella B Hanker, Monica Red Brewer, Jonathan H Sheehan, James P Koch, Gregory R Sliwoski, Rebecca Nagy, Richard Lanman, Michael F Berger, David M Hyman, David B Solit, Jie He, Vincent Miller, Richard E Cutler, Alshad S Lalani, Darren Cross, Christine M Lovly, Jens Meiler, Carlos L Arteaga
We report a HER2T798I gatekeeper mutation in a patient with HER2L869R-mutant breast cancer with acquired resistance to neratinib. Laboratory studies suggested that HER2L869R is a neratinib-sensitive, gain-of-function mutation that upon dimerization with mutant HER3E928G, also present in the breast cancer, amplifies HER2 signaling. The patient was treated with neratinib and exhibited a sustained partial response. Upon clinical progression, HER2T798I was detected in plasma tumor cell-free DNA. Structural modeling of this acquired mutation suggested that the increased bulk of isoleucine in HER2T798I reduces neratinib binding...
March 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28265230/electrotransfer-of-plasmid-dna-radiosensitizes-b16f10-tumors-through-activation-of-immune-response
#20
Monika Savarin, Urska Kamensek, Maja Cemazar, Richard Heller, Gregor Sersa
BACKGROUND: Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors. MATERIALS AND METHODS: The murine melanoma B16F10 tumors, growing on the back of C57Bl/6 mice, were treated by triple gene electrotransfer and irradiation...
March 1, 2017: Radiology and Oncology
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