Challenges in circulating tumor cell detection by the CellSearch system
Enumeration and characterization of circulating tumor cells (CTC) hold the promise of a real time liquid biopsy. They are however present in a large background of hematopoietic cells making their isolation technically challenging. In 2004, the CellSearch system was introduced as the first and only FDA cleared method designed for the enumeration of circulating tumor cells in 7.5 mL of blood. Presence of CTC detected by CellSearch is associated with poor prognosis in metastatic carcinomas. CTC remaining in patients after the first cycles of therapy indicates a futile therapy. (Source: Molecular Oncology)
Source: Molecular Oncology - December 24, 2015 Category: Cancer & Oncology Authors: Kiki C. Andree, Guus van Dalum, Leon WMM. Terstappen Tags: Review Source Type: research
Excellent Translational Research in Oncology: a Journey Towards Novel and More Effective Anti-cancer Therapies
Comprehensive Cancer Centres (CCCs) serve as critical drivers for improving cancer survival. In Europe, we have developed an Excellence Designation System (EDS) consisting of criteria to assess "excellence" of CCCs in translational research (bench to bedside and back), with the expectation that many European CCCs will aspire to this status. (Source: Molecular Oncology)
Source: Molecular Oncology - December 22, 2015 Category: Cancer & Oncology Authors: A. Rajan, A. Berns, U. Ringborg, J. Celis, B. Ponder, C. Caldas, D. Livingston, R.G. Bristow, T.T. Hecht, T. Tursz, H. van Luenen, P. Bono, T. Helander, K. Seamon, J.F. Smyth, D. Louvard, A. Eggermont, W.H. van Harten Tags: Science Policy Source Type: research
Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals SNORA55 as a driver of prostate cancer progression
Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered “housekeeping” genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa.We performed RNA Sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. (Source: Molecular Oncology)
Source: Molecular Oncology - December 21, 2015 Category: Cancer & Oncology Authors: Francesco Crea, Luca Quagliata, Agnieszka Michael, Hui Hsuan Liu, Paolo Frumento, Arun A. Azad, Hui Xue, Larissa Pikor, Akira Watahiki, Rudolf Morant, Serenella Eppenberger-Castori, Yuwei Wang, Abhijit Parolia, Kim A. Lennox, Wan L. Lam, Martin Gleave, Ki Source Type: research
Monitoring vascular normalization induced by antiangiogenic treatment with 18F-fluoromisonidazole-PET
Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with 18F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib. (Source: Molecular Oncology)
Source: Molecular Oncology - December 21, 2015 Category: Cancer & Oncology Authors: Elena Hernández-Agudo, Tamara Mondejar, Maria Luisa Soto-Montenegro, Diego Megías, Silvana Mouron, Jesus Sanchez, Manuel Hidalgo, Pedro Pablo Lopez-Casas, Francisca Mulero, Manuel Desco, Miguel Quintela-Fandino Source Type: research
Integrated analysis of the prostate cancer small-nucleolar transcriptome reveals as a driver of prostate cancer progression
Metastasis is the primary cause of death in prostate cancer (PCa) patients. Small nucleolar RNAs (snoRNAs) have long been considered “housekeeping” genes with no relevance for cancer biology. Emerging evidence has challenged this assumption, suggesting that snoRNA expression is frequently modulated during cancer progression. Despite this, no study has systematically addressed the prognostic and functional significance of snoRNAs in PCa.We performed RNA Sequencing on paired metastatic/non-metastatic PCa xenografts derived from clinical specimens. (Source: Molecular Oncology)
Source: Molecular Oncology - December 21, 2015 Category: Cancer & Oncology Authors: Francesco Crea, Luca Quagliata, Agnieszka Michael, Hui Hsuan Liu, Paolo Frumento, Arun A. Azad, Hui Xue, Larissa Pikor, Akira Watahiki, Rudolf Morant, Serenella Eppenberger-Castori, Yuwei Wang, Abhijit Parolia, Kim A. Lennox, Wan L. Lam, Martin Gleave, Ki Source Type: research
