Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - September 26, 2015 Category: Cancer & Oncology Source Type: research

Personalised Pathway Analysis Reveals Association between DNA Repair Pathway Dysregulation and Chromosomal Instability in Sporadic Breast Cancer
In this study, we performed a personalised pathway analysis independently for four large sporadic breast cancer cohorts to investigate the status of HR pathway dysregulation in individual sporadic breast tumours, its association with HR repair deficiency and its impact on tumour characteristics. (Source: Molecular Oncology)
Source: Molecular Oncology - September 24, 2015 Category: Cancer & Oncology Authors: Chao Liu, Sriganesh Srihari, Samir Lal, Benoît Gautier, Peter T. Simpson, Kum Kum Khanna, Mark A. Ragan, Kim-Anh Lê Cao Source Type: research

Sensitivity of plasma BRAF and NRAS cell-free DNA assays to detect metastatic melanoma in patients with low RECIST scores and non-RECIST disease progression
Melanoma lacks a clinically useful blood-based biomarker of disease activity to help guide patient management. To determine whether measurements of circulating, cell-free, tumor-associated BRAFmutant and NRASmutant DNA (ctDNA) have a higher sensitivity than LDH to detect metastatic disease prior to treatment initiation and upon disease progression we studied patients with unresectable stage IIIC/IV metastatic melanoma receiving treatment with BRAF inhibitor therapy or immune checkpoint blockade and at least 3 plasma samples obtained during their treatment course. (Source: Molecular Oncology)
Source: Molecular Oncology - September 22, 2015 Category: Cancer & Oncology Authors: Gregory A. Chang, Jyothirmayee S. Tadepalli, Yongzhao Shao, Yilong Zhang, Sarah Weiss, Eric Robinson, Cindy Spittle, Manohar Furtado, Dawne N. Shelton, George Karlin-Neumann, Anna Pavlick, Iman Osman, David Polsky Source Type: research

Sensitivity of plasma BRAFmutant and NRASmutant cell-free DNA assays to detect metastatic melanoma in patients with low RECIST scores and non-RECIST disease progression
Melanoma lacks a clinically useful blood-based biomarker of disease activity to help guide patient management. To determine whether measurements of circulating, cell-free, tumor-associated BRAFmutant and NRASmutant DNA (ctDNA) have a higher sensitivity than LDH to detect metastatic disease prior to treatment initiation and upon disease progression we studied patients with unresectable stage IIIC/IV metastatic melanoma receiving treatment with BRAF inhibitor therapy or immune checkpoint blockade and at least 3 plasma samples obtained during their treatment course. (Source: Molecular Oncology)
Source: Molecular Oncology - September 22, 2015 Category: Cancer & Oncology Authors: Gregory A. Chang, Jyothirmayee S. Tadepalli, Yongzhao Shao, Yilong Zhang, Sarah Weiss, Eric Robinson, Cindy Spittle, Manohar Furtado, Dawne N. Shelton, George Karlin-Neumann, Anna Pavlick, Iman Osman, David Polsky Source Type: research

Altered purinergic receptor-Ca signaling associated with hypoxia-induced epithelial-mesenchymal transition in breast cancer cells
Hypoxia is a feature of the microenvironment of many cancers and can trigger epithelial-mesenchymal transition (EMT), a process by which cells acquire a more invasive phenotype with enriched survival. A remodeling of adenosine 5´-triphosphate (ATP)-induced Ca2+ signaling via purinergic receptors is associated with epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells. Here, we assessed ATP-mediated Ca2+ signaling in a model of hypoxia-induced EMT in MDA-MB-468 cells. Like EGF, hypoxia treatment (1% O2) was also associated with a significant reduction in the sensitivity of MDA-MB-468 cells to ATP (EC5...
Source: Molecular Oncology - September 22, 2015 Category: Cancer & Oncology Authors: Iman Azimi, Hannah Beilby, Felicity M. Davis, Daneth L. Marcial, Paraic A. Kenny, Erik W. Thompson, Sarah J. Roberts-Thomson, Gregory R. Monteith Source Type: research

