The Potential of Tumor Debulking to Support Molecular Targeted Therapies
Tumors may consist of billions of cells, which in malignant cases disseminate and form distant metastases. The large number of tumor cells formed by the high number of cell divisions during tumor progression creates a heterogeneous set of genetically diverse tumor cell clones. For cancer therapy thi...
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Published in | Frontiers in oncology Vol. 10; p. 801 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
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18.06.2020
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Abstract | Tumors may consist of billions of cells, which in malignant cases disseminate and form distant metastases. The large number of tumor cells formed by the high number of cell divisions during tumor progression creates a heterogeneous set of genetically diverse tumor cell clones. For cancer therapy this poses unique challenges, as distinct clones have to be targeted in different tissue locations. Recent research has led to the development of specific inhibitors of defined targets in cellular signaling cascades which promise more effective and more tumor-specific therapy approaches. Many of these molecular targeted therapy (MTT) compounds have already been translated into clinics or are currently being tested in clinical studies. However, the outgrowth of tumor cell clones resistant to such inhibitors is a drawback that affects specific inhibitors in a similar way as classical cytotoxic chemotherapeutics, because additionally acquired genetic alterations can enable tumor cells to circumvent the particular regulators of cellular signaling being targeted. Thus, it might be desirable to reduce genetic heterogeneity prior to molecular targeting, which could reduce the statistical chance of tumor relapse initiated by resistant clones. One way to achieve this is employing unspecific methods to remove as much tumor material as possible before MTT, e.g., by tumor debulking (TD). Currently, this is successfully applied in the clinical treatment of ovarian cancer. We believe that TD followed by treatment with a combination of molecular targeted drugs, optimally guided by biomarkers, might advance survival of patients suffering from various cancer types. |
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AbstractList | Tumors may consist of billions of cells, which in malignant cases disseminate and form distant metastases. The large number of tumor cells formed by the high number of cell divisions during tumor progression creates a heterogeneous set of genetically diverse tumor cell clones. For cancer therapy this poses unique challenges, as distinct clones have to be targeted in different tissue locations. Recent research has led to the development of specific inhibitors of defined targets in cellular signaling cascades which promise more effective and more tumor-specific therapy approaches. Many of these molecular targeted therapy (MTT) compounds have already been translated into clinics or are currently being tested in clinical studies. However, the outgrowth of tumor cell clones resistant to such inhibitors is a drawback that affects specific inhibitors in a similar way as classical cytotoxic chemotherapeutics, because additionally acquired genetic alterations can enable tumor cells to circumvent the particular regulators of cellular signaling being targeted. Thus, it might be desirable to reduce genetic heterogeneity prior to molecular targeting, which could reduce the statistical chance of tumor relapse initiated by resistant clones. One way to achieve this is employing unspecific methods to remove as much tumor material as possible before MTT, e.g., by tumor debulking (TD). Currently, this is successfully applied in the clinical treatment of ovarian cancer. We believe that TD followed by treatment with a combination of molecular targeted drugs, optimally guided by biomarkers, might advance survival of patients suffering from various cancer types. |
