4,287 results match your criteria Colorectal Cancer and KRAS


Intrahepatic Oxaliplatin and Systemic 5-FU +/- Cetuximab in Chemo-Naïve Patients with Liver Metastases from Colorectal Cancer.

Oncology 2019 Apr 18. Epub 2019 Apr 18.

Department of Oncology, Copenhagen University Hospital, Herlev and Gentofte, Herlev, Denmark.

Background: In case of response to chemotherapy, unresectable liver metastases from colorectal cancer can be converted to resectable and thereby obtain a chance of cure. The primary aim of this trial was to evaluate the response rate with intrahepatic oxaliplatin in combination with systemic 5-FU +/- cetuximab. Secondary aims were to evaluate the conversion rate from unresectable to resectable liver metastases, median progression-free survival, median overall survival, and toxicity. Read More

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http://dx.doi.org/10.1159/000499314DOI Listing
April 2019
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Altered miR-21, miRNA-148a Expression in Relation to KRAS Mutation Status as Indicator of Adenoma-Carcinoma Transitional Pattern in Colorectal Adenoma and Carcinoma Lesions.

Biochem Genet 2019 Apr 17. Epub 2019 Apr 17.

Colorectal Cancer Research Center and Department of Biochemistry, Shiraz University of Medical Sciences, P.O Box 1167, Shiraz, Iran.

Sporadic colorectal cancer (CRC) is a fatal disease, mostly known as the silent killer, due to the fact that this disease is asymptomatic before diagnosis in advanced stage. Screening and the early detection of CRC and colorectal adenoma (CRA) by non-aggressive molecular biomarkers' signature is useful for improvement of survival rate in CRC patients. To achieve such a goal, a better understanding of distinct molecular abnormalities as candidate biomarkers in CRC development is crucial. Read More

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http://dx.doi.org/10.1007/s10528-019-09918-0DOI Listing
April 2019
1 Read

Oncogenic KRAS Drives Immune Suppression in Colorectal Cancer.

Cancer Cell 2019 Apr;35(4):535-537

Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA; Department of Breast Oncology, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA. Electronic address:

In this issue of Cancer Cell, Liao et al. demonstrate that oncogenic KRAS drives an immune suppressive program in colorectal cancer by repressing IRF2 expression, which leads to downregulation of interferon responsive genes, enhanced expression of CXCL3 and recruitment of suppressive myeloid cells, and subsequent resistance to immune checkpoint blockade. Read More

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http://dx.doi.org/10.1016/j.ccell.2019.03.008DOI Listing
April 2019
1 Read

Survival and prognostic factors in surgically treated brain metastases.

J Neurooncol 2019 Apr 16. Epub 2019 Apr 16.

Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham and Women's Hospital, 60 Fenwood Rd., 4th Floor, Boston, MA, 02115, USA.

Purpose: While surgery and radiation remain the mainstays of therapy for all patients with brain metastases (BM), the management is moving to a more individualized approach based on the underlying tumor. We sought to identify prognostic factors of both intracranial progression (IC-PFS) and overall survival (OS) in a surgical cohort.

Methods: We retrospectively reviewed the records of 1015 patients treated surgically for BM at Brigham and Women's Hospital (2007-2017). Read More

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http://link.springer.com/10.1007/s11060-019-03171-6
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http://dx.doi.org/10.1007/s11060-019-03171-6DOI Listing
April 2019
2 Reads

Selecting treatment options in refractory metastatic colorectal cancer.

Onco Targets Ther 2019 27;12:2271-2278. Epub 2019 Mar 27.

Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra, Lake Success, NY, USA,

Survival of patients with metastatic colorectal cancer (mCRC) has significantly improved in the last decade. Survival gains are not driven by advances in first-line therapy but by incremental additional effects of subsequent treatment lines. To maximize outcomes, patients should receive all active agents. Read More

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http://dx.doi.org/10.2147/OTT.S194605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441549PMC
March 2019
1 Read

Anti-MEK and Anti-EGFR mAbs in RAS-Mutant Metastatic Colorectal Cancer: Case Series and Rationale.

Adv Ther 2019 Apr 12. Epub 2019 Apr 12.

Platform of Transfer in Cancer Biology, Centre Georges-François Leclerc, 21000, Dijon, France.

KRAS (Kirsten rat sarcoma viral oncogene) or BRAF (v-raf murine sarcoma viral oncogene homolog B1) constitutive activation leads to anti-EGFR (epidermal growth factor receptor) therapy resistance of metastatic colorectal cancer patients. In this article we investigate the effects of anti-MEK (mitogen-activated protein kinase) antibody (trametinib) combined with anti-EGFR (cetuximab) on colon cancer cell lines with different RAS statuses. Even though cetuximab has no effect on RAS cell viability and ERK (extracellular-signal-regulated kinase) phosphorylation (one of the last kinases of the EGFR pathway), trametinib can induce cell death and inhibit the activation of ERK alone or in combination with cetuximab. Read More

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http://link.springer.com/10.1007/s12325-019-00949-y
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http://dx.doi.org/10.1007/s12325-019-00949-yDOI Listing
April 2019
4 Reads

KRAS mutational status impacts pathologic response to pre-hepatectomy chemotherapy: a study from the International Genetic Consortium for Liver Metastases.

