Abstract
Original language | English |
---|---|
Journal | Journal of Experimental and Clinical Cancer Research |
Volume | 37 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2018 |
Keywords
- Patient-derived xenografts
- Renal cell carcinoma
- Reverse phase protein array; personalized therapy
- Targeted therapy
- mammalian target of rapamycin
- sunitinib
- tumor marker
- angiogenesis
- animal cell
- animal experiment
- animal model
- animal tissue
- Article
- cancer grading
- cancer prognosis
- cancer recurrence
- cancer staging
- controlled study
- drug screening
- epithelium cell
- human
- human cell
- human tissue
- immune deficiency
- in vitro study
- in vivo study
- male
- medical decision making
- mesenchymal stem cell
- mouse
- mTOR signaling
- nephrectomy
- nonhuman
- patient care
- personalized medicine
- phenotype
- priority journal
- protein microarray
- protein phosphorylation
- renal cell carcinoma
- therapy effect
- tissue section
- tumor engraftment
- tumor xenograft
- animal
- cell lineage
- disease model
- genetics
- kidney tumor
- pathology
- prognosis
- tumor recurrence
- Animals
- Biomarkers, Tumor
- Cell Lineage
- Disease Models, Animal
- Humans
- Kidney Neoplasms
- Mice
- Neoplasm Recurrence, Local
- Precision Medicine
- Prognosis
- Xenograft Model Antitumor Assays
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Renal cancer: New models and approach for personalizing therapy. / Di Martino, S.; De Luca, G.; Grassi, L.; Federici, G.; Alfonsi, R.; Signore, M.; Addario, A.; De Salvo, L.; Francescangeli, F.; Sanchez, M.; Tirelli, V.; Muto, G.; Sperduti, I.; Sentinelli, S.; Costantini, M.; Pasquini, L.; Milella, M.; Haoui, M.; Simone, G.; Gallucci, M.; De Maria, R.; Bonci, D.
In: Journal of Experimental and Clinical Cancer Research, Vol. 37, No. 1, 2018.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Renal cancer: New models and approach for personalizing therapy
AU - Di Martino, S.
AU - De Luca, G.
AU - Grassi, L.
AU - Federici, G.
AU - Alfonsi, R.
AU - Signore, M.
AU - Addario, A.
AU - De Salvo, L.
AU - Francescangeli, F.
AU - Sanchez, M.
AU - Tirelli, V.
AU - Muto, G.
AU - Sperduti, I.
AU - Sentinelli, S.
AU - Costantini, M.
AU - Pasquini, L.
AU - Milella, M.
AU - Haoui, M.
AU - Simone, G.
AU - Gallucci, M.
AU - De Maria, R.
AU - Bonci, D.
N1 - Cited By :1 Export Date: 11 April 2019 CODEN: JECRD Correspondence Address: De Maria, R.; Institute of General Pathology, Fondazione Policlinico Universitario, A. Gemelli e Università CattolicaItaly; email: ruggero.demaria@unicatt.it Chemicals/CAS: sunitinib, 341031-54-7, 557795-19-4; Biomarkers, Tumor Funding details: 15ONC/1 Funding text 1: The present study was supported by: National Ministry of Health, Oncotecnologico program 15ONC/1 to DB, TRANSCAN-2-JTC (2016) to DB, Ricerca corrente 2017 to Istituto Superiore di Sanità and “Ricerca Corrente 2015-2016” Regina Elena, IRE/IFO to DB, RDM and MG. References: Shuch, B., Amin, A., Armstrong, A.J., Eble, J.N., Ficarra, V., Lopez-Beltran, A., Understanding pathologic variants of renal cell carcinoma: Distilling therapeutic opportunities from biologic complexity (2015) Eur Urol, 67 (1), pp. 85-97. , 24857407 Epub 2014/05/27; Leibovich, B.C., Han, K.R., Bui, M.H., Pantuck, A.J., Dorey, F.J., Figlin, R.A., Scoring algorithm to predict survival after nephrectomy and immunotherapy in patients with metastatic renal cell carcinoma: A stratification tool for prospective clinical trials (2003) Cancer, 98 (12), pp. 2566-2575. , 14669275 Epub 2003/12/12; Motzer, R.J., Escudier, B., McDermott, D.F., George, S., Hammers, H.J., Srinivas, S., Nivolumab versus Everolimus in advanced renal-cell carcinoma (2015) N Engl J Med, 373 (19), pp. 1803-1813. , 26406148 