Cited by 191Colorectal Cancer Treatments and StudiesPI3K/AKT/mTOR signaling in cancerMelanoma and MAPK Pathways

The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

Inhibition of MEK and PI3K/mTOR Suppresses Tumor Growth but Does Not Cause Tumor Regression in Patient-Derived Xenografts of RAS-Mutant Colorectal Carcinomas

Open access

Migliardi, Giorgia, Sassi, Francesco, Torti, Davide, Galimi, Francesco, Zanella, Eugenia R., Buscarino, Michela, Ribero, Dario, Muratore, Andrea, Massucco, Paolo, Pisacane, Alberto, Risio, Mauro, Capussotti, Lorenzo, Marsoni, Silvia, Di Nicolantonio, Federica, Bardelli, Alberto, Comoglio, Paolo M., Trusolino, Livio, Bertotti, Andrea·2012·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-11-2683

Published version of a preprint

Open this paper in CoChat — free account Open PDF

Abstract

Purpose: Gene mutations along the Ras pathway (KRAS, NRAS, BRAF, PIK3CA) occur in approximately 50% of colorectal cancers (CRC) and correlate with poor response to anti–EGF receptor (EGFR) therapies. We assessed the effects of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) and phosphoinositide 3-kinase (PI3K)/mTOR inhibitors, which neutralize the major Ras effectors, in patient-derived xenografts from RAS/RAF/PIK3CA-mutant metastatic CRCs (mCRC). Experimental Design: Forty mCRC specimens harboring KRAS, NRAS, BRAF, and/or PIK3CA mutations were implanted in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Each xenograft was expanded into four treatment arms: placebo, the MEK inhibitor AZD6244, the PI3K/mTOR inhibitor, BEZ235, or AZD6244 + BEZ235. Cases initially treated with placebo crossed over to AZD6244, BEZ235, and the anti-EGFR monoclonal antibody cetuximab. Results: At the 3-week evaluation time point, cotreatment of established tumors with AZD6244 + BEZ235 induced disease stabilization in the majority of cases (70%) but did not lead to overt tumor regression. Monotherapy was less effective, with BEZ235 displaying higher activity than AZD6244 (disease control rates, DCRs: AZD6244, 27.5%; BEZ235, 42.5%). Triple therapy with cetuximab provided further advantage (DCR, 88%). The extent of disease control declined at the 6-week evaluation time point (DCRs: AZD6244, 13.9%; BEZ235, 16.2%; AZD6244 + BEZ235, 34%). Cross-analysis of mice harboring xenografts from the same original tumor and treated with each of the different modalities revealed subgroups with preferential sensitivity to AZD6244 (12.5%), BEZ235 (35%), or AZD6244 + BEZ235 (42.5%); another subgroup (10%) showed equivalent response to any treatment. Conclusions: The prevalent growth-suppressive effects produced by MEK and PI3K/mTOR inhibition suggest that this strategy may retard disease progression in patients. However, data offer cautionary evidence against the occurrence of durable responses. Clin Cancer Res; 18(9); 2515–25. ©2012 AACR.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1158/1078-0432.ccr-11-2683

