Search Our Scientific Publications & Authors

HPB (Oxford) 2019 Feb 11. Epub 2019 Feb 11.

Department of Surgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Background: Associated liver partition and portal vein ligation in staged hepatectomy (ALPPS) is an alternative resection method to portal vein embolization (PVE) in patients with small future liver remnants (FLR) but has been associated with early tumor recurrences.

Methods: Twenty-four patients with colorectal liver metastases (CRLM) patients from the randomized multicenter LIGRO trial comparing outcome of ALPPS (n = 13) vs PVE (n = 11) were included in the study. Mutational analyses of the KRAS, NRAS, BRAF, PIC3CA and TP53 genes of the metastases were performed in 21 patients and correlated to early tumor recurrence. Read More

Cell Death Dis 2019 Feb 13;10(2):143. Epub 2019 Feb 13.

LIM 64, Instituto do Coracao (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Protein disulfide isomerases including PDIA1 are implicated in cancer progression, but underlying mechanisms are unclear. PDIA1 is known to support vascular Nox1 NADPH oxidase expression/activation. Since deregulated reactive oxygen species (ROS) production underlies tumor growth, we proposed that PDIA1 is an upstream regulator of tumor-associated ROS. Read More

Ann Ital Chir 2019 Feb 4;8. Epub 2019 Feb 4.

Background: Colorectal cancer (CRC) is one of the leading cause of cancer deaths worldwide. The aetiology of CRC is complex and involves interaction on environmental and genetic factors. The two most important pathways are the EGFR (Epidermal Grow Factor Receptor) signaling pathway, with the involvement of KRAS and BRAF, and the DNA mismatch repair (MMR). Read More

BMJ Case Rep 2019 Feb 9;12(2). Epub 2019 Feb 9.

Department of Hematology/Oncology, Presence Saint Joseph Hospital Chicago, Chicago, Illinois, USA.

Panitumumab is a recombinant human IgG monoclonal antibody which is used for the treatment of patients with metastatic colorectal cancer (mCRC) with disease progression on or following FOLFIRI (fluoropyrimidine, oxaliplatin and irinotecan) containing chemotherapy regimen. We report a case of an 83-year-old Hispanic man, non-smoker, with KRAS/NRAS wild-type mCRC of the liver who was treated with 9 cycles of FOLFOX4 (fluorouracil, leucovorin and oxaliplatin) and cetuximab. Follow-up abdominal imaging showed progression of CRC, requiring initiation of panitumumab in addition to FOLFIRI. Read More

Pathol Res Pract 2019 Feb 3. Epub 2019 Feb 3.

Department of Medicine (DIMED), Surgical Pathology Unit, University of Padua, Padua, 35121, Italy.

Colorectal cancer (CRC) is a heterogeneous group of diseases both from the morphological and molecular point of view. The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations. However, no study so far investigated the molecular landscape of "sessile serrated" adenoma to carcinoma transition in early CRCs. Read More

J Surg Res 2019 Feb 5. Epub 2019 Feb 5.

Division of Surgical Oncology, National Cancer Centre, Singapore. Electronic address:

Background: Mutant KRAS tumors are purported to metastasize differently than wild-type KRAS tumors. The biological heterogeneity of tumors from different parts of the colon are also reported to affect metastasis. This study aims to characterize the metastatic profile by evaluating these factors in unison. Read More

J Pers Med 2019 Feb 7;9(1). Epub 2019 Feb 7.

Medical School, University of Ioannina, Stavros Niarchou Avenue, 45110 Ioannina, Greece.

Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Read More

EBioMedicine 2019 Feb 4. Epub 2019 Feb 4.

Colorectal & Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK; Division of Cancer Sciences, School of Medical Science, Faculty of Biology, Medicine and Health, University of Manchester, UK. Electronic address:

Background: The use of biomarkers to target anti-EGFR treatments for metastatic colorectal cancer (CRC) is well-established, requiring molecular analysis of primary or metastatic biopsies. We aim to review concordance between primary CRC and its metastatic sites.