5719487; Anandappa, G., Hollingdale, A., Eisen, T., Everolimus - A new approach in the treatment of renal cell carcinoma (2010) Cancer Manag Res, 2, pp. 61-70. , 21188097 3004583; Wullschleger, S., Loewith, R., Hall, M.N., TOR signaling in growth and metabolism (2006) Cell, 124 (3), pp. 471-484. , 16469695; Weis, S.M., Cheresh, D.A., Tumor angiogenesis: Molecular pathways and therapeutic targets (2011) Nat Med, 17 (11), pp. 1359-1370. , 22064426; Potente, M., Gerhardt, H., Carmeliet, P., Basic and therapeutic aspects of angiogenesis (2011) Cell, 146 (6), pp. 873-887. , 21925313; Gupta, S., Spiess, P.E., The prospects of pazopanib in advanced renal cell carcinoma (2013) Ther Adv Urol, 5 (5), pp. 223-232. , 24082917 3763778; Guertin, D.A., Sabatini, D.M., The pharmacology of mTOR inhibition (2009) Sci Signal, 2 (67), p. pe24. , 19383975; Battelli, C., Cho, D.C., MTOR inhibitors in renal cell carcinoma (2011) Therapy, 8 (4), pp. 359-367. , 21894244 3164983; Heng, D.Y., Xie, W., Regan, M.M., Warren, M.A., Golshayan, A.R., Sahi, C., Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: Results from a large, multicenter study (2009) J Clin Oncol, 27 (34), pp. 5794-5799. , 19826129; Gerlinger, M., Catto, J.W., Orntoft, T.F., Real, F.X., Zwarthoff, E.C., Swanton, C., Intratumour heterogeneity in urologic cancers: From molecular evidence to clinical implications (2015) Eur Urol, 67 (4), pp. 729-737. , 24836153; Albiges, L., Kube, U., Eymard, J.C., Schmidinger, M., Bamias, A., Kelkouli, N., Everolimus for patients with metastatic renal cell carcinoma refractory to anti-VEGF therapy: Results of a pooled analysis of non-interventional studies (2015) Eur J Cancer, 51 (16), pp. 2368-2374. , 26276039; Clevers, H., Modeling development and disease with organoids (2016) Cell, 165 (7), pp. 1586-1597. , 27315476; Clevers, H., The cancer stem cell: Premises, promises and challenges (2011) Nat Med, 17 (3), pp. 313-319. , 21386835 Epub 2011/03/10; Sato, T., Clevers, H., Growing self-organizing mini-guts from a single intestinal stem cell: Mechanism and applications (2013) Science, 340 (6137), pp. 1190-1194. , 23744940 Epub 2013/06/08; Sachs, N., Clevers, H., Organoid cultures for the analysis of cancer phenotypes (2014) Curr Opin Genet Dev, 24, pp. 68-73. , 24657539 Epub 2014/03/25; Gao, D., Vela, I., Sboner, A., Iaquinta, P.J., Karthaus, W.R., Gopalan, A., Organoid cultures derived from patients with advanced prostate cancer (2014) Cell, 159 (1), pp. 176-187. , 25201530 4237931 Epub 2014/09/10; Amirouchene-Angelozzi, N., Swanton, C., Bardelli, A., Tumor evolution as a therapeutic target (2017) Cancer Discov, 7 (8), pp. 1-13. , Epub 2017/07/22; McGranahan, N., Swanton, C., Clonal heterogeneity and tumor evolution: Past, present, and the future (2017) Cell, 168 (4), pp. 613-628. , 28187284 Epub 2017/02/12; Adelaiye, R., Ciamporcero, E., Miles, K.M., Sotomayor, P., Bard, J., Tsompana, M., Sunitinib dose escalation overcomes transient resistance in clear cell renal cell carcinoma and is associated with epigenetic modifications (2015) Mol Cancer Ther, 14 (2), pp. 513-522. , 25519701 Epub 2014/12/19; Bieche, I., Vacher, S., Vallerand, D., Richon, S., Hatem, R., De Plater, L., Vasculature analysis of patient derived tumor xenografts using species-specific PCR assays: Evidence of tumor endothelial cells and atypical VEGFA-VEGFR1/2 signalings (2014) BMC Cancer, 14, p. 178. , 24625025 4007753 Epub 2014/03/15; Jimenez-Valerio, G., Martinez-Lozano, M., Bassani, N., Vidal, A., Ochoa-De-Olza, M., Suarez, C., Resistance to antiangiogenic therapies by metabolic Symbiosis in renal cell carcinoma PDX models and patients (2016) Cell Rep, 15 (6), pp. 1134-1143. , 27134180 4870515 Epub 