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Lung cancer, breast cancer, mutation, biomarkers

Angelica Sonzogni, Fabrizio Bianchi, Alessandra Fabbri, Mara Cossa, Giulio Rossi, Alberto Cavazza, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Benedetta Picciani, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes...
April 2017: Journal of Pathology. Clinical Research
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignacio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
April 25, 2017: Oncotarget
Mohsin H K Roshan, Amos Tambo, Nikolai P Pace
Colorectal cancer (CRC) is the fourth commonest type of malignancy after breast, lung and prostate in the USA and accounts for approximately 49,190 deaths annually in USA alone. The 5-year survival rate of CRC has increased over the past decades, in part, due to greater awareness and the widespread implementation of national screening programmes. Recently, a number of studies reported that males have a higher risk of developing CRC due to the action of testosterone. Testosterone is an androgen that is responsible for the development of male secondary sex characteristics and for spermatogenesis...
2016: EPMA Journal
Hidehito Horinouchi
The mutation or expression of HER family members serves as a therapeutic target for tyrosine kinase inhibitors or monoclonal antibodies in diverse cancers, such as non-small cell lung cancer, breast cancer, gastric cancer, head and neck cancer, colorectal cancer, pancreatic cancer and glioblastoma. HER3, which heterodimerizes with HER1 and HER2, has received much attention as a potential target for anti-EGFR treatment. Patritumab is a novel, fully human monoclonal antibody directed against HER3. Areas covered: In this review article, an overview of the market, chemistry, pharmacodynamics, pharmacokinetics, efficacy, and safety of patritumab is provided based on data from phase I studies, a combination phase I trial, and a randomized phase II trial comparing two doses of patritumab...
December 2016: Expert Opinion on Biological Therapy
Radmila Lemstrova, Bohuslav Melichar, Beatrice Mohelnikova-Duchonova
Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival...
December 2016: Cancer Chemotherapy and Pharmacology
Matt R Paul, Nicholas P Levitt, David E Moore, Patricia M Watson, Robert C Wilson, Chadrick E Denlinger, Dennis K Watson, Paul E Anderson
BACKGROUND: It has recently been shown that significant and accurate single nucleotide variants (SNVs) can be reliably called from RNA-Seq data. These may provide another source of features for multivariate predictive modeling of disease phenotype for the prioritization of candidate biomarkers. The continuous nature of SNV allele fraction features allows the concurrent investigation of several genomic phenomena, including allele specific expression, clonal expansion and/or deletion, and copy number variation...
March 31, 2016: BMC Genomics
Sergio Alonso, Beatriz González, Tatiana Ruiz-Larroya, Mercedes Durán Domínguez, Takaharu Kato, Akihiro Matsunaga, Koichi Suzuki, Alex Y Strongin, Pepita Gimènez-Bonafé, Manuel Perucho
BACKGROUND: ADAMTS19 encodes a member of the ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) protein family with emerging roles in carcinogenesis and metastasis. ADAMTS shares several distinct protein modules including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. In a previous work, we found ADAMTS19 frequently hypermethylated in colorectal cancer (CRC). We explored the association of methylation with tumor genotype and phenotype...
2015: Clinical Epigenetics
Kathy Gately, Lydia Forde, Stephen Gray, Derek Morris, Aidan Corvin, Prerna Tewari, Kenneth O'Byrne
The insulin-like growth factor 1 receptor (IGF1R) pathway plays an important role in the pathogenesis of non-small cell lung cancer (NSCLC) and also provides a mechanism of resistance to targeted therapies. IGF1R is therefore an ideal therapeutic target and several inhibitors have entered clinical trials. However, thus far the response to these inhibitors has been poor, highlighting the importance of predictive biomarkers to identify patient cohorts who will benefit from these targeted agents. It is well-documented that mutations and/or deletions in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain predict sensitivity of NSCLC patients to EGFR TK inhibitors...
