Review
. 2010 Jun;7(7).
doi: 10.1038/nrclinonc.2010.84.

Molecular circuits of solid tumors: prognostic and predictive tools for bedside use

Charles Ferté 1 Fabrice André  Jean-Charles Soria  
Affiliations
  • PMID: 20551944
  •     121 References
  •     46 citations

Abstract

The explosion of knowledge in cancer biology in the past two decades has led to the identification of specific molecular circuits in solid tumors. These pathways reflect specific abnormalities thought to drive malignant progression. This knowledge has also generated a vast panel of cancer biomarkers although many of these biomarkers lack sufficient research and validation to be used in the clinic. This Review discusses relevant molecular prognostic and/or predictive biomarkers in the six leading tumors with the highest contribution to cancer mortality: breast, lung, colorectal, prostate, pancreatic and ovarian cancer. Each biomarker is described according to its associated clinicopathological presentation and specific associated molecular interactions. Despite only few biomarkers being currently implemented in clinical practice, a new generation of predictors is emerging that could modify the classic organ-based cancer classification (for example, defects in DNA repair, aberrant MAPK signaling and aberrant PI3K/Akt/mTOR signaling). The advent of high-throughput strategies will also probably substitute monobiomarker strategies.

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Robert C Bast, Bryan Hennessy, Gordon B Mills.
Nat Rev Cancer, 2009 May 23; 9(6). PMID: 19461667    Free PMC article.
Highly Cited. Review.
Proliferative markers as prognostic and predictive tools in early breast cancer: where are we now?
M Colozza, E Azambuja, +3 authors, M J Piccart.
Ann Oncol, 2005 Jun 28; 16(11). PMID: 15980158
Review.
Value and limitations of measuring HER-2 extracellular domain in the serum of breast cancer patients.
Alexandra F Leary, Wedad M Hanna, +5 authors, Mitch Dowsett.
J Clin Oncol, 2009 Mar 04; 27(10). PMID: 19255333
Review.
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
Manabu Soda, Young Lim Choi, +15 authors, Hiroyuki Mano.
Nature, 2007 Jul 13; 448(7153). PMID: 17625570
Highly Cited.
BRAF mutation in metastatic colorectal cancer.
Jolien Tol, Iris D Nagtegaal, Cornelis J A Punt.
N Engl J Med, 2009 Jul 03; 361(1). PMID: 19571295
Highly Cited.
Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma.
Gad Singer, Robert Oldt, +4 authors, Ie-Ming Shih.
J Natl Cancer Inst, 2003 Mar 20; 95(6). PMID: 12644542
Highly Cited.
A five-gene signature and clinical outcome in non-small-cell lung cancer.
Hsuan-Yu Chen, Sung-Liang Yu, +14 authors, Pan-Chyr Yang.
N Engl J Med, 2007 Jan 05; 356(1). PMID: 17202451
Highly Cited.
Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis.
Matthew R Cooperberg, Jeanette M Broering, Peter R Carroll.
J Natl Cancer Inst, 2009 Jun 11; 101(12). PMID: 19509351    Free PMC article.
Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1.
F Jänicke, A Prechtl, +8 authors, German N0 Study Group.
J Natl Cancer Inst, 2001 Jun 21; 93(12). PMID: 11416112
Prevalence of TMPRSS2-ERG fusion prostate cancer among men undergoing prostate biopsy in the United States.
Juan-Miguel Mosquera, Rohit Mehra, +13 authors, Martin G Sanda.
Clin Cancer Res, 2009 Jul 09; 15(14). PMID: 19584163    Free PMC article.
Translational Medicine is developing in China: a new venue for collaboration.
Xiangdong Wang, Ena Wang, Francesco M Marincola.
J Transl Med, 2011 Jan 06; 9. PMID: 21205297    Free PMC article.
Methodological and practical challenges for personalized cancer therapies.
Ignacio I Wistuba, Juri G Gelovani, +2 authors, Roy S Herbst.