2016/05/03; Karam, J.A., Zhang, X.Y., Tamboli, P., Margulis, V., Wang, H., Abel, E.J., Development and characterization of clinically relevant tumor models from patients with renal cell carcinoma (2011) Eur Urol, 59 (4), pp. 619-628. , 21167632 Epub 2010/12/21; Schuller, A.G., Barry, E.R., Jones, R.D., Henry, R.E., Frigault, M.M., Beran, G., The MET inhibitor AZD6094 (Savolitinib, HMPL-504) induces regression in papillary renal cell carcinoma patient-derived xenograft models (2015) Clin Cancer Res, 21 (12), pp. 2811-2819. , 25779944 Epub 2015/03/18; Sivanand, S., Pena-Llopis, S., Zhao, H., Kucejova, B., Spence, P., Pavia-Jimenez, A., A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma (2012) Sci Transl Med, 4 (137), p. 137ra75. , 22674553 3570965 Epub 2012/06/08; Tentler, J.J., Tan, A.C., Weekes, C.D., Jimeno, A., Leong, S., Pitts, T.M., Patient-derived tumour xenografts as models for oncology drug development (2012) Nat Rev Clin Oncol, 9 (6), pp. 338-350. , 22508028 3928688; Thong, A.E., Zhao, H., Ingels, A., Valta, M.P., Nolley, R., Santos, J., Tissue slice grafts of human renal cell carcinoma: An authentic preclinical model with high engraftment rate and metastatic potential (2014) Urol Oncol, 32 (1), p. 43. , Epub 2013/08/06 e23-43 e30; Vanmeter, A., Signore, M., Pierobon, M., Espina, V., Liotta, L.A., Petricoin, E.F., 3rd, Reverse-phase protein microarrays: Application to biomarker discovery and translational medicine (2007) Expert Rev Mol Diagn, 7 (5), pp. 625-633. , 17892368; Bonci, D., Coppola, V., Patrizii, M., Addario, A., Cannistraci, A., Francescangeli, F., A microRNA code for prostate cancer metastasis (2016) Oncogene, 35 (9), pp. 1180-1192. , 26073083 Epub 2015/06/16; Bonci, D., Coppola, V., Musumeci, M., Addario, A., Giuffrida, R., Memeo, L., The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities (2008) Nat Med, 14 (11), pp. 1271-1277. , 18931683 Epub 2008/10/22; Cannistraci, A., Federici, G., Addario, A., Di Pace, A.L., Grassi, L., Muto, G., C-met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition (2017) Oncogene, 36 (26), pp. 3718-3728. , 28192399 Epub 2017/02/14; Zabouo, G., Imbert, A.M., Jacquemier, J., Finetti, P., Moreau, T., Esterni, B., CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines (2009) Breast Cancer Res, 11 (1), p. R1. , 19123925 2687703; Nodomi, S., Umeda, K., Saida, S., Kinehara, T., Hamabata, T., Daifu, T., CD146 is a novel marker for highly tumorigenic cells and a potential therapeutic target in malignant rhabdoid tumor (2016) Oncogene, 35 (40), pp. 5317-5327. , 27041577 5057042; Feng, G., Fang, F., Liu, C., Zhang, F., Huang, H., Pu, C., CD146 gene expression in clear cell renal cell carcinoma: A potential marker for prediction of early recurrence after nephrectomy (2012) Int Urol Nephrol, 44 (6), pp. 1663-1669. , 22826148; Escudier, B., Porta, C., Schmidinger, M., Algaba, F., Patard, J.J., Khoo, V., Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up (2014) Ann Oncol, 25 (3), pp. iii49-iii56. , 25210086 Epub 2014/09/12; Schodel, J., Grampp, S., Maher, E.R., Moch, H., Ratcliffe, P.J., Russo, P., Hypoxia, hypoxia-inducible transcription factors, and renal Cancer (2016) Eur Urol, 69 (4), pp. 646-657. , 26298207; Masoud, G.N., Li, W., HIF-1alpha pathway: Role, regulation and intervention for cancer therapy (2015) Acta Pharm Sin B, 5 (5), pp. 378-389. , 26579469 4629436; Ravaud, A., Motzer, R.J., Pandha, H.S., George, D.J., Pantuck, A.J., Patel, A., Adjuvant Sunitinib in high-risk renal-cell carcinoma after nephrectomy (2016) N Engl J Med, 375 (23), pp. 2246-2254. , 27718781; Janowitz, T., Welsh, S.J., Zaki, K., Mulders, P., Eisen, T., Adjuvant therapy in renal cell carcinoma-past, present, and future (2013) Semin Oncol, 