Monitoring vascular normalization induced by antiangiogenic treatment with F-fluoromisonidazole-PET
Rationalization of antiangiogenics requires biomarkers. Vascular re-normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with 18F-misonidazole ([18F]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib. (Source: Molecular Oncology)
Source: Molecular Oncology - December 21, 2015 Category: Cancer & Oncology Authors: Elena Hernández-Agudo, Tamara Mondejar, Maria Luisa Soto-Montenegro, Diego Megías, Silvana Mouron, Jesus Sanchez, Manuel Hidalgo, Pedro Pablo Lopez-Casas, Francisca Mulero, Manuel Desco, Miguel Quintela-Fandino Source Type: research
Receptor tyrosine kinase gene expression profiles of Ewing sarcomas reveal ROR1 as a potential therapeutic target in metastatic disease
Receptor tyrosine kinases (RTKs) have provided molecular targets for the development of novel, prognosis-improving agents in many cancers; however, resistances to these therapies occur. On the cellular level, one resistance mechanism is attributed to functional RTK redundancies and compensatory cross-signaling, leading to perception of RTKs as signaling and target networks. To provide a basis for better exploitation of this network in Ewing sarcoma, we generated comprehensive qPCR gene expression profiles of RTKs in Ewing sarcoma cell lines and 21 untreated primary tumors. (Source: Molecular Oncology)
Source: Molecular Oncology - December 20, 2015 Category: Cancer & Oncology Authors: Jenny Potratz, Amelie Tillmanns, Philipp Berning, Eberhard Korsching, Christiane Schaefer, Birgit Lechtape, Carolin Schleithoff, Rebekka Unland, Karl-Ludwig Schäfer, Carsten Müller-Tidow, Heribert Jürgens, Uta Dirksen Source Type: research
Editorial Board
(Source: Molecular Oncology)
Source: Molecular Oncology - December 18, 2015 Category: Cancer & Oncology Source Type: research
The transcription factors slug (snai2) and snail (snai1) regulate phospholipase d (pld) promoter in opposite ways towards cancer cell invasion
Slug (SNAI2) and Snail (SNAI1) are master regulatory transcription factors for organogenesis and wound healing, and they are involved in the epithelial-mesenchymal transition (EMT) of cancer cells. We found that the activity of phospholipase D isoform 2 (PLD2) is highly increased in cancers with larger size and poor prognosis (MDA-MB-231 vs. MCF-7 cells), so we determined if Snail or Slug were responsible for PLD2 gene transcription regulation. Unexpectedly, we found that PLD2 expression was positively regulated by Slug but negatively regulated by Snail. (Source: Molecular Oncology)
Source: Molecular Oncology - December 18, 2015 Category: Cancer & Oncology Authors: Ramya Ganesan, Elizabeth Mallets, Julian Gomez-Cambronero Source Type: research
Liquid Biopsy Utility for the Surveillance of Cutaneous Malignant Melanoma Patients
Cutaneous melanoma is one of the highest incident-rate cancers with increasing prevalence in Western societies. Despite the advent of new approved therapeutics, the 5-year overall survival rate of stage IV melanoma patients remains below 15%. Current treatments for late-stage disease have shown higher efficacy when treated at a lower disease burden. Thus, blood-based biomarkers capable of detecting melanoma prior to clinically evident distant metastasis, will improve the treatment and outcomes for melanoma patients. (Source: Molecular Oncology)
Source: Molecular Oncology - December 17, 2015 Category: Cancer & Oncology Authors: Sharon K. Huang, Dave S.B. Hoon Tags: Review Source Type: research
AGR2 oncoprotein inhibits p38 MAPK and p53 activation through a DUSP10-mediated regulatory pathway