Methods: A systematic review and meta-analysis of all published studies (1991-2018) reporting on biomarker concordance between primary CRC and its metastatic site(s) was undertaken according to PRISMA guidelines using several medical databases. Read More

PLoS One 2019 7;14(2):e0212142. Epub 2019 Feb 7.

Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.

The SMAD4 tumor suppressor gene product inhibits transforming growth factor-β-mediated signaling and is mutated in ~10% of colorectal carcinomas. The prognostic significance of SMAD4 mutations has been controversial. We studied the pathological and clinical characteristics of SMAD4-mutated intestinal adenocarcinomas using a retrospective case-control study design. Read More

Clin Med Insights Oncol 2019 30;13:1179554918825447. Epub 2019 Jan 30.

Medical Oncology Section, The Oncology Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

Background: Regorafenib is a multi-kinase inhibitor approved for treatment of refractory advanced colorectal cancer. It was found in the clinical trials to have a modest benefit and significant toxicity. Our aim was to assess the outcome in our local clinic practice. Read More

Cancer Sci 2019 Feb 6. Epub 2019 Feb 6.

Department of Cell Biology, The Cancer Institute, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo, 135-8550, Japan.

Colorectal cancer (CRC) is caused by genetic alterations, and comprehensive sequence analyses have revealed the mutation landscapes. In addition to somatic changes, genetic variations are considered important factors contributing to tumor development; however, our knowledge on this subject is limited. Familial adenomatous polyposis coli (FAP) is an autosomal-dominant inherited disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. Read More

Mod Pathol 2019 Feb 5. Epub 2019 Feb 5.

Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, and Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Oncogenic fusions are rare in colorectal carcinomas, but may be important for prognosis and therapy. An effective strategy for screening targetable oncogenic fusions in colorectal carcinomas is needed. Here, we investigate molecular genetic alterations in colorectal carcinomas based on their DNA mismatch repair status, and to effectively screen for targetable oncogenic fusions in colorectal carcinomas. Read More

Mod Pathol 2019 Feb 5. Epub 2019 Feb 5.

Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

Pulmonary enteric adenocarcinoma is a rare non-small cell lung cancer subtype. It is poorly characterized and cannot be distinguished from metastatic colorectal or upper gastrointestinal adenocarcinomas by means of routine pathological methods. As DNA methylation patterns are known to be highly tissue specific, we aimed to develop a methylation-based algorithm to differentiate these entities. Read More

Saudi J Gastroenterol 2019 Feb 1. Epub 2019 Feb 1.

Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Guangzhou, China.

Background/aim: To construct quantitative prognostic models for colorectal cancer (CRC) based on COX-2/C-MET/KRAS expression status in clinical practice.

Patients And Methods: Clinical factors and COX-2/C-MET/KRAS expression status of 578 eligible patients from two Chinese hospitals were included. The patients were randomly allocated into training and validation datasets. Read More

FEBS J 2019 Feb 4. Epub 2019 Feb 4.

Laboratory for Systems Biology and Bio-inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), is being widely used for colorectal cancer (CRC) with wild-type KRAS. However, its responsiveness is still very limited and wild-type KRAS is not enough to indicate such responsiveness. Here, by analyzing the gene expression data of CRC patients treated with cetuximab monotherapy, we have identified DUSP4, ETV5, GNB5, NT5E, and PHLDA1 as potential targets to overcome cetuximab resistance. Read More

Cancers (Basel) 2019 Feb 1;11(2). Epub 2019 Feb 1.

Unit for Cell Signaling, Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0372 Oslo, Norway.

The majority of colorectal cancers are induced by subsequent mutations in and genes leading to aberrant activation of both canonical WNT and RAS signaling. However, due to induction of feedback rescue mechanisms some cancers do not respond well to targeted inhibitor treatments. In this study we show that the and mutant human colorectal cancer cell line HCT-15 induces canonical WNT signaling through YAP in a MEK dependent mechanism. Read More

Proc Natl Acad Sci U S A 2019 Feb 1. Epub 2019 Feb 1.

Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892;

Oncogenic mutations in the small GTPase KRAS are frequently found in human cancers, and, currently, there are no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed a panel of mutant colorectal and pancreatic cancer cell lines for their dependency on 28 gene nodes that represent canonical RAS effector pathways and selected stress response pathways. We found that RAF node knockdown best differentiated mutant and WT cancer cells, suggesting RAF kinases are key oncoeffectors for addiction. Read More

Front Oncol 2018 17;8:652. Epub 2019 Jan 17.

Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States.

Liquid biopsy (LB) captures dynamic genomic alterations (alts) across metastatic colorectal cancer (mCRC) therapy and may complement tissue biopsy (TB). We sought to describe the utility of LB and better understand mCRC biology during therapy. Thirty-three patients (pts) with mCRC underwent LB. Read More

Mol Carcinog 2019 Jan 29. Epub 2019 Jan 29.

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Life Sciences, Northwest University, Xi'an, 710069, China.

Sporadic colorectal cancer (sCRC) is one of the leading causes of cancer death worldwide. As a highly heterogeneous complex disease, the currently reported classical genetic markers for sCRC, including APC, KRAS, BRAF and TP53 gene mutations and epigenetic alterations, can explain only some sCRC patients. Here, we first reported a deleterious c. Read More

Clin Cancer Res 2019 Jan 28. Epub 2019 Jan 28.

Division of Medical Oncology, Norris Comprehensive Cancer Center, University of Southern California.

Purpose: The natural history and prognosis of appendiceal adenocarcinomas (AA) differ from those of adenocarcinomas arising in other large bowel sites. We aimed to compare the molecular profiles exhibited by AAs and CRCs, or between the histopathological subtypes of AA.

Experimental Design: A total of 183 samples from AA (46 adenocarcinoma, not otherwise specified (NOS), 66 pseudomyxoma peritonei (PMP), 44 mucinous adenocarcinoma (MU), and 27 signet ring cell carcinoma (SR)), 994 from right-sided colorectal cancer (R-CRC), and 1080 from left-sided CRC (L-CRC) were analyzed by next-generation sequencing (NGS) and immunohistochemical (IHC) markers. Read More

J Exp Clin Cancer Res 2019 Jan 28;38(1):41. Epub 2019 Jan 28.

Department of Precision Medicine, Università degli studi della Campania "Luigi Vanvitelli", 80131, Naples, Italy.

Background: Previous studies showed that the combination of an anti-Epidermal growth factor (EGFR) and a MEK-inhibitor is able to prevent the onset of resistance to anti-EGFR monoclonal antibodies in KRAS-wild type colorectal cancer (CRC), while the same combination reverts anti-EGFR primary resistance in KRAS mutated CRC cell lines. However, rapid onset of resistance is a limit to combination therapies in KRAS mutated CRC.

Methods: We generated four different KRAS mutated CRC cell lines resistant to a combination of cetuximab (an anti-EGFR antibody) and refametinib (a selective MEK-inhibitor) after continuous exposure to increasing concentration of the drugs. Read More

Ann Oncol 2019 Jan 23. Epub 2019 Jan 23.

Medical Oncology Department, Hospital del Mar-IMIM, CIBERONC Instituto de Salud Carlos III, Barcelona, Spain.

Background: Extended RAS analysis is mandatory in metastatic colorectal cancer (mCRC) patients. The optimal threshold of RAS mutated subclones to identify patients most likely to benefit from anti-EGFR therapy is controversial. Our aim was to assess the clinical impact of detecting mutations in RAS, BRAF, PIK3CA and EGFRS492R in basal tissue tumour samples by using a highly sensitive Next Generation Sequencing (NGS) technology in mCRC patients treated with chemotherapy plus anti-EGFR or anti-VEGF. Read More

Nat Commun 2019 01 25;10(1):449. Epub 2019 Jan 25.

Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

T cells targeting shared oncogenic mutations can induce durable tumor regression in epithelial cancer patients. Such T cells can be detected in tumor infiltrating lymphocytes, but whether such cells can be detected in the peripheral blood of patients with the common metastatic epithelial cancer patients is unknown. Using a highly sensitive in vitro stimulation and cell enrichment of peripheral memory T cells from six metastatic cancer patients, we identified and isolated CD4, and CD8 memory T cells targeting the mutated KRAS and KRAS variants, respectively, in three patients. Read More

BMC Gastroenterol 2019 Jan 25;19(1):17. Epub 2019 Jan 25.

Emergency Department, The First Affiliated Hospital, Sun Yat-sen University, Huangpu East Road No. 183, Huangpu District, Guangzhou, 510700, China.

Background: Capecitabine plus bevacizumab (CAP-B) maintenance treatment after 6 cycles of capecitabine, oxaliplatin, and bevacizumab (CAPOXB) has demonstrated clinical activity and failure to compromise quality of life in patients with metastatic colorectal cancer (MCC) in a previous phase 3 CAIRO3 study. The objective of this study is to evaluate the efficacy and safety of CAP-B versus CAP in maintenance treatment after 6-cycle CAPOXB induction therapy in Chinese postmenopausal women with untreated characterised KRAS exon 2 wild-type MCC.

Methods: During 2012-2016, prospectively maintained databases were reviewed to evaluate cohorts with untreated characterised KRAS exon 2 wild-type MCC and stable disease or better after 6-cycle CAPOXB induction treatment. Read More

Sci Rep 2019 Jan 24;9(1):648. Epub 2019 Jan 24.

Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.

The epidermal growth factor receptor (EGFR) inhibitors such as erlotinib and gefitinib are widely used for treatment of non-small cell lung cancer (NSCLC), but they have shown limited efficacy in an unselected population of patients. The KRAS mutations, which are identified in approximately 20% of NSCLC patients, have shown to be associated with the resistance to the EGFR tyrosine kinase inhibitors (TKIs). Currently, there is no clinically available targeted therapy which can effectively inhibit NSCLC tumors harboring KRAS mutations. Read More

Int J Hyperthermia 2019 Jan 21:1-9. Epub 2019 Jan 21.

a Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) , Peking University Cancer Hospital and Institute , Beijing , China.

Purpose: We investigated the relationships between KRAS gene status and local tumor progression (LTP) of colorectal liver metastases (CLMs) after treatment with percutaneous ultrasound-guided radiofrequency ablation (RFA).

Materials And Methods: Clinical and imaging data from 76 patients (154 lesions) with CLM who underwent percutaneous ultrasound-guided RFA and had KRAS gene test results between January 2012 and June 2016 were analyzed. The average lesion size was 2. Read More

Clin Exp Med 2019 Jan 19. Epub 2019 Jan 19.

Division of Oncology, Biomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Mala Hora 4C, 03601, Martin, Slovakia.

The proto-oncogene KRAS belongs among the most frequently mutated genes in all types of cancer and is also very important oncogene related to colorectal tumors. The detection of mutations in this gene in primary tumor is a predictive biomarker for the anti-EGFR therapy in metastatic CRC (mCRC); however, the patients with wild-type KRAS can also show resistance to the personalized medicine. The droplet-based digital PCR technology has improved the analytical sensitivity of the mutations detection, which led us to the idea about the optimization of this approach for KRAS testing. Read More

BMC Surg 2019 Jan 18;19(1). Epub 2019 Jan 18.

Department of Surgery, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 8300011, Japan.

Background: Liver is a common location of colorectal metastasis, but intrabiliary growth of liver metastasis is not well recognized. Furthermore, intrabiliary metastasis that discovered over 10 years after excision has rarely been described.

Case Presentation: An 80-year-old man was admitted due to the presence of a liver mass in segment 5 (S5) concomitant with elevated carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9. Read More

J Clin Med 2019 Jan 17;8(1). Epub 2019 Jan 17.

Division of Computer Science, Sookmyung Women's University, Seoul 04310, Korea.

Background: We investigated the associations between v-Raf murine sarcoma viral oncogene homolog B1 (, henceforth ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ) mutations and colorectal cancer (CRC) prognosis, using The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GSE39582) datasets.