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cetuximab and Chemotherapy as Initial Treatment for Metastatic Colorectal Cancer
Van Cutsem, E., Köhne, C.-H., Hitre, E., Zaluski, J., Chang Chien, C.-R., Makhson, A., D'Haens, G., Pintér, T., Lim, R., Bodoky, G., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0805019 · Cited by 3,877
mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561
Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis.
De Roock, W., Claes, B., Bernasconi, D., De Schutter, J., Biesmans, B., Fountzilas, G., Kalogeras, K. T., Kotoula, V., Papamichael, D., Laurent-Puig, P., et al. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70130-3 · Cited by 2,144
Self-citation
Cetuximab Plus Irinotecan, Fluorouracil, and Leucovorin As First-Line Treatment for Metastatic Colorectal Cancer: Updated Analysis of Overall Survival According to Tumor KRAS and BRAF Mutation Status
Van Cutsem, E., Köhne, C.-H., Láng, I., Folprecht, G., Nowacki, M. P., Cascinu, S., Shchepotin, I., Maurel, J., Cunningham, D., Tejpar, S., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.33.5091 · Cited by 1,882
RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
Poulikakos, P. I., Zhang, C., Bollag, G. E., Shokat, K. M., & Rosen, N. X. (2010) · Nature · doi:10.1038/nature08902 · Cited by 1,841
Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study
Douillard, J., Siena, S., Cassidy, J., Tabernero, J. M., Burkes, R. L., Barugel, M. E., Humblet, Y., Bodoky, G., Cunningham, D., Jassem, J., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.27.4860 · Cited by 1,829
Fluorouracil, Leucovorin, and Oxaliplatin With and Without Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer
Bokemeyer, C., Bondarenko, I., Makhson, A. M., Hartmann, J. T., Aparicio, J., de Braud, F., Donea, S., Ludwig, H., Schuch, G., Stroh, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.20.8397 · Cited by 1,646
Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer
Di Nicolantonio, F., Martini, M., Molinari, F., Sartore-Bianchi, A., Arena, S., Saletti, P., De Dosso, S., Mazzucchelli, L., Frattini, M., Siena, S., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.18.0786 · Cited by 1,591 · cited 1×
“Analyte extraction and mutational profiling were done as described (14, 19, 22, 23).”
Self-citation
Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF
Heidorn, S. J., Milagre, C. S., Whittaker, S. R., Nourry, A., Niculescu‐Duvaz, I., Dhomen, N. S., Hussain, J., Reis-Filho, J. S., Springer, C. J., Pritchard, C. A., et al. (2010) · Cell · doi:10.1016/j.cell.2009.12.040 · Cited by 1,497
KRAS Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab
Lièvre, A., Bachet, J., Boige, V., Cayre, A., Corre, D. L., Buc, E., Ychou, M., Bouché, O., Landi, B., Louvet, C., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2007.12.5906 · Cited by 1,485