HPB (Oxford) 2019 Apr 9. Epub 2019 Apr 9.

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address:

Background: A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined.

Methods: Pathologic response was characterized as minor or major depending on the percentage of remnant viable cells (>50% vs <50%, respectively). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S1365182X193049
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http://dx.doi.org/10.1016/j.hpb.2019.03.368DOI Listing
April 2019
3 Reads

Detection of KRAS mutation via ligation-initiated LAMP reaction.

Sci Rep 2019 Apr 11;9(1):5955. Epub 2019 Apr 11.

Department of Laboratory Medicine, The Affiliated Hospital of Zunyi Medical University, Zunyi, 563003, P.R. China.

KRAS mutations are abnormalities widely found in genomic DNA and circulating tumor DNA (ctDNA) of various types of cancers. Thus, highly sensitive detection of KRAS mutations in genomic DNA is of great significance in disease diagnosis and personalized medicine. Here, we developed a ligation-initiated loop-mediated isothermal amplification (LAMP) assaying method for ultrasensitive detection of KRAS mutation. Read More

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http://www.nature.com/articles/s41598-019-42542-x
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http://dx.doi.org/10.1038/s41598-019-42542-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459849PMC
April 2019
5 Reads

Circulating Tumor DNA Detection in the Management of Anti-EGFR Therapy for Advanced Colorectal Cancer.

Front Oncol 2019 22;9:170. Epub 2019 Mar 22.

Sociedade Beneficente de Senhoras-Hospital Sírio Libanês, São Paulo, Brazil.

Anti-EGFR antibodies are a standard care for advanced -wild type colorectal cancers. Circulating tumor DNA (ctDNA) monitoring during therapy can detect emergence of mutant clones and early resistance to therapy. We describe a 61-years-old man presenting a metastatic and recurrent rectal cancer treated with different chemotherapy regimens. Read More

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http://dx.doi.org/10.3389/fonc.2019.00170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439419PMC

Role of miRNA in transformation from normal tissue to colorectal adenoma and cancer.

J Cancer Res Ther 2019 ;15(2):278-285

Department of Gastroenterology, The Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China.

Although many modalities can be used to prolong the remission of colorectal cancer (CRC), early diagnosis is essential to improve the therapeutic outcomes. The conventional ways of diagnosing and monitoring the progresses from adenoma to CRC are colonoscopy and fecal occult blood test (FOBT). However, colonoscopy is expensive and invasive; while the FOBT is not sensitive. Read More

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http://dx.doi.org/10.4103/jcrt.JCRT_135_18DOI Listing
January 2019
1 Read

Non-V600E BRAF mutations and EGFR signaling pathway in colorectal cancer.

Int J Cancer 2019 Apr 9. Epub 2019 Apr 9.

Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

The BRAF mutation (MT) in metastatic colorectal cancer (CRC) is a well-known prognostic indicator and a negative predictive biomarker for anti-epidermal growth factor receptor (EGFR) treatment. However, the clinical characteristics and significance of BRAF MTs remain unclear. Here, we evaluated the clinical characteristics of BRAF MTs versus those of other MTs in the EGFR signaling pathway, including BRAF . Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32320
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http://dx.doi.org/10.1002/ijc.32320DOI Listing
April 2019
4 Reads

Calcium intake and colon cancer risk subtypes by tumor molecular characteristics.

Cancer Causes Control 2019 Apr 8. Epub 2019 Apr 8.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Background: A preventive potential of high calcium intake against colorectal cancer has been indicated for distal colon cancer, which is inversely associated with high-level CpG island methylator phenotype (CIMP), high-level microsatellite instability (MSI), and BRAF and PIK3CA mutations. In addition, BRAF mutation is strongly inversely correlated with KRAS mutation. We hypothesized that the association between calcium intake and colon cancer risk might vary by these molecular features. Read More

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http://dx.doi.org/10.1007/s10552-019-01165-3DOI Listing
April 2019
1 Read

Effect of Cetuximab and Small Interfering RNA Combination Treatment in NSCLC Cell Lines with Wild Type and Use of as a Possible Biomarker for Treatment Responsiveness.

Yonago Acta Med 2019 Mar 28;62(1):85-93. Epub 2019 Mar 28.

Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.

