Circulating tumor cells: exploring intratumor heterogeneity of colorectal cancer.

Abstract:

:The hypothesis of the "liquid biopsy" using circulating tumor cells (CTCs) emerged as a minimally invasive alternative to traditional tissue biopsy to determine cancer therapy. Discordance for biomarkers expression between primary tumor tissue and circulating tumor cells (CTCs) has been widely reported, thus rendering the biological characterization of CTCs an attractive tool for biomarkers assessment and treatment selection. Studies performed in metastatic colorectal cancer (mCRC) patients using CellSearch, the only FDA-cleared test for CTCs assessment, demonstrated a much lower yield of CTCs in this tumor type compared with breast and prostate cancer, both at baseline and during the course of treatment. Thus, although attractive, the possibility to use CTCs as therapy-related biomarker for colorectal cancer patients is still limited by a number of technical issues mainly due to the low sensitivity of the CellSearch method. In the present study we found a significant discordance between CellSearch and AdnaTest in the detection of CTCs from mCRC patients. We then investigated KRAS pathway activating mutations in CTCs and determined the degree of heterogeneity for KRAS oncogenic mutations between CTCs and tumor tissues. Whether KRAS gene amplification may represent an alternative pathway responsible for KRAS activation was further explored. KRAS gene amplification emerged as a functionally equivalent and mutually exclusive mechanism of KRAS pathway activation in CTCs, possibly related to transcriptional activation. The serial assessment of CTCs may represent an early biomarker of treatment response, able to overcome the intrinsic limit of current molecular biomarkers represented by intratumor heterogeneity.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Raimondi C,Nicolazzo C,Gradilone A,Giannini G,De Falco E,Chimenti I,Varriale E,Hauch S,Plappert L,Cortesi E,Gazzaniga P

doi

10.4161/cbt.28020

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

496-503

issue

5

eissn

1538-4047

issn

1555-8576

pii

28020

journal_volume

15

pub_type

杂志文章
  • The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity.

    abstract::Because of its high mortality rate, ovarian cancer is a leading cause of death among women and a highly unmet medical need. New therapeutic agents that are effective and well tolerated are needed and cancer antigen-specific monoclonal antibodies that have direct pharmacologic effects or can stimulate immunological res...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.26106

    authors: Lin J,Spidel JL,Maddage CJ,Rybinski KA,Kennedy RP,Krauthauser CL,Park YC,Albone EF,Jacob S,Goserud MT,Martinez BP,Chao Q,Zhou Y,Nicolaides NC,Kline JB,Grasso L

    更新日期:2013-11-01 00:00:00

  • Gemcitabine resistant pancreatic cancer cell lines acquire an invasive phenotype with collateral hypersensitivity to histone deacetylase inhibitors.

    abstract::Gemcitabine based treatment is currently a standard first line treatment for patients with advanced pancreatic cancer, however overall survival remains poor, and few options are available for patients that fail gemcitabine based therapy. To identify potential molecular targets in gemcitabine refractory pancreatic canc...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/15384047.2014.986967

    authors: Samulitis BK,Pond KW,Pond E,Cress AE,Patel H,Wisner L,Patel C,Dorr RT,Landowski TH

    更新日期:2015-01-01 00:00:00

  • PIK3R3 promotes chemotherapeutic sensitivity of colorectal cancer through PIK3R3/NF-kB/TP pathway.

    abstract::Phosphoinositide-3-kinase regulatory subunit 3(PIK3R3) is overexpressed in different types of human cancer. We previously reported the important role of PIK3R3 in colorectal cancer (CRC). However, the prognosis effect of PIK3R3 in CRC is still remaining unclear. In this study, we explored online clinical databases to ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1416936

    authors: Ibrahim S,Li G,Hu F,Hou Z,Chen Q,Li G,Luo X,Hu J,Feng Y

    更新日期:2018-03-04 00:00:00

  • TMPRSS4 correlates with colorectal cancer pathological stage and regulates cell proliferation and self-renewal ability.