Nat Rev Clin Oncol, 2011 Mar 03; 8(3). PMID: 21364686
Review.
Tissue biomarkers as predictors of outcome and selection of transplant candidates with hepatocellular carcinoma.
Josep M Llovet, Valerie Paradis, Masatoshi Kudo, Jessica Zucman-Rossi.
Liver Transpl, 2011 May 20; 17 Suppl 2. PMID: 21594967    Free PMC article.
Review.
Uptake of KRAS mutation testing in patients with metastatic colorectal cancer in Europe, Latin America and Asia.
Fortunato Ciardiello, Sabine Tejpar, +4 authors, Eric Van Cutsem.
Target Oncol, 2011 Jun 02; 6(3). PMID: 21630045
Novel PI3K/Akt inhibitors screened by the cytoprotective function of human immunodeficiency virus type 1 Tat.
Yuri Kim, Joseph A Hollenbaugh, Dong-Hyun Kim, Baek Kim.
PLoS One, 2011 Jul 19; 6(7). PMID: 21765914    Free PMC article.
Prognostic biomarkers in ovarian cancer.
Jie Huang, Wei Hu, Anil K Sood.
Cancer Biomark, 2010 Jan 01; 8(4-5). PMID: 22045356    Free PMC article.
Review.
IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin up-regulation.
Hernan Roca, Matthew J Craig, +8 authors, Kenneth J Pienta.
J Cell Biochem, 2011 Dec 17; 113(5). PMID: 22174091    Free PMC article.
Dramatic reduction of sequence artefacts from DNA isolated from formalin-fixed cancer biopsies by treatment with uracil- DNA glycosylase.
Hongdo Do, Alexander Dobrovic.
Oncotarget, 2012 May 31; 3(5). PMID: 22643842    Free PMC article.
MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer.
S T Guo, C C Jiang, +10 authors, X D Zhang.
Oncogene, 2012 Jun 20; 32(15). PMID: 22710713    Free PMC article.
Highly Cited.
Hemopexin as biomarkers for analyzing the biological responses associated with exposure to silica nanoparticles.
Kazuma Higashisaka, Yasuo Yoshioka, +12 authors, Yasuo Tsutsumi.
Nanoscale Res Lett, 2012 Oct 09; 7(1). PMID: 23039107    Free PMC article.
ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer.
Alec Vaezi, Chelsea H Feldman, Laura J Niedernhofer.
Pharmgenomics Pers Med, 2011 Jan 01; 4. PMID: 23226053    Free PMC article.
PI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma.
Yan Ye, Lei Jin, +18 authors, Xu Dong Zhang.
Nat Commun, 2013 Feb 28; 4. PMID: 23443536    Free PMC article.
Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease--a combined tissue microarray, in vitro and in vivo study.
Ágnes Márk, Melinda Hajdu, +8 authors, Anna Sebestyén.
BMC Cancer, 2013 May 23; 13. PMID: 23693095    Free PMC article.
Impact of bioinformatic procedures in the development and translation of high-throughput molecular classifiers in oncology.
Charles Ferté, Andrew D Trister, +8 authors, Stephen H Friend.
Clin Cancer Res, 2013 Jun 20; 19(16). PMID: 23780890    Free PMC article.
Review.
Loss of PI(4,5)P2 5-Phosphatase A Contributes to Resistance of Human Melanoma Cells to RAF/MEK Inhibitors.
Yan Ye, Qun Li, +5 authors, Sen Yang.
Transl Oncol, 2013 Aug 03; 6(4). PMID: 23908690    Free PMC article.
The role of personalized medicine in metastatic colorectal cancer: an evolving landscape.
Sing Yu Moorcraft, Elizabeth C Smyth, David Cunningham.
Therap Adv Gastroenterol, 2013 Sep 05; 6(5). PMID: 24003339    Free PMC article.
LY294002 and Rapamycin promote coxsackievirus-induced cytopathic effect and apoptosis via inhibition of PI3K/AKT/mTOR signaling pathway.
Zhiheng Chen, Li Yang, +4 authors, Zuocheng Yang.