September 2015: Molecular and Clinical Oncology
Laszlo G Radvanyi
Autologous adoptive T-cell therapies have made tremendous strides over the last few years with excitement currently being generated by technologies that can reprogram T-cell specificities toward any desired antigen including chimeric antigen receptors and recombinant T-cell receptors. Time will tell whether these new genetically engineered T-cell technologies will be effective as advertised, especially in solid tumors, considering the limited availability of specific antigens and the difficulty in managing the unpredictable on-target, off-tissue toxicities...
November 2015: Cancer Journal
Dario Presutti, Simonetta Santini, Beatrice Cardinali, Giuliana Papoff, Cristiana Lalli, Simone Samperna, Valentina Fustaino, Giuseppe Giannini, Giovina Ruberti
Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer...
2015: PloS One
Hugo Gómez-Rueda, Emmanuel Martínez-Ledesma, Antonio Martínez-Torteya, Rebeca Palacios-Corona, Victor Trevino
BACKGROUND: In cancer, large-scale technologies such as next-generation sequencing and microarrays have produced a wide number of genomic features such as DNA copy number alterations (CNA), mRNA expression (EXPR), microRNA expression (MIRNA), and DNA somatic mutations (MUT), among others. Several analyses of a specific type of these genomic data have generated many prognostic biomarkers in cancer. However, it is uncertain which of these data is more powerful and whether the best data-type is cancer-type dependent...
2015: BioData Mining
N P Tobin, T Foukakis, L De Petris, J Bergh
The past 30 years have seen the introduction of a number of cancer therapies with the aim of restricting the growth and spread of primary and metastatic tumours. A shared commonality among these therapies is their targeting of various aspects of the cancer hallmarks, that is traits that are essential to successful tumour propagation and dissemination. The evolution of molecular-scale technology has been central to the identification of new cancer targets, and it is not a coincidence that improved therapies have emerged at the same time as gene expression arrays and DNA sequencing have enhanced our understanding of cancer genetics...
December 2015: Journal of Internal Medicine
Gorka Ruiz de Garibay, Carmen Herranz, Alicia Llorente, Jacopo Boni, Jordi Serra-Musach, Francesca Mateo, Helena Aguilar, Laia Gómez-Baldó, Anna Petit, August Vidal, Fina Climent, Javier Hernández-Losa, Álex Cordero, Eva González-Suárez, José Vicente Sánchez-Mut, Manel Esteller, Roger Llatjós, Mar Varela, José Ignacio López, Nadia García, Ana I Extremera, Anna Gumà, Raúl Ortega, María Jesús Plà, Adela Fernández, Sònia Pernas, Catalina Falo, Idoia Morilla, Miriam Campos, Miguel Gil, Antonio Román, María Molina-Molina, Piedad Ussetti, Rosalía Laporta, Claudia Valenzuela, Julio Ancochea, Antoni Xaubet, Álvaro Casanova, Miguel Angel Pujana
Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies...
2015: PloS One
Magdalena Uvirova, Jarmila Simova, Barbora Kubova, Nina Dvorackova, Hana Tomaskova, Monika Sedivcova, Petr Dite
AIMS: A germline SNP (rs61764370) is located in a let-7 complementary site (LCS6) in the 3'UTR of KRAS oncogene, and it was found to alter the binding capability of the mature let-7 microRNA to the KRAS mRNA. The aim of the study was to evaluate the frequency of the KRAS-LCS6 variant allele in different cancer types that included patients with colorectal cancer (CRC), breast cancer (BC), non-small cell lung cancer (NSCLC) and brain tumour patient subgroups from the Czech Republic. The occurrence of this genetic variant was correlated with the presence of selected somatic mutations representing predictive biomarkers in the respective tumours...