    abstract::Transmembrane protease/serine 4 (TMPRSS4) is a member of the type II transmembrane serine protease (TTSP) family and it was found highly expressed in several cancers. This study aims to evaluate the expression of TMPRSS4 in colorectal cancer (CRC) and investigate its role in proliferation and self-renewal of colon can...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.27308

    authors: Huang A,Zhou H,Zhao H,Quan Y,Feng B,Zheng M

    更新日期:2014-03-01 00:00:00

  • Comparitive study of efficacy, tolerability of four field box technique vs. two field anterior posterior technique in locally advanced carcinoma cervix--a prospective analysis.

    abstract:PURPOSE:The pelvic failure rate decreases with increase in the radiation dose but the complications increase. The four field pelvic technique has a theoretical advantage of providing a higher tumor dose with less dose to the surrounding normal tissue thus reducing the complications. RESULT:Eighty-three patients comple...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,随机对照试验

    doi:10.4161/cbt.8.9.8129

    authors: Gupta D,Shukla P,Bisht SS,Aggarwal A,Dhawan A,Pant MC,Bhatt ML,Gupta R,Srivastava K,Gupta S,Srivastava M

    更新日期:2009-05-01 00:00:00

  • Gefitinib-sensitizing mutation in esophageal carcinoma cell line Kyse450.

    abstract:PURPOSE:The sensitivity of lung cancer to gefitinib has been found to be associated with mutations at the tyrosine kinase domain of epidermal growth factor receptor (EGFR), yet similar observations are not available in other solid tumors. We recently identified mutations in the EGFR kinase domain in primary esophageal ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.5.2.2318

    authors: Guo M,Liu S,Herman JG,Zhuang H,Lu F

    更新日期:2006-02-01 00:00:00

  • Acquired resistance of lung adenocarcinoma to EGFR-tyrosine kinase inhibitors gefitinib and erlotinib.

    abstract::Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are the first targeted therapy drugs approved for the treatment of advanced non-small-cell lung cancer (NSCLC). Interestingly, treatment with these small molecule, reversible EGFR-TKIs leads to more positive respo...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.4161/cbt.9.8.11881

    authors: Xu Y,Liu H,Chen J,Zhou Q

    更新日期:2010-04-15 00:00:00

  • Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells.

    abstract::Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in 3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the ro...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2016.1235658

    authors: Rahal ON,Fatfat M,Hankache C,Osman B,Khalife H,Machaca K,Muhtasib HG

    更新日期:2016-11-01 00:00:00

  • FGFR genes mutation is an independent prognostic factor and associated with lymph node metastasis in squamous non-small cell lung cancer.

    abstract::Targeting FGFRs is one of the most promising therapeutic strategies in squamous non-small cell lung cancer (SQCC). However, different FGFR genomic aberrations can be associated with distinct biological characteristics that result in different clinical outcomes or therapeutic consequences. Currently, the full spectrum ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2018.1480294

    authors: Li JJ,Yan S,Pan Y,Liu Z,Liu Y,Deng Q,Tan Q,Woodward ER,Wu N

    更新日期:2018-01-01 00:00:00

  • Aggressive myeloid leukemia formation is directed by the Musashi 2/Numb pathway.

    abstract::Chronic myeloid leukemia (CML) progresses from a chronic phase to a deadly blast crisis phase. While it is known that BCR-ABL initiates the disease and that secondary molecular and genetic abnormalities likely contribute to progression of the disease to blast crisis, details regarding the mechanism(s) of blast phase p...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.10.14010

    authors: Griner LN,Reuther GW

    更新日期:2010-11-15 00:00:00

  • Negative regulation of the oncogenic transcription factor FoxM1 by thiazolidinediones and mithramycin.

    abstract::The Forkhead Box transcription factor FoxM1 regulates expression of genes that promote cell cycle progression, and it plays essential roles in the development of liver, lung, prostate and colorectal tumors. Thiazolidinediones (TZDs) activate the peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activa...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.9.12.11710

    authors: Petrovic V,Costa RH,Lau LF,Raychaudhuri P,Tyner AL

    更新日期:2010-06-15 00:00:00

  • Polymorphisms of p53 and MDM2 genes are associated with severe toxicities in patients with non-small cell lung cancer.