The tumor suppressor p53 plays a key role in malignant transformation and tumor development. However, the frequency of p53 mutations within individual types of cancer is different, suggesting the existence of other mechanisms attenuating p53 tumor suppressor activity. Changes in upstream regulators of p53 such as MDM2 amplification and overexpression, expression of viral oncoproteins, estrogen receptor signaling, or changes in p53 transcriptional target genes were previously described in wild-type p53 tumors. (Source: Molecular Oncology)
Source: Molecular Oncology - December 16, 2015 Category: Cancer & Oncology Authors: Roman Hrstka, Pavla Bouchalova, Eva Michalova, Eva Matoulkova, Petr Muller, Philip J. Coates, Borivoj Vojtesek Source Type: research
Cell-free circulating tumour DNA as a liquid biopsy in breast cancer
Recent developments in massively parallel sequencing and digital genomic techniques support the clinical validity of cell-free circulating tumour DNA (ctDNA) as a ‘liquid biopsy’ in human cancer. In breast cancer, ctDNA detected in plasma can be used to non-invasively scan tumour genomes and quantify tumour burden. The applications for ctDNA in plasma include identifying actionable genomic alterations, monitoring treatment responses, unravelling therapeutic resistance, and potentially detecting disease progression before clinical and radiological confirmation. (Source: Molecular Oncology)
Source: Molecular Oncology - December 16, 2015 Category: Cancer & Oncology Authors: Leticia De Mattos-Arruda, Carlos Caldas Tags: Review Source Type: research
AGR2 oncoprotein inhibits p38MAPK and p53 activation through a DUSP10-mediated regulatory pathway
The tumor suppressor p53 plays a key role in malignant transformation and tumor development. However, the frequency of p53 mutations within individual types of cancer is different, suggesting the existence of other mechanisms attenuating p53 tumor suppressor activity. Changes in upstream regulators of p53 such as MDM2 amplification and overexpression, expression of viral oncoproteins, estrogen receptor signaling, or changes in p53 transcriptional target genes were previously described in wild-type p53 tumors. (Source: Molecular Oncology)
Source: Molecular Oncology - December 16, 2015 Category: Cancer & Oncology Authors: Roman Hrstka, Pavla Bouchalova, Eva Michalova, Eva Matoulkova, Petr Muller, Philip J. Coates, Borivoj Vojtesek Source Type: research
Non-invasive detection of genome-wide somatic copy number alterations by liquid biopsies
Liquid biopsies, i.e. the analysis of circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA), are evolving into promising clinical tools. Indeed, a plethora of liquid biopsy technologies to deduce non-invasively characteristics of the tumor genome from the peripheral blood have been developed over the last few years. For example, liquid biopsies have been used to assess the tumor burden, to monitor the evolution of tumor genomes, to unravel mechanisms of resistance, to establish the tumor heterogeneity, and for the identification of prognostic and predictive markers. (Source: Molecular Oncology)
Source: Molecular Oncology - December 16, 2015 Category: Cancer & Oncology Authors: Ellen Heitzer, Peter Ulz, Jochen B. Geigl, Michael R. Speicher Tags: Review Source Type: research
Blood circulating tumor DNA for non-invasive genotyping of colon cancer patients
Most solid tumors, including colorectal cancers, shed cell-free DNA (ctDNA) in the blood. ctDNA can be analyzed to generate molecular profiles which capture the heterogeneity of the disease more comprehensively then tumor tissue biopsies. This approach commonly called ‘liquid biopsy’ can be applied to monitor response to therapy, to assess minimal residual disease and to uncover the emergence of drug resistance. This review will discuss ctDNA applications in the clinical management of colorectal cancer patients and will provide perspective on future development of utilizing body. (Source: Molecular Oncology)
Source: Molecular Oncology - December 16, 2015 Category: Cancer & Oncology Authors: Giulia Siravegna, Alberto Bardelli Source Type: research