Background: The epidermal growth factor receptor (EGFR) is a therapeutic target for patients with non-small cell lung cancer (NSCLC). Cetuximab is an anti-EGFR monoclonal antibody that inhibits EGFR signaling and proliferation of colorectal cancer and head and neck cancers. Since only few NSCLC patients benefit from cetuximab therapy, we evaluated a novel combination treatment using cetuximab and small interfering RNA (siRNA) to strongly suppress EGFR signaling and searched for a biomarker in NSCLC cell lines harboring wild-type . Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437414PMC
March 2019
5 Reads

SUVmax and metabolic tumor volume: surrogate image biomarkers of KRAS mutation status in colorectal cancer.

Onco Targets Ther 2019 21;12:2115-2121. Epub 2019 Mar 21.

Department of Neurosurgery, Shandong Province Qianfoshan Hospital of Shandong University, Jinan 250014, Shandong, People's Republic of China,

Purpose: The objective of this study was to explore the association between KRAS mutation status and PET/CT metabolic parameters in colorectal cancer (CRC) patients.

Materials And Methods: One hundred and sixty-four CRC patients were enrolled in this study and received PET/CT examination before operation, then KRAS mutation status was analyzed through pathologically confirmed CRC samples. The association between tumor clinical characteristics and PET/CT metabolic parameters, including maximum standardized uptake value (SUVmax), SUVmean, and metabolic tumor volume (MTV), and KRAS mutation status was analyzed using chi-squared tests, Mann-Whitney tests, and logistic regression analysis. Read More

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http://dx.doi.org/10.2147/OTT.S196725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433102PMC
March 2019
2 Reads

Synthetic miR-143 Inhibits Growth of HER2-Positive Gastric Cancer Cells by Suppressing KRAS Networks Including DDX6 RNA Helicase.

Int J Mol Sci 2019 Apr 5;20(7). Epub 2019 Apr 5.

Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.

Gastric cancer (GC) is one of the most common cancers worldwide. In the clinical setting, the identification of HER2 overexpression in GC was a significant finding, as trastuzumab, an anti-HER2 drug, provides a survival advantage to HER2-positive GC patients. In HER2-postive GC, the dysregulation of PI3K/AKT and MAPK/ERK signaling pathways has been reported, and inhibition of these pathways is an important therapeutic strategy. Read More

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http://dx.doi.org/10.3390/ijms20071697DOI Listing
April 2019
1 Read

Impact of primary cancer features on behaviour of colorectal liver metastases and survival after hepatectomy.

BJS Open 2019 Apr 3;3(2):186-194. Epub 2018 Sep 3.

Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum University of Bologna Bologna Italy.

Background: Markers of tumour biology may be valuable prognostic indicators after hepatic resection of colorectal cancer liver metastases (CRLMs). Identification of the aggressiveness of these metastases might inform the appropriateness of hepatic surgery.

Methods: Patients undergoing liver resection for CRLMs between January 2001 and July 2013 in four tertiary hospitals were reviewed. Read More

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http://dx.doi.org/10.1002/bjs5.100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433312PMC
April 2019
1 Read

Integrative genome-scale DNA Methylation analysis of a large and unselected cohort reveals five distinct subtypes of Colorectal Adenocarcinomas.

Cell Mol Gastroenterol Hepatol 2019 Apr 4. Epub 2019 Apr 4.

Conjoint Gastroenterology Department, QIMR Berghofer Medical Research Institute, Queensland, Australia; School of Medicine, University of Queensland, Queensland, Australia; Pathology Queensland, Queensland, Australia.

Background And Aims: Colorectal cancer is an epigenetically heterogeneous disease, however the extent and spectrum of the CpG Island Methylator Phenotype (CIMP) is not clear.

Methods: Genome scale methylation and transcript expression were measured using the Illumina HM450 DNA methylation and HT12 V3 expression microarrays in 216 unselected colorectal cancers, and findings validated using TCGA 450K and RNA-Seq data. Mutations in epigenetic regulators were assessed using CIMP subtyped Cancer Genome Atlas exomes. Read More

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http://dx.doi.org/10.1016/j.jcmgh.2019.04.002DOI Listing
April 2019
1 Read

HER2 Positivity Predicts Unresponsiveness to EGFR-Targeted Treatment in Metastatic Colorectal Cancer.

Oncologist 2019 Apr 5. Epub 2019 Apr 5.

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy

Background: HER2 amplification is detected in 3% of patients with colorectal cancer (CRC), making tumors in the metastatic setting vulnerable to double pharmacological HER2 blockade. Preclinical findings show that it also might impair response to anti-epidermal growth factor receptor (EGFR) treatment.

Subjects And Methods: Patients with exon 2 wild-type metastatic CRC underwent molecular screening of HER2 positivity by HERACLES criteria (immunohistochemistry 3+ or 2+ in ≥50% of cells, confirmed by fluorescence in situ hybridization). Read More

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http://dx.doi.org/10.1634/theoncologist.2018-0785DOI Listing
April 2019
2 Reads

KRAS and NRAS pyrosequencing screening in Tunisian colorectal cancer patients in 2015.