    abstract::Adverse events in platinum-based chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) are major challenges. In this study, we investigated the role of the p53 and MDM2 genes in predicting adverse events in NSCLC patients treated with platinum-based chemotherapy. Specifically, we examined the p53 ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/15384047.2014.956599

    authors: Zheng D,Chen Y,Gao C,Wei Y,Cao G,Lu N,Hou Y,Jiang X,Wang J

    更新日期:2014-01-01 00:00:00

  • Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses.

    abstract::As a kinase at the crossroads of numerous metabolic and cell growth signaling pathways, glycogen synthase kinase-3 beta (GSK-3β) is a highly desirable therapeutic target in cancer. Despite its involvement in pathways associated with the pathogenesis of several malignancies, no selective GSK-3β inhibitor has been appro...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.1080/15384047.2019.1595283

    authors: Sahin I,Eturi A,De Souza A,Pamarthy S,Tavora F,Giles FJ,Carneiro BA

    更新日期:2019-01-01 00:00:00

  • Divergent control of Cav-1 expression in non-cancerous Li-Fraumeni syndrome and human cancer cell lines.

    abstract::Li-Fraumeni syndrome (LFS) is primarily characterized by development of tumors exhibiting germ-line mutations in the p53 gene. Cell lines developed from patients of a LFS family have decreased p53 activity as evidenced by the absence of apoptosis upon etoposide treatment. To test our hypothesis that changes in gene ex...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.22621

    authors: Sherif ZA,Sultan AS

    更新日期:2013-01-01 00:00:00

  • In Vitro and In Vivo evaluation of a novel folate-targeted theranostic nanoemulsion of docetaxel for imaging and improved anticancer activity against ovarian cancers.

    abstract::Ovarian cancer ranks fifth in cancer related deaths for women in USA. The high mortality rate associated with ovarian cancer is due to diagnosis at later stages of disease and the high recurrence rate of 60-80%. Recurrent ovarian cancers are more likely to present as multidrug resistance (MDR) leading to unfavorable r...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2017.1395118

    authors: Patel NR,Piroyan A,Ganta S,Morse AB,Candiloro KM,Solon AL,Nack AH,Galati CA,Bora C,Maglaty MA,O'Brien SW,Litwin S,Davis B,Connolly DC,Coleman TP

    更新日期:2018-07-03 00:00:00

  • 17beta-estradiol and tamoxifen stimulate rapid and transient ERK activationin MCF-7 cells via distinct signaling mechanisms.

    abstract::Traditionally, estrogen signaling was thought to be mediated strictly through genomic pathways. Recently, however, it has been demonstrated that estrogen stimulation of cells leads to rapid nongenomic effects including ERK activation. While the precise mechanism of this action is still under investigation, it is known...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.5.12.3378

    authors: Visram H,Greer PA

    更新日期:2006-12-01 00:00:00

  • Successful treatment using apatinib with or without docetaxel in heavily pretreated advanced non-squamous non-small cell lung cancer: A case report and literature review.

    abstract::Although targeted therapy directed toward driver mutations has produced a significant efficacy benefit for patients with non-small cell lung cancer (NSCLC), many patients do not possess mutations associated with the approved targeted drugs. Angiogenic agents play an important role in the therapeutic strategy for advan...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章,评审

    doi:10.1080/15384047.2017.1414757

    authors: Wu F,Zhang S,Gao G,Zhao J,Ren S,Zhou C

    更新日期:2018-03-04 00:00:00

  • Novel surface targets and serum biomarkers from the ovarian cancer vasculature.