Author | Görner, Martin Oppel, Felix Sudhoff, Holger |
AuthorAffiliation | 1 Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld , Bielefeld , Germany 2 Department of Hematology and Oncology, Klinikum Bielefeld , Bielefeld , Germany |
AuthorAffiliation_xml | – name: 2 Department of Hematology and Oncology, Klinikum Bielefeld , Bielefeld , Germany – name: 1 Department of Otolaryngology, Head and Neck Surgery, Klinikum Bielefeld , Bielefeld , Germany |
Author_xml | – sequence: 1 givenname: Felix surname: Oppel fullname: Oppel, Felix – sequence: 2 givenname: Martin surname: Görner fullname: Görner, Martin – sequence: 3 givenname: Holger surname: Sudhoff fullname: Sudhoff, Holger |
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Cites_doi | 10.1038/s41392-019-0095-0 10.1056/NEJMe1500181 10.1158/2159-8290.CD-17-1226 10.3322/canjclin.25.3.152 10.1126/scitranslmed.3007094 10.2147/IJWH.S49781 10.1056/NEJMoa1708539 10.1038/s41392-019-0099-9 10.1038/s41467-017-01174-3 10.1001/archoto.2012.20 10.1186/s13045-019-0818-2 10.1038/ni1102-999 10.1038/nrg2158 10.1158/0008-5472.CAN-05-0328 10.1002/1097-0142(197501)35:1<98::AID-CNCR2820350115>3.0.CO;2-B 10.1038/nature09515 10.1111/nyas.12356 10.1016/S0140-6736(15)60898-4 10.1186/s40661-016-0024-7 10.1016/B978-0-12-397927-8.00011-7 10.1056/NEJMoa1210093 10.1016/j.cell.2017.11.009 10.1056/NEJMoa1911361 10.1111/cas.13763 10.1200/JCO.18.00131 10.1124/mol.115.099325 10.3389/fonc.2019.00268 10.1093/annonc/mdy452 10.3390/cancers10070224 10.1200/EDBK_240837 10.1186/1471-2407-14-969 10.1056/NEJMoa1714448 10.1038/s41591-019-0407-5 10.3390/cancers6031769 10.3892/ol.2018.8300 10.1155/2014/717295 10.1016/j.molmed.2018.12.009 10.1377/hlthaff.2017.1575 10.1093/jnci/djt273 10.1038/nrclinonc.2017.166 10.1056/NEJMoa1113205 10.1038/nrclinonc.2015.175 10.1016/S1470-2045(15)00188-6 10.1097/01.ju.0000110610.61545.ae 10.21037/atm.2018.11.31 10.1038/s41598-020-58674-4 10.1200/JCO.2015.63.2497 10.3389/fmed.2018.00085 10.3322/caac.21492 10.1126/science.959840 10.3389/fonc.2014.00190 10.1158/2159-8290.CD-15-0063 10.1038/s41586-019-1730-1 10.1016/j.molonc.2014.05.004 10.1038/nrclinonc.2017.186 10.1080/14656566.2017.1383384 10.1158/0008-5472.CAN-17-1229 10.1038/bjc.2012.581 10.1056/NEJMoa1103799 10.1038/nature10762 10.1038/s41598-019-52913-z |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Scott Anderw Fisher, University of Western Australia, Australia; Massimo Fantini, Precision Biologics, Inc., United States Edited by: Triantafyllos Stylianopoulos, University of Cyprus, Cyprus This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology |
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References | Brady (B19) 2017; 8 Sato (B41) 2018; 109 Sicklick (B31) 2019; 25 Govindan (B3) 2015; 372 DeVita (B7) 1975; 25 DeVita (B8) 1975; 35 Orbegoso (B48) 2017; 18 Aslam (B46) 2014; 2014 Fares (B44) 2019; 39 Drilon (B36) 2018; 378 Kopetz (B35) 2015; 33 Le Tourneau (B32) 2015; 16 Flaherty (B14) 2012; 367 Hu (B56) 2012; 138 Meehan (B49) 2016; 3 Bray (B1) 2018; 68 Long (B62) 2015; 386 Schrank (B4) 2018; 10 Pennell (B58) 2019; 37 Cheng (B28) 2019; 4 Mouridsen (B6) 1977; 61 Spaans (B5) 2014; 4 Broomfield (B53) 2005; 65 Kozakiewicz (B25) 2018; 15 Galot (B33) 2018; 29 Khong (B54) 2014; 14 Baer (B16) 2007; 8 Tricker (B42) 2015; 5 Groenendijk (B39) 2014; 8 Housman (B21) 2014; 6 Perren (B45) 2011; 365 Flanigan (B52) 2004; 171 Schmitt (B38) 2016; 13 Gerlinger (B20) 2012; 366 Nadauld (B30) 2018; 37 Yachida (B18) 2010; 467 Palmer (B12) 2017; 171 Sun (B29) 2020; 10 Corcoran (B40) 2018; 8 Long (B63) 2017; 377 Brower (B24) 2013; 105 Moscow (B34) 2018; 15 Somasundaram (B9) 2012; 65 Fisher (B22) 2013; 108 Law (B26) 2015; 88 Stanta (B11) 2018; 5 Hacker (B51) 1983; 61 Khong (B43) 2002; 3 Sabnis (B2) 2019; 25 Dagogo-Jack (B13) 2018; 15 Chowell (B23) 2018; 78 Wee (B27) 2014; 1309 Lim (B10) 2019; 12 Nowell (B15) 1976; 194 Greaves (B17) 2012; 481 Bai (B59) 2018; 6 Vasan (B37) 2019; 575 Guisier (B55) 2019; 9 Bettegowda (B60) 2014; 6 Yuan (B57) 2019; 4 Davidson (B47) 2014; 6 Luebker (B61) 2019; 9 Ray-Coquard (B50) 2019; 381 |