Mol Cell Biochem, 2013 Sep 28; 385(1-2). PMID: 24072614
Clinical development of phosphatidylinositol 3-kinase inhibitors for non-Hodgkin lymphoma.
Xiaosheng Fang, Xiangxiang Zhou, Xin Wang.
Biomark Res, 2013 Nov 21; 1(1). PMID: 24252186    Free PMC article.
Possible role of autophagy in the treatment of pancreatic cancer with histone deacetylase inhibitors.
Hidemi Rikiishi.
Cancers (Basel), 2010 Jan 01; 2(4). PMID: 24281216    Free PMC article.
Systematic assessment of analytical methods for drug sensitivity prediction from cancer cell line data.
In Sock Jang, Elias Chaibub Neto, +2 authors, Adam A Margolin.
Pac Symp Biocomput, 2013 Dec 04;. PMID: 24297534    Free PMC article.
Targeted-capture massively-parallel sequencing enables robust detection of clinically informative mutations from formalin-fixed tumours.
Stephen Q Wong, Jason Li, +5 authors, Alexander Dobrovic.
Sci Rep, 2013 Dec 18; 3. PMID: 24336498    Free PMC article.
CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis.
Qiang Ding, Yumi Miyazaki, +3 authors, Sonshin Takao.
Mol Cancer, 2014 Jan 29; 13. PMID: 24468059    Free PMC article.
Performance of amplicon-based next generation DNA sequencing for diagnostic gene mutation profiling in oncopathology.
Daoud Sie, Peter J F Snijders, +11 authors, Daniëlle A M Heideman.
Cell Oncol (Dordr), 2014 Sep 12; 37(5). PMID: 25209392
The importance of autophagy regulation in breast cancer development and treatment.
Joanna Magdalena Zarzynska.
Biomed Res Int, 2014 Oct 16; 2014. PMID: 25317422    Free PMC article.
Review.
Prediction of individual response to anticancer therapy: historical and future perspectives.
Florian T Unger, Irene Witte, Kerstin A David.
Cell Mol Life Sci, 2014 Nov 13; 72(4). PMID: 25387856    Free PMC article.
Review.
TrkC expression predicts favorable clinical outcome in invasive ductal carcinoma of breast independent of NT-3 expression.
Wei Zhang, Zhi-Chun Lin, +4 authors, Yun Niu.
Am J Cancer Res, 2014 Dec 19; 4(6). PMID: 25520870    Free PMC article.
Stepwise group sparse regression (SGSR): gene-set-based pharmacogenomic predictive models with stepwise selection of functional priors.
In Sock Jang, Rodrigo Dienstmann, Adam A Margolin, Justin Guinney.
Pac Symp Biocomput, 2015 Jan 17;. PMID: 25592566    Free PMC article.
Point-of-care testing in the diagnosis of gastrointestinal cancers: current technology and future directions.
Jeremy R Huddy, Melody Z Ni, Sheraz R Markar, George B Hanna.
World J Gastroenterol, 2015 Apr 22; 21(14). PMID: 25892860    Free PMC article.
Review.
Automated Analysis and Classification of Histological Tissue Features by Multi-Dimensional Microscopic Molecular Profiling.
Daniel P Riordan, Sushama Varma, Robert B West, Patrick O Brown.
PLoS One, 2015 Jul 16; 10(7). PMID: 26176839    Free PMC article.
INPP4B is an oncogenic regulator in human colon cancer.
S T Guo, M N Chi, +21 authors, C C Jiang.
Oncogene, 2015 Sep 29; 35(23). PMID: 26411369    Free PMC article.
Locus-specific gene repositioning in prostate cancer.
Marc Leshner, Michelle Devine, +3 authors, Karen J Meaburn.
Mol Biol Cell, 2015 Nov 14; 27(2). PMID: 26564800    Free PMC article.
INPP4B is upregulated and functions as an oncogenic driver through SGK3 in a subset of melanomas.
Meng Na Chi, Su Tang Guo, +12 authors, Xu Dong Zhang.