    abstract::The molecular phenotype of tumor vasculature is different from normal vasculature, offering new opportunities for diagnosis and therapy of cancer, but the identification of tumor-restricted targets remains a challenge. We investigated 13 tumor vascular markers (TVMs) from 50 candidates identified through expression pr...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.12.3.16260

    authors: Sasaroli D,Gimotty PA,Pathak HB,Hammond R,Kougioumtzidou E,Katsaros D,Buckanovich R,Devarajan K,Sandaltzopoulos R,Godwin AK,Scholler N,Coukos G

    更新日期:2011-08-01 00:00:00

  • Bruton's tyrosine kinase is a potential therapeutic target in prostate cancer.

    abstract::Bruton's tyrosine kinase (BTK) is a non-receptor tyrosine kinase that has mainly been studied in haematopoietic cells. We have investigated whether BTK is a potential therapeutic target in prostate cancer. We find that BTK is expressed in prostate cells, with the alternate BTK-C isoform predominantly expressed in pros...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1078023

    authors: Kokabee L,Wang X,Sevinsky CJ,Wang WL,Cheu L,Chittur SV,Karimipoor M,Tenniswood M,Conklin DS

    更新日期:2015-01-01 00:00:00

  • Anti-EGFR therapeutic efficacy correlates directly with inhibition of STAT3 activity.

    abstract::Several agents targeting the epidermal growth factor receptor (EGFR) have been FDA-approved to treat cancer patients with varying tumor types including metastatic colorectal cancer. Many patients treated with anti-EGFR therapy however do not respond and those that do initially respond often acquire resistance. Here we...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.28179

    authors: Ung N,Putoczki TL,Stylli SS,Ng I,Mariadason JM,Chan TA,Zhu HJ,Luwor RB

    更新日期:2014-05-01 00:00:00

  • Comparison of genetic changes between interphase and metaphase nuclei in monitoring CML and APL treatment using DC-FISH technique.

    abstract::In leukemias, the monitoring techniques on the response after the treatment have clinical importance for evaluating new therapeutic approaches and identifying the risk of relapse. In this study, genetic changes before and after chemotherapy in interphase and metaphase nuclei of bone morrow of adults with provisional d...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.9.1039

    authors: Yakut T,Ali R,Egeli U,Ozkalemkas F,Ercan I,Ozçelik T,Ozkocaman V,Yigit B,Tunali A

    更新日期:2004-09-01 00:00:00

  • Characterization of a specific phage-displayed Peptide binding to vasculature of human gastric cancer.

    abstract::Antivascular therapy provides a promising method for anticancer therapy. But targeting to gastric cancer vessels is nonselective due in part to the lack of specific cell-surface receptors identified on target vascular cells. Herein we used in vivo screening of phage displayed peptide library to identify some peptides ...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.12.1223

    authors: Zhi M,Wu KC,Dong L,Hao ZM,Deng TZ,Hong L,Liang SH,Zhao PT,Qiao TD,Wang Y,Xu X,Fan DM

    更新日期:2004-12-01 00:00:00

  • Expression analysis of liver-specific circulating microRNAs in HCV-induced hepatocellular Carcinoma in Egyptian patients.

    abstract:OBJECTIVES:Due to the absence of reliable and accurate biomarkers for the early detection of liver malignancy, circulating microRNAs have recently emerged as great candidates for prompt cancer identification. Therefore, the aim of this study was to investigate the potential of liver-specific circulating microRNAs as an...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2018.1423922

    authors: Mourad L,El-Ahwany E,Zoheiry M,Abu-Taleb H,Hassan M,Ouf A,Rahim AA,Hassanien M,Zada S

    更新日期:2018-05-04 00:00:00

  • Lack of p38 MAP kinase activation in TRAIL-resistant cells is not related to the resistance to TRAIL-mediated cell death.

    abstract::Activation of MAP kinases is involved in various cellular processes, including immunoregulation, inflammation, cell growth, cell differentiation, and cell death. To investigate the role of p38 MAP kinase activation in the signaling pathway of TRAIL-mediated apoptosis, we compared TRAIL-mediated MAP kinase activation i...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.3.3.696

    authors: Zhang L,Zhu H,Davis JJ,Jacob D,Wu S,Teraishi F,Gutierrez A,Wang Y,Fang B