p53-Based strategy to reduce hematological toxicity of chemotherapy: A proof of principle study
p53 activation is a primary mechanism underlying pathological responses to DNA damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity.Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy. (Source: Molecular Oncology)
Source: Molecular Oncology - September 17, 2015 Category: Cancer & Oncology Authors: Chul S. Ha, Joel E. Michalek, Richard Elledge, Kevin R. Kelly, Suthakar Ganapathy, Hang Su, Carol A. Jenkins, Athanassios Argiris, Ronan Swords, Tony Y. Eng, Anand Karnad, Richard L. Crownover, Gregory P. Swanson, Martin Goros, Brad H. Pollock, Zhi-Min Y Source Type: research

p53-Based Strategy to Reduce Hematological Toxicity of Chemotherapy: A Proof of Principle Study
P53 activation is a primary mechanism underlying pathological responses to DNA-damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity.Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy. (Source: Molecular Oncology)
Source: Molecular Oncology - September 17, 2015 Category: Cancer & Oncology Authors: Chul S. Ha, Joel E. Michalek, Richard Elledge, Kevin R. Kelly, Suthakar Ganapathy, Hang Su, Carol A. Jenkins, Athanassios Argiris, Ronan Swords, Tony Y. Eng, Anand Karnad, Richard L. Crownover, Gregory P. Swanson, Martin Goros, Brad H. Pollock, Zhi-Min Yu Source Type: research

High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy
Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti-HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti-HER2 treatments. (Source: Molecular Oncology)
Source: Molecular Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Paolo Nuciforo, Sheeno Thyparambil, Claudia Aura, Ana Garrido-Castro, Marta Vilaro, Vicente Peg, José Jimenez, Rocio Vicario, Fabiola Cecchi, William Hoos, Jon Burrows, Todd Hembrough, Juan Carles Ferreres, José Perez-Garcia, Joaquin Arribas, Javier Cor Source Type: research

T-cell Receptor Profiling in Cancer
Immunosequencing is a platform technology that allows the enumeration, specification and quantification of each and every B- and/or T-cell in any biologic sample of interest. Thus, it provides an assessment of the level and distribution of all the clonal lymphocytes in any sample, and allows “tracking” of a single clone or multiple clones of interest over time or from tissue to tissue within a given patient. It is based on bias-controlled multiplex PCR and high-throughput sequencing, and it is highly accurate, standardized, and sensitive. (Source: Molecular Oncology)
Source: Molecular Oncology - September 15, 2015 Category: Cancer & Oncology Authors: Ilan Kirsch, Marissa Vignali, Harlan Robins Tags: Review Source Type: research

Transcriptional profiling of dividing tumor cells detects intratumor heterogeneity linked to cell proliferation in a brain tumor model
Intratumor heterogeneity is a primary feature of high-grade gliomas, complicating their therapy. As accumulating evidence suggests that intratumor heterogeneity is a consequence of cellular subsets with different cycling frequencies, we developed a method for transcriptional profiling of gliomas, using a novel technique to dissect the tumors into two fundamental cellular subsets, namely, the proliferating and non-proliferating cell fractions. The tumor fractions were sorted whilst maintaining their molecular integrity, by incorporating the thymidine analogue 5-ethynyl-2’-deoxyuridine into actively dividing cells. (Source...
Source: Molecular Oncology - September 10, 2015 Category: Cancer & Oncology Authors: Berwini B. Endaya, Paula Y.P. Lam, Adrian C.B. Meedeniya, Jiri Neuzil Source Type: research