40 (4), pp. 482-491. , 23972712 3765962; Mentrikoski, M.J., Wendroth, S.M., Wick, M.R., Immunohistochemical distinction of renal cell carcinoma from other carcinomas with clear-cell histomorphology: Utility of CD10 and CA-125 in addition to PAX-2, PAX-8, RCCma, and adipophilin (2014) Appl Immunohistochem Mol Morphol, 22 (9), pp. 635-641. , 25279712; Barr, M.L., Jilaveanu, L.B., Camp, R.L., Adeniran, A.J., Kluger, H.M., Shuch, B., PAX-8 expression in renal tumours and distant sites: A useful marker of primary and metastatic renal cell carcinoma? (2015) J Clin Pathol, 68 (1), pp. 12-17. , 25315900 Epub 2014/10/16; Gerlinger, M., Rowan, A.J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Intratumor heterogeneity and branched evolution revealed by multiregion sequencing (2012) N Engl J Med, 366 (10), pp. 883-892. , 22397650 4878653; Ferlay, J., Steliarova-Foucher, E., Lortet-Tieulent, J., Rosso, S., Coebergh, J.W., Comber, H., Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012 (2013) Eur J Cancer, 49 (6), pp. 1374-1403. , 23485231; Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 (2015) Int J Cancer, 136 (5), pp. E359-E386. , 25220842
PY - 2018
Y1 - 2018
N2 - Background: Clear cell RCC (ccRCC) accounts for approximately 75% of the renal cancer cases. Surgery treatment seems to be the best efficacious approach for the majority of patients. However, a consistent fraction (30%) of cases progress after surgery with curative intent. It is currently largely debated the use of adjuvant therapy for high-risk patients and the clinical and molecular parameters for stratifying beneficiary categories. In addition, the treatment of advanced forms lacks reliable driver biomarkers for the appropriated therapeutic choice. Thus, renal cancer patient management urges predictive molecular indicators and models for therapy-decision making. Methods: Here, we developed and optimized new models and tools for ameliorating renal cancer patient management. We isolated from fresh tumor specimens heterogeneous multi-clonal populations showing epithelial and mesenchymal characteristics coupled to stem cell phenotype. These cells retained long lasting-tumor-propagating capacity provided a therapy monitoring approach in vitro and in vivo while being able to form parental tumors when orthotopically injected and serially transplanted in immunocompromised murine hosts. Results: In line with recent evidence of multiclonal cancer composition, we optimized in vitro cultures enriched of multiple tumor-propagating populations. Orthotopic xenograft masses recapitulated morphology, grading and malignancy of parental cancers. High-grade but not the low-grade neoplasias, resulted in efficient serial transplantation in mice. Engraftment capacity paralleled grading and recurrence frequency advocating for a prognostic value of our developed model system. Therefore, in search of novel molecular indicators for therapy decision-making, we used Reverse-Phase Protein Arrays (RPPA) to analyze a panel of total and phosphorylated proteins in the isolated populations. Tumor-propagating cells showed several deregulated kinase cascades associated with grading, including angiogenesis and m-TOR pathways. Conclusions: In the era of personalized therapy, the analysis of tumor propagating cells may help improve prediction of disease progression and therapy assignment. The possibility to test pharmacological response of ccRCC stem-like cells in vitro and in orthotopic models may help define a pharmacological profiling for future development of more effective therapies. Likewise, RPPA screening on patient-derived populations offers innovative approach for possible prediction of therapy response. © 2018 The Author(s).