Materials And Methods: The effects of and mutations on overall survival (OS) and disease-free survival (DFS) of CRC were evaluated.

Results: The mutational status of and genes was not associated with overall survival (OS) or DFS of the CRC patients drawn from the TCGA database. Read More

Oncol Lett 2019 Jan 23;17(1):332-338. Epub 2018 Oct 23.

Center of Scientific Research, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

Correlation between RAS gene mutation and microsatellite instability (MSI) status in cancer tissues and clinicopathological parameters of patients with stage III colorectal cancer (CRC) were investigated. Tissues were collected from 180 patients diagnosed with stage III CRC in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from 2012 to 2016. RAS gene mutations in paraffin sections were detected by PCR and Sanger sequencing. Read More

Sci Rep 2019 Jan 17;9(1):201. Epub 2019 Jan 17.

CRUK Gene Function Laboratory and Breast Cancer Now Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, London, SW3 6JB, UK.

Inhibition of the PARP superfamily tankyrase enzymes suppresses Wnt/β-catenin signalling in tumour cells. Here, we describe here a novel, drug-like small molecule inhibitor of tankyrase MSC2504877 that inhibits the growth of APC mutant colorectal tumour cells. Parallel siRNA and drug sensitivity screens showed that the clinical CDK4/6 inhibitor palbociclib, causes enhanced sensitivity to MSC2504877. Read More

Cancer Manag Res 2019 28;11:359-368. Epub 2018 Dec 28.

Department of Oncology, Palacky University Medical School and Teaching Hospital, 775 20 Olomouc, Czech Republic.

Purpose: Although inhibitors of vascular endothelial growth factor and inhibitors of epidermal growth factor receptor (EGFRi) are commonly used for the treatment of metastatic colorectal cancer (mCRC), the optimal sequencing of these agents is currently unclear.

Methods: A national registry of targeted therapies was used to analyze baseline characteristics and outcomes of patients with mCRC and wild-type exon 2 status who received bevacizumab and EGFRi (cetuximab or panitumumab) as a part of first- and second-line treatment in either sequence.

Results: The cohort included 490 patients (181 patients treated with first-line EGFRi and second-line bevacizumab and 309 patients treated with first-line bevacizumab and second-line EGFRi). Read More

Mod Pathol 2019 Jan 14. Epub 2019 Jan 14.

Department of Pathology, Biological Sciences Institute, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil.

Adenomatoid odontogenic tumor is a benign encapsulated epithelial odontogenic tumor that shows an indolent clinical behavior. We have reported in a few adenomatoid odontogenic tumors mutations in KRAS, which is a proto-oncogene frequently mutated in cancer such as lung, pancreas, and colorectal adenocarcinomas. We aimed to assess KRAS mutations in the hotspot codons 12, 13, and 61 in a large cohort of adenomatoid odontogenic tumors and to test the association of these mutations with clinical (age, site, tumor size, follicular/extrafollicular subtypes) and histopathological parameters. Read More

Cancer Res 2019 Jan 14. Epub 2019 Jan 14.

Department of Pathology, Memorial Sloan Kettering Cancer Center

Kinase fusions are rare and poorly characterized in colorectal carcinoma (CRC), yet they present unique opportunities for targeted therapy. In this study, we characterized kinase fusions from patients with advanced CRC who had MSK-IMPACT testing of their tumors between January 2014 and June 2018. Patients were analyzed for the presence of fusions, microsatellite instability (MSI), and RAS/BRAF mutations. Read More

J Gastrointest Cancer 2019 Jan 12. Epub 2019 Jan 12.

Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Erabi Ave, P.O. Box 1985717413, Tehran, Velenjak, Iran.

Purpose: To evaluate the prognostic role of BRAF and KRAS mutations after adjustment for microsatellite instability (MSI) in Iranian colorectal cancer (CRC) patients.