Heliyon 2019 Mar 19;5(3):e01330. Epub 2019 Mar 19.

Pathology Department, Habib Thameur Hospital, Tunis, Tunisia.

Background: Mutations in KRAS and NRAS often result in constitutive activation of RAS in the epidermal growth factor receptor (EGFR) signaling pathway. Mutations in KRAS exon 2 (codon 12-13) predict resistance to anti-EGFR targeted therapy in patients with metastatic colorectal carcinoma (mCRC). However, it's currently known that a significant proportion of mCRC have RAS mutations outside KRAS exon 2, particularly in exons 3 and 4 of KRAS and exons 2, 3 and 4 of NRAS. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S24058440183737
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http://dx.doi.org/10.1016/j.heliyon.2019.e01330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430077PMC
March 2019
2 Reads

Meta-analysis of the molecular associations of mucinous colorectal cancer.

Br J Surg 2019 May 4;106(6):682-691. Epub 2019 Apr 4.

Department of Surgery, Beaumont Hospital, Dublin, Ireland.

Background: Mucinous differentiation occurs in 5-15 per cent of colorectal adenocarcinomas. This subtype of colorectal cancer responds poorly to chemoradiotherapy and has a worse prognosis. The genetic aetiology underpinning this cancer subtype lacks consensus. Read More

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http://dx.doi.org/10.1002/bjs.11142DOI Listing
May 2019
1 Read

Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients.

Cancer Med 2019 Apr 3. Epub 2019 Apr 3.

Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi, P.R. China.

Objective: This study aims to screen the MSI detection loci suitable for the East Asian colorectal cancer patients. and explore its intratumoral heterogeneity.

Methods: A total of 271 pathological tissues specimens of colorectal cancer were collected. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1002/cam4.2111
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http://dx.doi.org/10.1002/cam4.2111DOI Listing
April 2019
4 Reads

A retrospective analysis on first-line bevacizumab, cetuximab, and panitimumab-containing regimens in patients with RAS-wild metastatic colorectal cancer: A Collaborative Study by Turkish Oncology Group (TOG).

J BUON 2019 Jan-Feb;24(1):136-142

Pamukkale University School of Medicine, Medical Oncology Department, Denizli, Turkey.

Purpose: To compare the efficacy and adverse effect profiles of the first-line treatment of patients with KRAS wild type metastatic colorectal cancer (CRC) in Turkey who were treated based on regimens including bevacizumab, cetuximab and panitumumab.

Methods: This retrospective multicenter observational study involved a total of 238 patients who received chemotherapy in combination with either bevacizumab or cetuximab or panitumumab as first-line therapy for KRAS wild-type metastatic colorectal cancer. Patients with full medical records having pathological diagnosis of CRC adenocarcinoma were included in the study. Read More

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April 2019
4 Reads

5-Arylidene(chromenyl-methylene)-thiazolidinediones: Potential New Agents against Mutant Oncoproteins K-Ras, N-Ras and B-Raf in Colorectal Cancer and Melanoma.

Medicina (Kaunas) 2019 Mar 31;55(4). Epub 2019 Mar 31.

Department of Pharmaceutical chemistry, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 41 Victor Babeș Street, RO-400012 Cluj-Napoca, Romania.

Cancer represents the miscommunication between and within the body cells. The mutations of the oncogenes encoding the MAPK pathways play an important role in the development of tumoral diseases. The mutations of KRAS and BRAF oncogenes are involved in colorectal cancer and melanoma, while the NRAS mutations are associated with melanoma. Read More

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http://dx.doi.org/10.3390/medicina55040085DOI Listing
March 2019
2 Reads

Clinical and Molecular Features of Post-Colonoscopy Colorectal Cancers.

Clin Gastroenterol Hepatol 2019 Mar 29. Epub 2019 Mar 29.

Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah; Department of Medicine (Gastroenterology), (§)Department of Oncological Sciences, University of Utah, Salt Lake City, Utah.

Background & Aims: Post-colonoscopy colorectal cancers (PCCRCs) may arise from missed lesions or due to molecular features of tumors that allow them to grow rapidly. We aimed to compare clinical, pathology, and molecular features of PCCRCs (those detected within 6-60 months of colonoscopy) and detected CRCs (those detected within 6 months of a colonoscopy).

Methods: Within a population-based cross-sectional study of incident CRC cases in Utah (from 1995 through 2009), we identified PCCRCs (those cancers that developed within 5 years of a colonoscopy) and matched the patients by age, sex, and hospital site to patients with detected CRC. Read More

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http://dx.doi.org/10.1016/j.cgh.2019.02.040DOI Listing
March 2019
2 Reads

KRAS Promotes Immunosuppression in Colorectal Cancer.

Authors:

Cancer Discov 2019 Mar 29. Epub 2019 Mar 29.