Interleukin-33 predicts poor prognosis and promotes ovarian cancer cell growth and metastasis through regulating ERK and JNK signaling pathways
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer, it remains a huge challenge to understand the cellular and molecular mechanisms of the aggressive behaviour of EOC cells. Here we investigated the role of an immunomodulatory cytokine IL-33 and its receptor ST2 in mediating the growth and metastasis of EOC. Our data show that both IL-33 and ST2 were highly up-regulated in EOC tumours compared with normal ovary and ovarian benign tumours, and the expression levels were further increased in tumour tissues at the metastatic site. (Source: Molecular Oncology)
Source: Molecular Oncology - September 8, 2015 Category: Cancer & Oncology Authors: Xiaoguang Tong, Mark Barbour, Kezuo Hou, Chao Gao, Shuang Cao, Jingli Zheng, Yang Zhao, Rong Mu, Hui-Rong Jiang Source Type: research

mTORC1 and DNA-PKcs as Novel Molecular Determinants of Sensitivity to Chk1 Inhibition
Chk1 inhibitors are currently under clinical evaluation as single agents and in combination with cytotoxic chemotherapy. Understanding determinants of sensitivity and novel combinations is critical for further clinical development. (Source: Molecular Oncology)
Source: Molecular Oncology - August 25, 2015 Category: Cancer & Oncology Authors: Andrew J. Massey, Peter Stephens, Rebecca Rawlinson, Lauren McGurk, Ruth Plummer, Nicola J. Curtin Source Type: research

Genomic signatures for paclitaxel and gemcitabine resistance in breast cancer derived by machine learning
Increasingly, the effectiveness of adjuvant chemotherapy agents for breast cancer has been related to changes in the genomic profile of tumors. We investigated correspondence between growth inhibitory concentrations of paclitaxel and gemcitabine (GI50) and gene copy number, mutation, and expression first in breast cancer cell lines and then in patients. Genes encoding direct targets of these drugs, metabolizing enzymes, transporters, and those previously associated with chemoresistance to paclitaxel (n=31 genes) or gemcitabine (n=18) were analyzed. (Source: Molecular Oncology)
Source: Molecular Oncology - August 21, 2015 Category: Cancer & Oncology Authors: Stephanie N. Dorman, Katherina Baranova, Joan H.M. Knoll, Brad L. Urquhart, Gabriella Mariani, Maria Luisa Carcangiu, Peter K. Rogan Source Type: research

Resistance to BRAF inhibitors induces glutamine dependency in melanoma cells
BRAF inhibitors can extend progression-free and overall survival in melanoma patients whose tumors harbor mutations in BRAF. However, the majority of patients eventually develop resistance to these drugs. Here we show that BRAF mutant melanoma cells that have developed acquired resistance to BRAF inhibitors display increased oxidative metabolism and increased dependency on mitochondria for survival. Intriguingly, the increased oxidative metabolism is associated with a switch from glucose to glutamine metabolism and an increased dependence on glutamine over glucose for proliferation. (Source: Molecular Oncology)
Source: Molecular Oncology - August 19, 2015 Category: Cancer & Oncology Authors: Franziska Baenke, Barbara Chaneton, Matthew Smith, Niels Van Den Broek, Kate Hogan, Haoran Tang, Amaya Viros, Matthew Martin, Laura Galbraith, Maria R. Girotti, Nathalie Dhomen, Eyal Gottlieb, Richard Marais Source Type: research

Serum N-glycan analysis in breast cancer patients – relation to tumour biology and clinical outcome
Glycosylation and related processes play important roles in cancer development and progression, including metastasis. Several studies have shown that N-glycans have potential diagnostic value as cancer serum biomarkers. We have explored the significance of the abundance of particular serum N-glycan structures as important features of breast tumour biology by studying the serum glycome and tumour transcriptome (mRNA and miRNA) of 104 breast cancer patients. Integration of these types of molecular data allows us to study the relationship between serum glycans and transcripts representing functional pathways, such as metaboli...
Source: Molecular Oncology - August 18, 2015 Category: Cancer & Oncology Authors: Vilde D. Haakensen, Israel Steinfeld, Radka Saldova, Akram Asadi Shehni, Ilona Kifer, Bjørn Naume, Pauline M. Rudd, Anne-Lise Børresen-Dale, Zohar Yakhini Source Type: research