AB - Background: Clear cell RCC (ccRCC) accounts for approximately 75% of the renal cancer cases. Surgery treatment seems to be the best efficacious approach for the majority of patients. However, a consistent fraction (30%) of cases progress after surgery with curative intent. It is currently largely debated the use of adjuvant therapy for high-risk patients and the clinical and molecular parameters for stratifying beneficiary categories. In addition, the treatment of advanced forms lacks reliable driver biomarkers for the appropriated therapeutic choice. Thus, renal cancer patient management urges predictive molecular indicators and models for therapy-decision making. Methods: Here, we developed and optimized new models and tools for ameliorating renal cancer patient management. We isolated from fresh tumor specimens heterogeneous multi-clonal populations showing epithelial and mesenchymal characteristics coupled to stem cell phenotype. These cells retained long lasting-tumor-propagating capacity provided a therapy monitoring approach in vitro and in vivo while being able to form parental tumors when orthotopically injected and serially transplanted in immunocompromised murine hosts. Results: In line with recent evidence of multiclonal cancer composition, we optimized in vitro cultures enriched of multiple tumor-propagating populations. Orthotopic xenograft masses recapitulated morphology, grading and malignancy of parental cancers. High-grade but not the low-grade neoplasias, resulted in efficient serial transplantation in mice. Engraftment capacity paralleled grading and recurrence frequency advocating for a prognostic value of our developed model system. Therefore, in search of novel molecular indicators for therapy decision-making, we used Reverse-Phase Protein Arrays (RPPA) to analyze a panel of total and phosphorylated proteins in the isolated populations. Tumor-propagating cells showed several deregulated kinase cascades associated with grading, including angiogenesis and m-TOR pathways. Conclusions: In the era of personalized therapy, the analysis of tumor propagating cells may help improve prediction of disease progression and therapy assignment. The possibility to test pharmacological response of ccRCC stem-like cells in vitro and in orthotopic models may help define a pharmacological profiling for future development of more effective therapies. Likewise, RPPA screening on patient-derived populations offers innovative approach for possible prediction of therapy response. © 2018 The Author(s).
KW - Patient-derived xenografts
KW - Renal cell carcinoma
KW - Reverse phase protein array; personalized therapy
KW - Targeted therapy
KW - mammalian target of rapamycin
KW - sunitinib
KW - tumor marker
KW - angiogenesis
KW - animal cell
KW - animal experiment
KW - animal model
KW - animal tissue
KW - Article
KW - cancer grading
KW - cancer prognosis
KW - cancer recurrence
KW - cancer staging
KW - controlled study
KW - drug screening
KW - epithelium cell
KW - human
KW - human cell
KW - human tissue
KW - immune deficiency
KW - in vitro study
KW - in vivo study
KW - male
KW - medical decision making
KW - mesenchymal stem cell
KW - mouse
KW - mTOR signaling
KW - nephrectomy
KW - nonhuman
KW - patient care
KW - personalized medicine
KW - phenotype
KW - priority journal
KW - protein microarray
KW - protein phosphorylation
KW - renal cell carcinoma
KW - therapy effect
KW - tissue section
KW - tumor engraftment
KW - tumor xenograft
KW - animal
KW - cell lineage
KW - disease model
KW - genetics
KW - kidney tumor
KW - pathology
KW - prognosis
KW - tumor recurrence
KW - Animals
KW - Biomarkers, Tumor
KW - Cell Lineage
KW - Disease Models, Animal
KW - Humans
KW - Kidney Neoplasms
KW - Mice
KW - Neoplasm Recurrence, Local
KW - Precision Medicine
KW - Prognosis
KW - Xenograft Model Antitumor Assays
U2 - 10.1186/s13046-018-0874-4
DO - 10.1186/s13046-018-0874-4
M3 - Article
VL - 37
JO - Journal of Experimental and Clinical Cancer Research
JF - Journal of Experimental and Clinical Cancer Research
SN - 0392-9078
IS - 1
ER -