KRAS drives MDSC-mediated resistance to immune checkpoint blockade in patients with colorectal cancer. Read More

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http://cancerdiscovery.aacrjournals.org/lookup/doi/10.1158/2
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http://dx.doi.org/10.1158/2159-8290.CD-RW2019-043DOI Listing
March 2019
5 Reads

Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures.

PLoS Genet 2019 03 29;15(3):e1008076. Epub 2019 Mar 29.

cpo-Cellular Phenomics & Oncology Berlin-Buch GmbH, Berlin, Germany.

Organoid cultures derived from colorectal cancer (CRC) samples are increasingly used as preclinical models for studying tumor biology and the effects of targeted therapies under conditions capturing in vitro the genetic make-up of heterogeneous and even individual neoplasms. While 3D cultures are initiated from surgical specimens comprising multiple cell populations, the impact of tumor heterogeneity on drug effects in organoid cultures has not been addressed systematically. Here we have used a cohort of well-characterized CRC organoids to study the influence of tumor heterogeneity on the activity of the KRAS/MAPK-signaling pathway and the consequences of treatment by inhibitors targeting EGFR and downstream effectors. Read More

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http://dx.doi.org/10.1371/journal.pgen.1008076DOI Listing
March 2019
2 Reads

Disease Control With FOLFIRI Plus Ziv-aflibercept (zFOLFIRI) Beyond FOLFIRI Plus Bevacizumab: Case Series in Metastatic Colorectal Cancer (mCRC).

Front Oncol 2019 14;9:142. Epub 2019 Mar 14.

Biostatistics and Bioinformatics Facility, Fox Chase Cancer Center, Philadelphia, PA, United States.

The prognosis of patients with metastatic colorectal cancer (mCRC) is poor, especially after failure of initial systemic therapy. The VELOUR study showed modestly prolonged overall survival (OS) with ziv-aflibercept plus 5-fluorouracil, leucovorin, and irinotecan (zFOLFIRI) vs. placebo+FOLFIRI after progression on 5-fluoruracil, leucovorin, and oxaliplatin (FOLFOX) ± bevacizumab. Read More

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http://dx.doi.org/10.3389/fonc.2019.00142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426764PMC
March 2019
2 Reads

Clinical implications of the genetics of sporadic colorectal cancer.

ANZ J Surg 2019 Mar 28. Epub 2019 Mar 28.

Department of Surgery, University of Otago, Christchurch, New Zealand.

Colorectal cancer (CRC) is common and at least 80% of cases are sporadic, without any significant family history. Prognostication and treatment have been relatively empirical for what has become increasingly identified as a genetically heterogeneous disease. There are three main genetic pathways in sporadic CRC: the chromosomal instability pathway, the microsatellite instability pathway and the CpG island methylator phenotype pathway. Read More

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http://dx.doi.org/10.1111/ans.15074DOI Listing
March 2019
1 Read

Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors.

Ann Oncol 2019 Mar 27. Epub 2019 Mar 27.

Drug Development Unit Nashville, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA.

Background: Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a PD-L1 inhibitor, atezolizumab, in patients with solid tumors.

Patients And Methods: This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. Read More

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http://dx.doi.org/10.1093/annonc/mdz113DOI Listing
March 2019
1 Read

Cell-free DNA in the supernatant of pleural effusion can be used to detect driver and resistance mutations, and can guide tyrosine kinase inhibitor treatment decisions.

ERJ Open Res 2019 Feb 25;5(1). Epub 2019 Mar 25.

Dept of Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Objectives: Molecular profiling of tumours has become the mainstay of diagnostics for metastasised solid malignancies and guides personalised treatment, especially in nonsmall cell lung cancer (NSCLC). In current practice, it is often challenging to obtain sufficient tumour material for reliable molecular analysis. Cell-free DNA (cfDNA) in blood or other bio-sources could present an alternative approach to obtain genetic information from the tumour. Read More

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http://dx.doi.org/10.1183/23120541.00016-2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431750PMC
February 2019
1 Read

Impact of primary colorectal Cancer location on the KRAS status and its prognostic value.

BMC Gastroenterol 2019 Mar 27;19(1):46. Epub 2019 Mar 27.

Department of Research, Affiliated Tumor Hospital of Guangxi Medical University, 71 Hedi Road, Nanning, 530021, China.

Background: Colorectal cancer (CRC) originating from the right-sided or left-sided colon is distinct clinicopathological entity. The KRAS status and its prognostic value in CRC remain controversial. This study aimed to investigate the association of KRAS status with clinicopathological features and prognostic value in CRC. Read More

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http://dx.doi.org/10.1186/s12876-019-0965-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437985PMC
March 2019
1 Read

EIF3E-RSPO2 and PIEZO1-RSPO2 fusions in colorectal traditional serrated adenoma.

Histopathology 2019 Mar 27. Epub 2019 Mar 27.

Division of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.