September 2015: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
W L Santivasi, H Wang, T Wang, Q Yang, X Mo, E Brogi, B G Haffty, A B Chakravarthy, Fen Xia
BACKGROUND: Although BRCA1 has been extensively studied for its role as a tumour-suppressor protein, the role of BRCA1 subcellular localisation in oncogenesis and tumour progression has remained unclear. This study explores the impact of BRCA1 mislocalisation on clinical outcomes in breast cancer. METHODS: Tissue microarrays assembled from a cohort of patients with all stages of breast cancer were analysed for BRCA1 localisation and correlated with patient survival...
July 28, 2015: British Journal of Cancer
Blanca D López-Ayllón, Javier de Castro-Carpeño, Carlos Rodriguez, Olga Pernía, Inmaculada Ibañez de Cáceres, Cristobal Belda-Iniesta, Rosario Perona, Leandro Sastre
Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancers, which are the leading cause of cancer-related deaths in the world. Tyrosine kinase inhibitors such as erlotinib represent one therapeutic options presently recommended for tumors produced by activating mutations in the gene coding of epidermal growth factor receptor (EGFR). The aim of this study is the identification of possible biomarkers for tumor sensitivity to erlotinib in the absence of the main EGFR mutations. The erlotinib sensitivity of cells isolated from 41 untreated NSCLC patients was determined and compared with the presence of the more frequent EGFR mutations...
2015: International Journal of Clinical and Experimental Pathology
Kristina Warton, Goli Samimi
A range of molecular alterations found in tumor cells, such as DNA mutations and DNA methylation, is reflected in cell-free circulating DNA (circDNA) released from the tumor into the blood, thereby making circDNA an ideal candidate for the basis of a blood-based cancer diagnosis test. In many cancer types, mutations driving tumor development and progression are present in a wide range of oncogenes and tumor suppressor genes. However, even when a gene is consistently mutated in a particular cancer, the mutations can be spread over very large regions of its sequence, making evaluation difficult...
2015: Frontiers in Molecular Biosciences
Eric Dansin, Aurélien Carnot, Véronique Servent, Dorothée Daussay, Yves-Marie Robin, Ecaterina Surmei-Pintilie, Géraldine Lauridant, Clothilde Descarpentries, Françoise Révillion, Claire Delattre
Breast metastasis from other primary carcinoma is very rare and could be difficult to identify despite immunohistochemistry analysis. Breast metastasis from lung adenocarcinoma can mimic triple-negative breast cancer. Given the prognosis and therapeutic challenges, a correct diagnosis appears essential, and molecular biomarkers could be useful. We report the case of a 52-year-old woman with a breast mass initially diagnosed as primary breast cancer and secondarily attached to breast metastasis from an EGFR-mutated lung adenocarcinoma...
January 2015: Case Reports in Oncology
Shingo Kamoshida
The availability of companion biomarkers should improve chemotherapeutic effectiveness, decrease ad- verse effects, and lead to individualized cancer treatment. In this article, the role of immunohistochemistry (IHC) in detecting companion biomarkers is reviewed. The hormone receptor (HR) is a companion bi- omarker for hormonal therapy in breast cancers, and IHC is the standard assay for detecting HR expression. The overexpression/amplification of human epidermal growth factor receptor 2 (HER2) is predictive of a favorable response to anti-HER2 agents such as trastuzumab, lapatinib, and pertuzumab...
July 2014: Rinsho Byori. the Japanese Journal of Clinical Pathology
Jing Song, Yenji Shen, Jing Zhang, Qingquan Lian
BACKGROUND: Propofol (2, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent administered to induce and maintain anesthesia. It has been recently revealed that propofol has anticancer properties including direct and indirect suppression of the viability and proliferation of cancer cells by promoting apoptosis in some cancer cell lines. METHODOLOGY/PRINCIPAL FINDINGS: This study aimed to establish a profile to quantitatively and functionally evaluate the anticancer properties of propofol in three cancer cell lines: non-small cell lung carcinoma cell line A549, human colon carcinoma cell line LoVo, and human breast cancer cell line SK-BR-3...
2014: PloS One
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