Methods: BRAF and KRAS mutations and MSI status were assessed in 258 Iranian subjects with CRC. Two hundred fifty-eight consecutive stages I-IV CRC patients, who underwent surgical resection of adenocarcinoma from 2012 to 2016, were enrolled in the research. Read More

J Thorac Cardiovasc Surg 2018 Nov 26. Epub 2018 Nov 26.

Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex. Electronic address:

Objective: During resection of pulmonary metastases, the need to spare lung parenchyma is often weighed against the increased risk of local recurrence if an inadequate surgical margin is obtained. We sought to identify risk factors for local recurrence after wedge resection of pulmonary metastases of a colorectal origin.

Methods: A retrospective study of patients who underwent a wedge resection for colorectal pulmonary metastases from 2006 to 2016 was performed. Read More

Int J Cancer 2019 Jan 8. Epub 2019 Jan 8.

Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Marine omega-3 polyunsaturated fatty acids (MO3PUFAs) have anticancer properties and may improve colon cancer survival. However, it remains unknown whether the benefit differs by tumor molecular subtype. We examined data from a phase III randomized trial of FOLFOX or FOLFOX + cetuximab among 1,735 stage III colon cancer patients who completed a dietary questionnaire at enrollment. Read More

Adv Exp Med Biol 2018 ;1110:133-147

Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.

Drug resistance is a serious impediment to the treatment of cancer. The use of anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapies in patients with metastatic colorectal cancer is guided by the presence of activating point mutations in KRAS and NRAS genes in the primary tumour. However, RAS wild-type status is still not sufficient to guarantee response to cetuximab and panitumumab, with response rates limited to 70% for combinations with multidrug chemotherapy. Read More

Adv Exp Med Biol 2018 ;1110:35-53

Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.

Colorectal cancer (CRC) remains one of the leading causes of cancer mortality worldwide. Regarded as a heterogeneous disease, a number of biomarkers have been proposed to help in the stratification of CRC patients and to enable the selection of the best therapy for each patient towards personalized therapy. However, although the molecular mechanisms underlying the development of CRC have been elucidated, the therapeutic strategies available for these patients are still quite limited. Read More

J Thorac Dis 2018 Nov;10(11):6147-6157

Division of Thoracic Surgery, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.

Background: Pulmonary metastasectomy is one of the cornerstones in the treatment of oligometastatic colorectal cancer (CRC). However, the selection of patients who benefit from a surgical resection is difficult. Mutational profiling has become an essential part of diagnosis and treatment of malignant disease. Read More

Int J Cancer 2019 Jan 7. Epub 2019 Jan 7.

Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.

Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. Read More

Pathol Oncol Res 2019 Jan 5. Epub 2019 Jan 5.

2nd Department of Pathology, Semmelweis University, 93 Üllöi str, Budapest, 1091, Hungary.

Right- and left-sided colorectal cancers (RSCRC and LSCRC, respectively) are different developmentally, genetically and prognostically. Clinical data also indicate that they respond differently to anti-EGFR therapies. The role of EGFR protein expression in KRAS wild type colorectal cancer is also controversial. Read More

Int J Clin Oncol 2019 Feb 5;24(2):141-152. Epub 2019 Jan 5.

Department of Colorectal Surgery, Changhai Hospital, 168 Changhai Road, Shanghai, 200433, China.

Background: Simultaneous detection of multiple molecular biomarkers is helpful in the prediction of treatment response and prognosis for colorectal cancer (CRC) patients.

Methods: A 22-gene panel consisting of 103 hotspot regions was utilized in the formalin-fixed paraffin-embedded (FFPE) tissue samples of 207 CRC patients, using the next-generation sequencing (NGS)-based multiplex PCR technique. Those 22 genes included AKT1, ALK, BRAF, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, KRAS, MAP2K1, MET, NOTCH1, NRAS, PIK3CA, PTEN, SMAD4, STK11, and TP53. Read More

Pathol Res Pract 2018 Dec 31. Epub 2018 Dec 31.

Medical Oncology, Beijing, 100021, China. Electronic address:

Background: Characterization of genetic alterations has been revealed to be important to predict the outcomes of targeted therapy in cancer. We here aimed to assess the mutation profiling of 526 colorectal cancer (CRC) patients by next-generation sequencing (NGS) to enable a more personalized anti-EGFR treatment.