Show all 31 references

Sorted by citations

Items 101–190 of 190

DRAP: a toolbox for drug response analysis and visualization tailored for preclinical drug testing on patient-derived xenograft models
Li, Q., Dai, W., Liu, J., Li, Y., & Li, Y. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-019-1785-7 · Cited by 23
KRAS A146 Mutations Are Associated With Distinct Clinical Behavior in Patients With Colorectal Liver Metastases
Erve, I. V. ’., Wesdorp, N. J., Medina, J. E., Ferreira, L., Leal, A., Huiskens, J., Bolhuis, K., van Waesberghe, J. T. M., Swijnenburg, R., van den Broek, D. A., et al. (2021) · JCO Precision Oncology · doi:10.1200/po.21.00223 · Cited by 23
mTOR Inhibition Elicits a Dramatic Response in PI3K-Dependent Colon Cancers
Deming, D. A., Leystra, A. A., Farhoud, M., Nettekoven, L. A., Clipson, L. J., Albrecht, D. M., Washington, M. K., Sullivan, R., Weichert, J. P., & Halberg, R. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060709 · Cited by 22
Comprehensive characterization of the patient-derived xenograft and the paralleled primary hepatocellular carcinoma cell line
Cheung, P. F., Yip, C. W., Ng, L. W. C., Lo, K. W., Chow, C., Chan, K. F., Cheung, T. T., & Cheung, S. (2016) · Cancer Cell International · doi:10.1186/s12935-016-0322-5 · Cited by 22
MEK plus PI3K/mTORC1/2 Therapeutic Efficacy Is Impacted by TP53 Mutation in Preclinical Models of Colorectal Cancer
García-García, C., Rivas, M. A., Ibrahim, Y. H., Calvo, M. T., Gris‐Oliver, A., Rodríguez, O., Grueso, J., Antón, P., Guzmán, M., Aura, C. M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3091 · Cited by 23
Self-citation
Proteomic characterization of the colorectal cancer response to chemoradiation and targeted therapies reveals potential therapeutic strategies
Li, Y., Wang, B., Ma, F., Jiang, D., Wang, Y., Li, K., Tan, S., Feng, J., Wang, Y., Qin, Z., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101311 · Cited by 23
Patient-derived models facilitate precision medicine in liver cancer by remodeling cell-matrix interaction
Chen, K., Li, Y., Wang, B., Yan, X., Tao, Y., Song, W., Xi, Z., He, K., & Xia, Q. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1101324 · Cited by 22
Lenalidomide normalizes tumor vessels in colorectal cancer improving chemotherapy activity
Leuci, V., Maione, F., Rotolo, R., Giraudo, E., Sassi, F. P., Migliardi, G., Todorovic, M., Gammaitoni, L., Mesiano, G., Giraudo, L., et al. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0872-2 · Cited by 21
Self-citation
Combination of copanlisib with cetuximab improves tumor response in cetuximab-resistant patient-derived xenografts of head and neck cancer
Klinghammer, K. F., Politz, O., Eder, T., Otto, R., Raguse, J.-D., Albers, A. E., Kaufmann, A. M., Tinhofer, I., Hoffmann, J., Keller, U. B., et al. (2020) · Oncotarget · doi:10.18632/oncotarget.27763 · Cited by 21
Treatment Individualization in Colorectal Cancer
van Geel, R. M. J. M., Beijnen, J. H., Bernards, R., & Schellens, J. H. M. (2015) · Current Colorectal Cancer Reports · doi:10.1007/s11888-015-0288-z · Cited by 20
6PPD and 6PPDQ exposure promote the proliferation and migration of non-small cell lung cancer cells through PTEN dysfunction and ARG2-mediated metabolic reprogramming
Wang, C., Lin, J., Deng, J., Li, X., Zhai, J., Yang, Y., & Luan, T. (2025) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2025.139088 · Cited by 19
The extended spectrum of RAS‐MAPK pathway mutations in colorectal cancer
Costigan, D. C., & Dong, F. (2019) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22813 · Cited by 21
Targeting the PI3K Signalling as a Therapeutic Strategy in Colorectal Cancer
Fernandes, M. S., Sanches, J., & Seruca, R. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-02771-1_4 · Cited by 18
Molecular Markers Predictive of Chemotherapy Response in Colorectal Cancer