Aims: Traditional serrated adenoma (TSA) is an uncommon type of colorectal serrated polyp. RSPO fusions, which potentiate WNT signaling, are common and characteristic genetic alterations in TSA. The aim of this study was to further characterize the prevalence and variation of RSPO fusions in TSA. Read More

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https://onlinelibrary.wiley.com/doi/abs/10.1111/his.13867
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http://dx.doi.org/10.1111/his.13867DOI Listing
March 2019
3 Reads

Genome-wide Analysis Reveals DNA Methylation Alterations in Obesity Associated with High Risk of Colorectal Cancer.

Sci Rep 2019 Mar 25;9(1):5100. Epub 2019 Mar 25.

Department of Biochemistry & Molecular Biology, Wright State University, 3640 Colonel Glenn Hwy., Dayton, OH, USA.

Obesity is a high risk factor for colorectal cancer (CRC). The contribution of underlying epigenetic mechanisms to CRC and the precise targets of epigenetic alterations during cancer development are largely unknown. Several types of epigenetic processes have been described, including DNA methylation, histone modification, and microRNA expression. Read More

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http://www.nature.com/articles/s41598-019-41616-0
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http://dx.doi.org/10.1038/s41598-019-41616-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433909PMC
March 2019
9 Reads

Dissecting mechanisms of resistance to targeted drug combination therapy in human colorectal cancer.

Oncogene 2019 Mar 25. Epub 2019 Mar 25.

Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, UK.

Genomic alterations in cancer cells result in vulnerabilities that clinicians can exploit using molecularly targeted drugs, guided by knowledge of the tumour genotype. However, the selective activity of these drugs exerts an evolutionary pressure on cancers that can result in the outgrowth of resistant clones. Use of rational drug combinations can overcome resistance to targeted drugs, but resistance may eventually develop to combinatorial therapies. Read More

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http://dx.doi.org/10.1038/s41388-019-0780-zDOI Listing
March 2019
6 Reads

KRAS-IRF2 Axis Drives Immune Suppression and Immune Therapy Resistance in Colorectal Cancer.

Cancer Cell 2019 Apr 21;35(4):559-572.e7. Epub 2019 Mar 21.

Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:

The biological functions and mechanisms of oncogenic KRAS (KRAS) in resistance to immune checkpoint blockade (ICB) therapy are not fully understood. We demonstrate that KRAS represses the expression of interferon regulatory factor 2 (IRF2), which in turn directly represses CXCL3 expression. KRAS-mediated repression of IRF2 results in high expression of CXCL3, which binds to CXCR2 on myeloid-derived suppressor cells and promotes their migration to the tumor microenvironment. Read More

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http://dx.doi.org/10.1016/j.ccell.2019.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467776PMC
April 2019
2 Reads
23.523 Impact Factor

Sensitive and selective detections of codon 12 and 13 KRAS mutations in a single tube using modified wild-type blocker.

Clin Chim Acta 2019 Mar 19;494:123-131. Epub 2019 Mar 19.

Department of Laboratory Medicine, Institute of Surgery Research, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing 400042, China.; Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.; Institute for Clean Energy & Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, China. Electronic address:

It was hypothesized that in the WTB-PCR system, the greater number of cycles, associated with the thermodynamic driving force of DNA polymerase resulted in artificial introduction of mutant nucleotides in amplicons. In the current study, universal WTB-PCR was developed to overcome these limitations, in which two strategies were used: phosphorothioate modifications were made at the 5'-termini bases of the WTB oligonucleotides, and amplification of referenced internal positive controller (RIPC) fragments was performed. The results showed that universal WTB-PCR could detect single-copy KRAS mutant alleles with higher selectivity (i. Read More

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http://dx.doi.org/10.1016/j.cca.2019.03.1618DOI Listing
March 2019
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Association between KRAS G13D mutations and anastomotic recurrence in colorectal cancer: Two case reports.

Medicine (Baltimore) 2019 Mar;98(12):e14781

Rationale: The prevalence of anastomotic recurrence (AR) in colorectal cancer (CRC) after resection of the primary tumor (PT) is 5% to 14%. However, no association has been observed between specific somatic genetic alterations and AR. Such associations may shed light on the mechanism of AR. Read More

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http://dx.doi.org/10.1097/MD.0000000000014781DOI Listing
March 2019
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Necessity of Genetic Evaluation of Metachronous Metastases of Colorectal Cancer: Quantitative Analysis of Genetic Discordance Between Metachronous Metastases and Radically Resected Primary Colorectal Cancers Using Next-Generation Sequencing.

Dis Colon Rectum 2019 Mar 15. Epub 2019 Mar 15.

Department of Surgery, Chungnam National University Hospital, Daejeon, Republic of Korea.

Background: Mutation analyses provide the basis of selecting an appropriate target agent for the treatment of metastatic colorectal cancer. However, metachronous metastases developed after the treatment of primary tumor could create significant opportunities for different genetic profiles relative to the primary tumors.