References_xml | – volume: 4 start-page: 62 year: 2019 ident: B28 article-title: Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials publication-title: Signal Trans Targeted Ther doi: 10.1038/s41392-019-0095-0 contributor: fullname: Cheng – volume: 372 start-page: 1760 year: 2015 ident: B3 article-title: Overcoming resistance to targeted therapy for lung cancer publication-title: N Engl J Med doi: 10.1056/NEJMe1500181 contributor: fullname: Govindan – volume: 61 start-page: 413 year: 1983 ident: B51 article-title: Primary cytoreductive surgery for epithelial ovarian cancer publication-title: Obstet Gynecol contributor: fullname: Hacker – volume: 8 start-page: 428 year: 2018 ident: B40 article-title: Combined BRAF, EGFR, and MEK inhibition in patients with BRAF(V600E)-mutant colorectal cancer publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-17-1226 contributor: fullname: Corcoran – volume: 25 start-page: 152 year: 1975 ident: B7 article-title: Single agent versus combination chemotherapy publication-title: CA Cancer J Clin doi: 10.3322/canjclin.25.3.152 contributor: fullname: DeVita – volume: 6 start-page: 224ra24 year: 2014 ident: B60 article-title: Detection of circulating tumor DNA in early- and late-stage human malignancies publication-title: Sci Transl Med doi: 10.1126/scitranslmed.3007094 contributor: fullname: Bettegowda – volume: 6 start-page: 289 year: 2014 ident: B47 article-title: Profile of pazopanib and its potential in the treatment of epithelial ovarian cancer publication-title: Int J Women's Health doi: 10.2147/IJWH.S49781 contributor: fullname: Davidson – volume: 377 start-page: 1813 year: 2017 ident: B63 article-title: Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma publication-title: N Engl J Med doi: 10.1056/NEJMoa1708539 contributor: fullname: Long – volume: 4 start-page: 61 year: 2019 ident: B57 article-title: The emerging treatment landscape of targeted therapy in non-small-cell lung cancer publication-title: Signal Trans Targeted Ther doi: 10.1038/s41392-019-0099-9 contributor: fullname: Yuan – volume: 8 start-page: 1231 year: 2017 ident: B19 article-title: Combating subclonal evolution of resistant cancer phenotypes publication-title: Nat Commun doi: 10.1038/s41467-017-01174-3 contributor: fullname: Brady – volume: 138 start-page: 412 year: 2012 ident: B56 article-title: A novel modular polymer platform for the treatment of head and neck squamous cell carcinoma in an animal model publication-title: Arch Otolaryngol Head Neck Surg doi: 10.1001/archoto.2012.20 contributor: fullname: Hu – volume: 12 start-page: 134 year: 2019 ident: B10 article-title: Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy publication-title: J Hematol Oncol doi: 10.1186/s13045-019-0818-2 contributor: fullname: Lim – volume: 3 start-page: 999 year: 2002 ident: B43 article-title: Natural selection of tumor variants in the generation of “tumor escape” phenotypes publication-title: Nat Immunol doi: 10.1038/ni1102-999 contributor: fullname: Khong – volume: 8 start-page: 619 year: 2007 ident: B16 article-title: Mutation rate variation in multicellular eukaryotes: causes and consequences publication-title: Nat Rev Genet doi: 10.1038/nrg2158 contributor: fullname: Baer – volume: 65 start-page: 7580 year: 2005 ident: B53 article-title: Partial, but not complete, tumor-debulking surgery promotes protective antitumor memory when combined with chemotherapy and adjuvant immunotherapy publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-05-0328 contributor: fullname: Broomfield – volume: 35 start-page: 98 year: 1975 ident: B8 article-title: Combination versus single agent chemotherapy: a review of the basis for selection of drug treatment of cancer publication-title: Cancer doi: 10.1002/1097-0142(197501)35:1<98::AID-CNCR2820350115>3.0.CO;2-B contributor: fullname: DeVita – volume: 467 start-page: 1114 year: 2010 ident: B18 article-title: Distant metastasis occurs late during the genetic evolution of pancreatic cancer publication-title: Nature doi: 10.1038/nature09515 contributor: fullname: Yachida – volume: 1309 start-page: 30 year: 2014 ident: B27 article-title: Targeting epigenetic regulators for cancer therapy publication-title: Ann N Y Acad Sci doi: 10.1111/nyas.12356 contributor: fullname: Wee – volume: 386 start-page: 444 year: 2015 ident: B62 article-title: Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial publication-title: Lancet doi: 10.1016/S0140-6736(15)60898-4 contributor: fullname: Long – volume: 3 start-page: 3 year: 2016 ident: B49 article-title: New treatment option for ovarian cancer: PARP inhibitors publication-title: Gynecol Oncol Res Pract doi: 10.1186/s40661-016-0024-7 contributor: fullname: Meehan – volume: 65 start-page: 335 year: 2012 ident: B9 article-title: Intratumoral heterogeneity as a therapy resistance mechanism: role of melanoma subpopulations publication-title: Adv Pharmacol doi: 10.1016/B978-0-12-397927-8.00011-7 contributor: fullname: Somasundaram – volume: 367 start-page: 1694 year: 2012 ident: B14 article-title: Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations publication-title: N Engl J Med doi: 10.1056/NEJMoa1210093 contributor: fullname: Flaherty – volume: 171 start-page: 1678 year: 2017 ident: B12 article-title: Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy publication-title: Cell doi: 10.1016/j.cell.2017.11.009 contributor: fullname: Palmer – volume: 381 start-page: 2416 year: 2019 ident: B50 article-title: Olaparib plus bevacizumab as first-line maintenance in ovarian cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1911361 contributor: fullname: Ray-Coquard – volume: 109 start-page: 3183 year: 2018 ident: B41 article-title: Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer publication-title: Cancer Sci doi: 10.1111/cas.13763 contributor: fullname: Sato – volume: 37 start-page: 97 year: 2019 ident: B58 article-title: SELECT: a phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small-cell lung cancer publication-title: J Clin Oncol doi: 10.1200/JCO.18.00131 contributor: fullname: Pennell – volume: 88 start-page: 846 year: 2015 ident: B26 article-title: Cyclin-dependent kinase inhibitors as anticancer therapeutics publication-title: Mol Pharmacol doi: 10.1124/mol.115.099325 contributor: fullname: Law – volume: 9 start-page: 268 year: 2019 ident: B61 article-title: Diverse mechanisms of BRAF inhibitor resistance in melanoma identified in clinical and preclinical studies publication-title: Front Oncol doi: 10.3389/fonc.2019.00268 contributor: fullname: Luebker – volume: 29 start-page: 2313 year: 2018 ident: B33 article-title: Personalized biomarker-based treatment strategy for patients with squamous cell carcinoma of the head and neck: EORTC position and approach publication-title: Ann Oncol doi: 10.1093/annonc/mdy452 contributor: fullname: Galot – volume: 10 start-page: 224 year: 2018 ident: B4 article-title: Current molecular-targeted therapies in NSCLC and their mechanism of resistance publication-title: Cancers. doi: 10.3390/cancers10070224 contributor: fullname: Schrank – volume: 39 start-page: 147 year: 2019 ident: B44 article-title: Mechanisms of resistance to immune checkpoint blockade: why does checkpoint inhibitor immunotherapy not work for all patients? publication-title: Am Soc Clin Oncol Educ Book. doi: 10.1200/EDBK_240837 contributor: fullname: Fares – volume: 14 start-page: 969 year: 2014 ident: B54 article-title: The efficacy of tumor debulking surgery is improved by adjuvant