Shiovitz, S., & Grady, W. M. (2015) · Current Gastroenterology Reports · doi:10.1007/s11894-015-0431-7 · Cited by 18
Conquering oncogenic KRAS and its bypass mechanisms
Hou, P., & Wang, Y. (2022) · Theranostics · doi:10.7150/thno.71260 · Cited by 18
The future of patient-derived xenografts in prostate cancer research
Lawrence, M. G., Taylor, R. A., Cuffe, G. B., Ang, L. S., Clark, A. K., Goode, D. L., Porter, L. H., Magnen, C. L., Navone, N. M., Schalken, J. A., et al. (2023) · Nature Reviews Urology · doi:10.1038/s41585-022-00706-x · Cited by 19
Cetuximab treatment for metastatic colorectal cancer with KRAS p.G13D mutations improves progression-free survival
Osumi, H., Shinozaki, E., Osako, M., Kawazoe, Y., Oba, M., Misaka, T., Goto, T., Kamo, H., Suenaga, M., Kumekawa, Y., et al. (2015) · Molecular and Clinical Oncology · doi:10.3892/mco.2015.602 · Cited by 17
MEK inhibitor effective against proliferation in breast cancer cell
Zhou, Y., Hu, H., Meng, W., Jiang, L., Zhang, X., Sha, J., Lu, Z., & Yang, Y. (2014) · Tumor Biology · doi:10.1007/s13277-014-1901-5 · Cited by 17
Mechanisms of KRAS inhibitor resistance in KRAS-mutant colorectal cancer harboring Her2 amplification and aberrant KRAS localization
Maruyama, K., Shimizu, Y., Nomura, Y., Oh-hara, T., Takahashi, Y., Nagayama, S., Fujita, N., & Katayama, R. (2025) · npj Precision Oncology · doi:10.1038/s41698-024-00793-6 · Cited by 16
Using Large-Scale Genomics Data to Identify Driver Mutations in Lung Cancer: Methods and Challenges
Hudson, A., Wirth, C., Stephenson, N. L., Fawdar, S., Brognard, J., & Miller, C. J. (2015) · Pharmacogenomics · doi:10.2217/pgs.15.60 · Cited by 18
p27kip1 expression and phosphorylation dictate Palbociclib sensitivity in KRAS-mutated colorectal cancer
Vinciguerra, G. L. R., Dall’Acqua, A., Segatto, I., Mattevi, M. C., Russo, F., Favero, A., Cirombella, R., Mungo, G., Viotto, D., Karimbayli, J., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-04241-2 · Cited by 16
MiR‐92a mediates AZD6244 induced apoptosis and G1‐phase arrest of lymphoma cells by targeting Bim
Lv, X., Zhang, X., Deng, L., Jiang, L., Meng, W., Lu, Z., & Wang, X. (2013) · Cell Biology International · doi:10.1002/cbin.10225 · Cited by 15
Zoledronic acid enhances the efficacy of the MEK inhibitor trametinib in KRAS mutant cancers
Dai, X., Xia, H., Zhou, S., Tang, Q., & Bi, F. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.10.022 · Cited by 15
Aspirin,PIK3CAMutation, and Colorectal-Cancer Survival
Ogino, S., Liao, X., & Chan, A. T. (2013) · New England Journal of Medicine · doi:10.1056/nejmc1214189 · Cited by 15
Co‐targeting BET , CBP , and p300 inhibits neuroendocrine signalling in androgen receptor‐null prostate cancer
Choo, N., Keerthikumar, S., Ramm, S., Ashikari, D., Teng, L., Niranjan, B., Hedwards, S., Porter, L. H., Goode, D. L., Simpson, K. J., et al. (2024) · The Journal of Pathology · doi:10.1002/path.6280 · Cited by 14
Simultaneous perturbation of the MAPK and the PI3K/mTOR pathways does not lead to increased radiosensitization
Kuger, S., Flentje, M. P., & Djuzenova, C. S. (2015) · Radiation Oncology · doi:10.1186/s13014-015-0514-5 · Cited by 16
MEK162 Enhances Antitumor Activity of 5-Fluorouracil and Trifluridine in KRAS-mutated Human Colorectal Cancer Cell Lines
Gong, J., Chen, Y., Yang, L., Pillai, R. K., Shirasawa, S., & Fakih, M. (2017) · Anticancer Research · doi:10.21873/anticanres.11634 · Cited by 14
Data augmentation and multimodal learning for predicting drug response in patient-derived xenografts from gene expressions and histology images
Partin, A., Brettin, T. S., Zhu, Y., Dolezal, J. M., Kochanny, S. E., Pearson, A. T., Shukla, M. P., Evrard, Y. A., Doroshow, J. H., & Stevens, R. L. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1058919 · Cited by 15
Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody‐“decoy” strategy