Objective: The purpose of this study was to assess the necessity of genetic evaluation of metachronous metastases; we performed a quantitative analysis of genetic discordance between metachronous metastases and radically resected primary colorectal cancers using next-generation sequencing. Read More

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http://dx.doi.org/10.1097/DCR.0000000000001386DOI Listing
March 2019
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Utilisation of systemic therapy options in routine treatment of metastatic colorectal cancer in Australia.

Intern Med J 2019 Mar 18. Epub 2019 Mar 18.

Department of Medical Oncology, Eastern Health, Box Hill, Australia.

Background/aim: In the treatment of metastatic colorectal cancer (mCRC), exposure to all three active cytotoxic agents; 5-fluorouracil/capecitabine, irinotecan and oxaliplatin improves overall survival. The addition of biologic agents (bevacizumab and cetuximab/panitumumab) further improves survival. The uptake of available systemic agents for mCRC in routine practice in Australia is poorly described. Read More

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http://dx.doi.org/10.1111/imj.14288DOI Listing
March 2019
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KRAS mutations in the parental tumour accelerate in vitro growth of tumoroids established from colorectal adenocarcinoma.

Int J Exp Pathol 2019 Feb 18;100(1):12-18. Epub 2019 Mar 18.

2cureX, Birkeroed, Denmark.

The aim of the present study was to characterize a patient-derived in vitro 3D model (ie tumoroid) established from colorectal adenocarcinoma. This study investigated the growth rate of tumoroids and whether the Kirsten rat sarcoma (KRAS) mutations in the parental tumour accelerate this rate. The tumoroids were established from surgical resections of primary and metastatic colorectal adenocarcinoma from 26 patients. Read More

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http://dx.doi.org/10.1111/iep.12308DOI Listing
February 2019
2 Reads

Circulating Cell-Free DNA-Diagnostic and Prognostic Applications in Personalized Cancer Therapy.

Ther Drug Monit 2019 04;41(2):115-120

Department of Clinical Pharmacology, University Medical Center Goettingen, Goettingen, Germany.

Genomic analyses in oncologic care allow for the development of more precise clinical laboratory tests that will be critical for personalized pharmacotherapy. Traditional biopsy-based approaches are limited by the availability of sequential tissue specimens to detect resistance. Blood-based genomic profiling ("liquid biopsy") is useful for longitudinal monitoring of tumor genomes and can complement biopsies. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000566DOI Listing
April 2019
5 Reads

A Single-Arm, Phase II Study of Apatinib in Refractory Metastatic Colorectal Cancer.

Oncologist 2019 Mar 15. Epub 2019 Mar 15.

Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China

Lessons Learned: Patients with metastatic colorectal cancer with good performance status or no liver metastasis could benefit from apatinib.Circulating tumor DNA abundance may be a predictor in serial monitoring of tumor load.

Background: Apatinib, an oral vascular endothelial growth factor (VEGF) receptor-2 inhibitor, has been approved as third-line treatment for metastatic gastric cancer in China. Read More

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http://dx.doi.org/10.1634/theoncologist.2019-0164DOI Listing
March 2019
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Detection of KRAS G12D point mutation level by anchor-like DNA electrochemical biosensor.

Authors:
Ni Zeng Juan Xiang

Talanta 2019 Jun 31;198:111-117. Epub 2019 Jan 31.

Hunan Provincial Key Laboratory of Efficient and Clean Utilization of Manganese Resources, Central South University, Changsha 410083, Hunan, PR China; College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, PR China. Electronic address:

KRAS G12D point mutation plays an important role in the incidence of non-small-cell lung cancer (NSCLC) as well as colorectal cancer, pancreatic cancer and breast cancer. Here, we developed a novel anchor-like DNA (alDNA) electrochemical sensor for the detection of KRAS point mutation level (the concentration ratio of the specific KRAS point mutant DNA (M-DNA) to the total DNA (t-DNA) of both mutant and wild-type DNAs carrying the same allele). Compared to those conventional ligation-based DNA sensors, the proposed alDNA sensor achieved the one-step capture of both wild-type and mutant DNA, and the subsequent detection on one chip, which effectively decreased systematic errors from the uncertain differences on the interfacial structural and microenvironmental changes, improved the detection accuracy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00399140193012
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http://dx.doi.org/10.1016/j.talanta.2019.01.105DOI Listing
June 2019
8 Reads

Mutational Analysis of Patients With Colorectal Cancer in CALGB/SWOG 80405 Identifies New Roles of Microsatellite Instability and Tumor Mutational Burden for Patient Outcome.

J Clin Oncol 2019 Mar 13:JCO1801798. Epub 2019 Mar 13.