Methods: Tumors were analyzed using NGS to determine hotspot mutations in 22 cancer-related genes. Read More

Abdom Radiol (NY) 2019 Jan 2. Epub 2019 Jan 2.

Department of Nuclear Medicine, Pusan National University Hospital, Busan, South Korea.

Objective: The purpose of the current study was to investigate the diagnostic performance of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for the prediction of v-Ki-ras-2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation in colorectal cancer (CRC) patients through a systematic review and meta-analysis.

Methods: The PubMed and EMBASE database, from the earliest available date of indexing through April 30, 2018, were searched for studies evaluating the diagnostic performance of F-18 FDG PET/CT for prediction of KRAS mutation in CRC patients.

Results: Across 9 studies (804 patients), the pooled sensitivity for F-18 FDG PET/CT was 0. Read More

Oncologist 2019 Jan 2. Epub 2019 Jan 2.

Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico Universitario San Carlos, Centro de Investigación Biomédica en Red de Cancer (CIBERONC), Madrid, Spain.

Sinonasal intestinal-type adenocarcinomas (SNS-ITAC) are very rare tumors that resemble colorectal cancer in many of their pathological and molecular characteristics. Indeed, in most published series, 10%-14% of SNS-ITAC harbor mutations in . There is no standard systemic treatment in recurrent or metastatic SNS-ITAC, and there is no evidence of the use of any targeted agent in this entity. Read More

World J Gastroenterol 2018 Dec;24(47):5351-5365

Department of Biology, UNESP, Univ. Estadual Paulista, Campus of São José do Rio Preto, São José do Rio Preto, São Paulo 15054-000, Brazil.

Aim: To examine the effect of () on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs (miRNAs).

Methods: Levels of DNA, cytokine gene mRNA (, , , , , and ), and potentially interacting miRNAs (miR-21-3p, miR-22-3p, miR-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction (qPCR) TaqMan assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma (CRA) and 43 colorectal cancer (CRC) patients. mutations were detected by direct sequencing and microsatellite instability (MSI) status by multiplex PCR. Read More

Clin Colorectal Cancer 2018 Nov 28. Epub 2018 Nov 28.

Canadian Cancer Trials Group, Kingston, Canada.

Background: The safety and efficacy of targeted therapy in older patients (≥ 70 years) with metastatic colorectal cancer is not well evaluated.

Patients And Methods: Outcomes of older patients (including overall survival [OS], progression-free survival [PFS], toxicity, and quality of life [QoL]) were compared to young patients using data from 2 large previously reported clinical trials, CO.17 (cetuximab vs. Read More

Transl Oncol 2019 Mar 27;12(3):502-512. Epub 2018 Dec 27.

Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Biomarkers and Biotech Drugs, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address:

Background: To evaluate the efficacy and toxicities of regorafenib plus irinotecan, dose-escalated on the basis of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotyping, in previously heavily treated metastatic colorectal cancer (mCRC) and the prognostic values of EGFR expression, KRAS mutations, and tumor sidedness.

Methods: Forty-one patients with mCRC with disease progression after treatment with fluoropyrimidines, oxaliplatin, irinotecan, anti-VEGF, and anti-EGFR MoAbs were subjected to UGT1A1 genotyping and received regorafenib combined with FOLFIRI with dose-escalated irinotecan.

Results: The median follow-up period was 10. Read More

Cell Chem Biol 2018 Dec 5. Epub 2018 Dec 5.

Department of Molecular Medicine, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA; Irell and Manella Graduate School of Biological Sciences of City of Hope, Duarte, CA, USA. Electronic address:

Ubiquitin-like (Ubl) post-translational modifications are potential targets for therapeutics. However, the only known mechanism for inhibiting a Ubl-activating enzyme is through targeting its ATP-binding site. Here we identify an allosteric inhibitory site in the small ubiquitin-like modifier (SUMO)-activating enzyme (E1). Read More