    更新日期:2004-03-01 00:00:00

  • DNA ploidy and S phase fraction of breast and ovarian tumor cells treated with a natural anthracycline analog (aloin).

    abstract::DNA ploidy and S phase fraction analysis by flow cytometry on breast and ovarian tumor cells continuously exposed to aloin, a natural anthraquinone, at two concentrations (20-60 microg/ml) was done. Untreated breast and ovarian tumor cells (control) showed an aneuploid pattern, with a mean DNA index of 2.10+/-0.10 and...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.4.1.1445

    authors: Esmat AY,El-Gerzawy SM,Rafaat A

    更新日期:2005-01-01 00:00:00

  • Discussing the predictive, prognostic, and therapeutic value of germline DNA-repair gene mutations in metastatic prostate cancer patients.

    abstract::Recent trends in cancer therapy have begun emphasizing the use of precision medicine, especially genetic tools, in the evaluation of malignancies and decision-making. Prostate cancer is a malignancy where the benefits and utility of screening and early treatment are still heavily controversial. A recent paper in the N...

    journal_title:Cancer biology & therapy

    pub_type: 评论,杂志文章

    doi:10.1080/15384047.2017.1345398

    authors: Hauke RJ Jr,Sissung TM,Figg WD

    更新日期:2017-08-03 00:00:00

  • Low density lipoprotein receptor mediates anti-VEGF effect of lymphocyte T-derived microparticles in Lewis lung carcinoma cells.

    abstract::Nonstop proliferation and vigorous neovascularization are two prominent characteristics of cancer. Antiangiogenic therapy has emerged as an important modality in treatment of solid tumors. Our previous work demonstrated that microparticles derived from apoptotic T-lymphocytes (LMPs) not only reduced the viabilities of...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.10.5.12533

    authors: Yang C,Gagnon C,Hou X,Hardy P

    更新日期:2010-09-01 00:00:00

  • Emodin enhances cytotoxicity of chemotherapeutic drugs in prostate cancer cells: the mechanisms involve ROS-mediated suppression of multidrug resistance and hypoxia inducible factor-1.

    abstract::The intrinsic or acquired resistance to multiple drugs (MDR) of cancer cells remains one of the main obstacles for chemotherapy. Development of small molecule targeting to hypoxia inducible factor-1 (HIF-1) has been recently proposed as strategy for treatments of drug-resistant solid tumors. In the present study, emod...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.3.5457

    authors: Huang XZ,Wang J,Huang C,Chen YY,Shi GY,Hu QS,Yi J

    更新日期:2008-03-01 00:00:00

  • A homologous promoterless K-ras cDNA targeting endogenous K-ras expression inhibits human pancreatic cancer cell growth in vitro and in vivo.

    abstract::It has been reported that the local introduction of a promoter-less DNA containing the complementary DNA (cDNA) sequence of a gene could induce gene-specific silencing in plants. The feasibility of this kind of silencing in human cancer cells is as yet unknown. The current study was designed to investigate the anti-tu...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.4161/cbt.7.10.6586

    authors: Ren XY,Liang ZY,Shi XH,Liu TH

    更新日期:2008-10-01 00:00:00

  • CXCL4 mediates tumor regrowth after chemotherapy by suppression of antitumor immunity.

    abstract::The recurrence of colorectal cancer after chemotherapy is the leading cause of its high mortality. We propose that elucidating the mechanisms of tumor regrowth after chemotherapy in tumor-bearing mice may provide new insights into tumor relapse in cancer patients. We firstly report the identification of a chemokine, C...

    journal_title:Cancer biology & therapy

    pub_type: 杂志文章

    doi:10.1080/15384047.2015.1095404

    authors: Zhang Y,Gao J,Wang X,Deng S,Ye H,Guan W,Wu M,Zhu S,Yu Y,Han W

    更新日期:2015-01-01 00:00:00