Oncotarget, 2015 Nov 18; 6(37). PMID: 26573229    Free PMC article.
UHRF1 overexpression is involved in cell proliferation and biochemical recurrence in prostate cancer after radical prostatectomy.
Xuechao Wan, Shu Yang, +6 authors, Yao Li.
J Exp Clin Cancer Res, 2016 Feb 18; 35. PMID: 26884069    Free PMC article.
Spatial Genome Organization and Its Emerging Role as a Potential Diagnosis Tool.
Karen J Meaburn.
Front Genet, 2016 Aug 11; 7. PMID: 27507988    Free PMC article.
Review.
Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways.
Weiwei Tan, Meihong Pan, +3 authors, Hongda Liu.
Onco Targets Ther, 2017 Aug 02; 10. PMID: 28761355    Free PMC article.
Short-term spheroid culture of primary colorectal cancer cells as an in vitro model for personalizing cancer medicine.
Maria Jeppesen, Grith Hagel, +6 authors, Jacob Thastrup.
PLoS One, 2017 Sep 07; 12(9). PMID: 28877221    Free PMC article.
Targetable Clinical Nanoparticles for Precision Cancer Therapy Based on Disease-Specific Molecular Inflection Points.
Charalambos Kaittanis, Alexander Bolaender, +3 authors, Jan Grimm.
Nano Lett, 2017 Oct 17; 17(11). PMID: 29035540    Free PMC article.
A three gene immunohistochemical panel serves as an adjunct to clinical staging of patients with head and neck cancer.
Chin-Ann J Ong, Nicholas B Shannon, +15 authors, N Gopalakrishna Iyer.
Oncotarget, 2017 Nov 08; 8(45). PMID: 29108335    Free PMC article.
Prostate-specific membrane antigen cleavage of vitamin B9 stimulates oncogenic signaling through metabotropic glutamate receptors.
Charalambos Kaittanis, Chrysafis Andreou, +14 authors, Jan Grimm.
J Exp Med, 2017 Nov 17; 215(1). PMID: 29141866    Free PMC article.
Blank spots on the map: some current questions on nuclear organization and genome architecture.
Carmen Adriaens, Leonid A Serebryannyy, +10 authors, Tom Misteli.
Histochem Cell Biol, 2018 Sep 22; 150(6). PMID: 30238154    Free PMC article.
Review.
Decreased cytoplasmic expression of Raptor correlates with disease progression and unfavorable prognosis in hepatocellular carcinoma.
Shisi Huang, Xian Lin, +3 authors, Rongcheng Luo.
Int J Clin Exp Pathol, 2017 Dec 01; 10(12). PMID: 31966542    Free PMC article.
Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo.
Lu Zhang, Di Jing, +10 authors, Kit S Lam.
Nat Nanotechnol, 2020 Jan 29; 15(2). PMID: 31988501    Free PMC article.
Investigating Programmed Cell Death and Tumor Invasion in a Three-Dimensional (3D) Microfluidic Model of Glioblastoma.
Ehsan Samiei, Amir Seyfoori, +2 authors, Mohsen Akbari.
Int J Mol Sci, 2020 May 06; 21(9). PMID: 32365781    Free PMC article.
Lung and Abdominal Biopsies in the Age of Precision Medicine.
Leonard Dalag, Jonathan K Fergus, Steven M Zangan.
Semin Intervent Radiol, 2019 Aug 23; 36(3). PMID: 31435134    Free PMC article.
Review.
CircRNA FGFR3 induces epithelial-mesenchymal transition of ovarian cancer by regulating miR-29a-3p/E2F1 axis.
Jing Zhou, Ze-Ning Dong, +5 authors, Yu-Fang Sun.
Aging (Albany NY), 2020 Jul 16; 12(14). PMID: 32668414    Free PMC article.
Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial.
Frances Humby, Patrick Durez, +28 authors, R4RA collaborative group.
Lancet, 2021 Jan 25; 397(10271). PMID: 33485455    Free PMC article.