immunotherapy using imiquimod and anti-CD40 publication-title: BMC Cancer doi: 10.1186/1471-2407-14-969 contributor: fullname: Khong – volume: 378 start-page: 731 year: 2018 ident: B36 article-title: Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children publication-title: N Engl J Med doi: 10.1056/NEJMoa1714448 contributor: fullname: Drilon – volume: 25 start-page: 744 year: 2019 ident: B31 article-title: Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study publication-title: Nat Med doi: 10.1038/s41591-019-0407-5 contributor: fullname: Sicklick – volume: 6 start-page: 1769 year: 2014 ident: B21 article-title: Drug resistance in cancer: an overview publication-title: Cancers doi: 10.3390/cancers6031769 contributor: fullname: Housman – volume: 15 start-page: 7497 year: 2018 ident: B25 article-title: Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma publication-title: Oncol Lett doi: 10.3892/ol.2018.8300 contributor: fullname: Kozakiewicz – volume: 2014 start-page: 717295 year: 2014 ident: B46 article-title: Cytoreductive nephrectomy for metastatic renal cell carcinoma: a review of the historical literature and its role in the era of targeted molecular therapy publication-title: ISRN Urol doi: 10.1155/2014/717295 contributor: fullname: Aslam – volume: 25 start-page: 185 year: 2019 ident: B2 article-title: Principles of resistance to targeted cancer therapy: lessons from basic and translational cancer biology publication-title: Trends Mol Med doi: 10.1016/j.molmed.2018.12.009 contributor: fullname: Sabnis – volume: 37 start-page: 751 year: 2018 ident: B30 article-title: Strategies for clinical implementation: precision oncology at three distinct institutions publication-title: Health Aff doi: 10.1377/hlthaff.2017.1575 contributor: fullname: Nadauld – volume: 105 start-page: 1421 year: 2013 ident: B24 article-title: Tracking chemotherapy's effects on secondary cancers publication-title: J Natl Cancer Inst doi: 10.1093/jnci/djt273 contributor: fullname: Brower – volume: 15 start-page: 81 year: 2018 ident: B13 article-title: Tumour heterogeneity and resistance to cancer therapies publication-title: Nat Rev. Clin Oncol doi: 10.1038/nrclinonc.2017.166 contributor: fullname: Dagogo-Jack – volume: 366 start-page: 883 year: 2012 ident: B20 article-title: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing publication-title: N Engl J Med doi: 10.1056/NEJMoa1113205 contributor: fullname: Gerlinger – volume: 13 start-page: 335 year: 2016 ident: B38 article-title: The influence of subclonal resistance mutations on targeted cancer therapy publication-title: Nat Rev Clin Oncol doi: 10.1038/nrclinonc.2015.175 contributor: fullname: Schmitt – volume: 16 start-page: 1324 year: 2015 ident: B32 article-title: investigators, molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial publication-title: Lancet Oncol doi: 10.1016/S1470-2045(15)00188-6 contributor: fullname: Le Tourneau – volume: 171 start-page: 1071 year: 2004 ident: B52 article-title: Cytoreductive nephrectomy in patients with metastatic renal cancer: a combined analysis publication-title: J Urol doi: 10.1097/01.ju.0000110610.61545.ae contributor: fullname: Flanigan – volume: 6 start-page: S89 year: 2018 ident: B59 article-title: Liquid biopsy in tumors: opportunities and challenges publication-title: Ann Transl Med doi: 10.21037/atm.2018.11.31 contributor: fullname: Bai – volume: 10 start-page: 2083 year: 2020 ident: B29 article-title: Clinical efficacy and safety of anti-PD-1/PD-L1 inhibitors for the treatment of advanced or metastatic cancer: a systematic review and meta-analysis publication-title: Sci Rep doi: 10.1038/s41598-020-58674-4 contributor: fullname: Sun – volume: 33 start-page: 4032 year: 2015 ident: B35 article-title: Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer publication-title: J Clin Oncol doi: 10.1200/JCO.2015.63.2497 contributor: fullname: Kopetz – volume: 61 start-page: 47 year: 1977 ident: B6 article-title: Evaluation of single-drug versus multiple-drug chemotherapy in the treatment of advanced breast cancer publication-title: Cancer Treat Rep contributor: fullname: Mouridsen – volume: 5 start-page: 85 year: 2018 ident: B11 article-title: Overview on clinical relevance of intra-tumor heterogeneity publication-title: Front Med doi: 10.3389/fmed.2018.00085 contributor: fullname: Stanta – volume: 68 start-page: 394 year: 2018 ident: B1 article-title: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries publication-title: CA Cancer J Clin doi: 10.3322/caac.21492 contributor: fullname: Bray – volume: 194 start-page: 23 year: 1976 ident: B15 article-title: The clonal evolution of tumor cell populations publication-title: Science doi: 10.1126/science.959840 contributor: fullname: Nowell – volume: 4 start-page: 190 year: 2014 ident: B5 article-title: Drug resistance to molecular targeted therapy and its consequences for treatment decisions in non-small-cell lung cancer publication-title: Front Oncol doi: 10.3389/fonc.2014.00190 contributor: fullname: Spaans – volume: 5 start-page: 960 year: 2015 ident: B42 article-title: Combined EGFR/MEK inhibition prevents the emergence of resistance in EGFR-mutant lung cancer publication-title: Cancer Discov doi: 10.1158/2159-8290.CD-15-0063 contributor: fullname: Tricker – volume: 575 start-page: 299 year: 2019 ident: B37 article-title: A view on drug resistance in cancer publication-title: Nature doi: 10.1038/s41586-019-1730-1 contributor: fullname: Vasan – volume: 8 start-page: 1067 year: 2014 ident: B39 article-title: Drug resistance to targeted therapies: deja vu all over again publication-title: Mol Oncol doi: 10.1016/j.molonc.2014.05.004 contributor: fullname: Groenendijk – volume: 15 start-page: 183 year: 2018 ident: B34 article-title: The evidence framework for precision cancer medicine publication-title: Nat Rev Clin Oncol doi: 10.1038/nrclinonc.2017.186 contributor: fullname: Moscow – volume: 18 start-page: 1637 year: 2017 ident: B48 article-title: The role of cediranib in ovarian cancer publication-title: Expert Opin Pharmacother doi: 10.1080/14656566.2017.1383384 contributor: fullname: Orbegoso – volume: 78 start-page: 830 year: 2018 ident: B23 article-title: Modeling the subclonal evolution of cancer cell populations publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-17-1229 contributor: fullname: Chowell – volume: 108 start-page: 479 year: 2013 ident: B22 article-title: Cancer heterogeneity: implications for targeted therapeutics publication-title: Br J Cancer doi: 10.1038/bjc.2012.581 contributor: fullname: Fisher – volume: 365 start-page: 2484 year: 2011 ident: B45 article-title: A phase 3 trial of bevacizumab in ovarian cancer publication-title: N Engl J Med doi: 10.1056/NEJMoa1103799 contributor: fullname: Perren – volume: 481 start-page: 306 year: 2012 ident: B17 article-title: Clonal evolution in cancer publication-title: Nature doi: 10.1038/nature10762 contributor: fullname: Greaves – volume: 9 start-page: 16902 year: 2019 ident: B55 article-title: A rationale for surgical debulking to improve anti-PD1 therapy outcome in non small cell lung cancer publication-title: Sci Rep doi: 10.1038/s41598-019-52913-z contributor: fullname: Guisier |
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Snippet | Tumors may consist of billions of cells, which in malignant cases disseminate and form distant metastases. The large number of tumor cells formed by the high... |
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SubjectTerms | cancer genetics cancer therapy clonal heterogeneity molecular targeting Oncology precision oncology therapy resistance |
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Title | The Potential of Tumor Debulking to Support Molecular Targeted Therapies |
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