3 Genentech, South San Francisco, CA.

Purpose: CALGB/SWOG 80405 was a randomized phase III trial that found no statistically significant difference in overall survival (OS) in patients with first-line metastatic colorectal cancer treated with chemotherapy plus either bevacizumab or cetuximab. Primary tumor DNA from 843 patients has been used to discover genetic markers of OS.

Patients And Methods: Gene mutations were determined by polymerase chain reaction. Read More

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http://ascopubs.org/doi/10.1200/JCO.18.01798
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http://dx.doi.org/10.1200/JCO.18.01798DOI Listing
March 2019
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Optimizing sequential treatment with anti-EGFR and VEGF mAb in metastatic colorectal cancer: current results and controversies.

Cancer Manag Res 2019 19;11:1705-1716. Epub 2019 Feb 19.

Wuxi People's Hospital Affiliatedto Nanjing Medical University, Wuxi, People's Republic of China,

Anti-EGFR mAb (cetuximab or panitumumab) and anti-VEGF mAb (bevacizumab) are the two main targeted agents available for RAS wild-type (WT) metastatic colorectal cancer (mCRC) treatment. Nonetheless, three head-to-head clinical trials evaluating anti-EGFR mAb vs -VEGF mAb in first-line treatment failed to conclude a uniform result. Recently, a few small clinical studies revealed that prior use of bevacizumab may impair the effect of cetuximab or panitumumab. Read More

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https://www.dovepress.com/optimizing-sequential-treatment-wi
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http://dx.doi.org/10.2147/CMAR.S196170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388996PMC
February 2019
3 Reads

Meeting report of the 14th Japan-Korea joint symposium on cancer and aging research: current status of translational research and approaches to precision medicine.

J Cancer Res Clin Oncol 2019 Mar 11. Epub 2019 Mar 11.

Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, 00380, South Korea.

Purpose: The 14th Japan-Korea joint symposium on cancer and aging research was held at an auditorium of Saga University, Japan, May 31-Jun 2, 2018. Participants presented 31 oral and 21 poster presentations, two lectures at a luncheon seminar, plus special lectures from two Korean Emeritus Professors and founders of our joint symposia. The essential parts of the lectures are reviewed here. Read More

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http://dx.doi.org/10.1007/s00432-019-02887-2DOI Listing
March 2019
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CRISPR-induced RASGAP deficiencies in colorectal cancer organoids reveal that only loss of NF1 promotes resistance to EGFR inhibition.

Oncotarget 2019 Feb 15;10(14):1440-1457. Epub 2019 Feb 15.

Center for Molecular Medicine, Section Molecular Cancer Research, University Medical Center Utrecht, Utrecht, The Netherlands.

Anti-EGFR therapy is used to treat metastatic colorectal cancer (CRC) patients, for which initial response rates of 10-20% have been achieved. Although the presence of HER2 amplifications and oncogenic mutations in KRAS, NRAS, and BRAF are associated with EGFR-targeted therapy resistance, for a large population of CRC patients the underlying mechanism of RAS-MEK-ERK hyperactivation is not clear. Loss-of-function mutations in RASGAPs are often speculated in literature to promote CRC growth as being negative regulators of RAS, but direct experimental evidence is lacking. Read More

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http://dx.doi.org/10.18632/oncotarget.26677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402720PMC
February 2019

Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in KRAS-mutant Pancreatic and Colorectal Cancer.

Cancer Res 2019 Mar 11. Epub 2019 Mar 11.

Faculty of Chemistry and Chemical Biology, TU Dortmund University

Aberrations within the PI3K/AKT signaling axis are frequently observed in numerous cancer types, highlighting the relevance of these pathways in cancer physiology and pathology. However, therapeutic interventions employing AKT inhibitors often suffer from limitations associated with target selectivity, efficacy, or dose-limiting effects. Here we present the first crystal structure of auto-inhibited AKT1 in complex with the covalent-allosteric inhibitor borussertib, providing critical insights into the structural basis of AKT1 inhibition by this unique class of compounds. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2861DOI Listing
March 2019
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Clinicopathological and molecular differences in colorectal cancer according to location.

Int J Biol Markers 2019 Mar 10:1724600818807164. Epub 2019 Mar 10.

1 Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.

Purpose:: The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC).

Materials And Methods:: A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Read More

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http://dx.doi.org/10.1177/1724600818807164DOI Listing
March 2019
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G12V Mutation is an Adverse Prognostic Factor of Chinese Gastric Cancer Patients.

J Cancer 2019 29;10(4):821-828. Epub 2019 Jan 29.

Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong, China.

This study aims to investigate the molecular characteristics of Chinese gastric cancer patients. In our study, the , , and mutation status of 485 GC patients were analyzed by Sanger sequencing. Kaplan-Meier analysis was used to plot survival curves according to different genotypes. Read More

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http://www.jcancer.org/v10p0821.htm
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http://dx.doi.org/10.7150/jca.27899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400811PMC
January 2019
5 Reads