Basilico, C., Modica, C., Maione, F., Vigna, E., & Comoglio, P. M. (2018) · International Journal of Cancer · doi:10.1002/ijc.31550 · Cited by 14
Self-citation
Therapeutic Potency of PI3K Pharmacological Inhibitors of Gastrointestinal Cancer
Hashemzadeh, K., Jokar, M. H., Sedighi, S., & Moradzadeh, M. (2018) · Middle East Journal of Digestive Diseases · doi:10.15171/mejdd.2018.122 · Cited by 14
RUNX2/CBFB modulates the response to MEK inhibitors through activation of receptor tyrosine kinases in KRAS-mutant colorectal cancer
Šuštić, T., Bosdriesz, E., van Wageningen, S., Wessels, L. F. A., & Bernards, R. (2019) · Translational Oncology · doi:10.1016/j.tranon.2019.10.006 · Cited by 16
The Inositide Signaling Pathway As a Target for Treating Gastric Cancer and Colorectal Cancer
Kim, H. J., Lee, S., & Oh, S. C. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00168 · Cited by 13
Development of Preclinical Models to Understand and Treat Colorectal Cancer
Sebolt, J. S. (2018) · Clinics in Colon and Rectal Surgery · doi:10.1055/s-0037-1602240 · Cited by 12
Molecular subtypes of colorectal cancer in pre-clinical models show differential response to targeted therapies: Treatment implications beyond KRAS mutations
Pal, R., Wei, N., Song, N., Wu, S., Kim, R. S., Wang, Y., Gavin, P. G., Lucas, P. C., Srinivasan, A., Allegra, C. J., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0200836 · Cited by 12
Target Genetic Abnormalities for the Treatment of Colon Cancer and Its Progression to Metastasis
Baviskar, T., Momin, M. M., Liu, J., Guo, B., & Bhatt, L. K. (2020) · Current Drug Targets · doi:10.2174/1389450121666201119141015 · Cited by 12
Horizontal Combination of MEK and PI3K/mTOR Inhibition in BRAF Mutant Tumor Cells with or without Concomitant PI3K Pathway Mutations
Rittler, D., Molnár, E., Baranyi, M., Garay, T., Hegedüs, L., Aigner, C., Tóvári, J., Tı́már, J., & Hegedűs, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207649 · Cited by 11
Antigen Peptide Transporter 1 (TAP1) Promotes Resistance to MEK Inhibitors in Pancreatic Cancers
Li, X., Feng, Y. C., Hou, Q., Fu, Y., & Luo, Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137168 · Cited by 11
Patient-Derived Xenograft Models of Colorectal Cancer: Procedures for Engraftment and Propagation
Burgenske, D. M., Monsma, D. J., & MacKeigan, J. P. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7765-9_20 · Cited by 11
Network analysis of differential Ras isoform mutation effects on intestinal epithelial responses to TNF-α
Lau, K. S., Schrier, S. B., Gierut, J. J., Lyons, J., Lauffenburger, D. A., & Haigis, K. M. (2013) · Integrative Biology · doi:10.1039/c3ib40062j · Cited by 10
A Pilot Prospective Study of Refractory Solid Tumor Patients for NGS-Based Targeted Anticancer Therapy
Seol, Y. M., Kwon, C. H., Lee, S. J., Lee, S., Choi, Y., Choi, Y. J., Kim, H., & Park, D. Y. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.10.011 · Cited by 10
On the Analysis of Cyclic Drug Schedules for Cancer Treatment using Switched Dynamical Systems
Chapman, M. P., Mazumdar, E., Langer, E. M., Sears, R. C., & Tomlin, C. J. (2018) · IEEE Conference on Decision and Control (CDC) · doi:10.1109/cdc.2018.8619490 · Cited by 10
Modeling Drug Responses and Evolutionary Dynamics Using Patient-Derived Xenografts Reveals Precision Medicine Strategies for Triple-Negative Breast Cancer
Shea, A., Lubling, Y., Guerrero-Romero, D., García, R. M., Greenwood, W., O’Reilly, M., Georgopoulou, D., Callari, M., Lerda, G., Wix, S., et al. (2024) · Cancer Research · doi:10.1158/0008-5472.can-24-1703 · Cited by 9
A small natural molecule CADPE kills residual colorectal cancer cells by inhibiting key transcription factors and translation initiation factors
Zheng, G., Tang, M., Shu, C., Xin, W., Zhang, Y., Chi, B.-B., Shi, M., Guo, X., Zhang, Z., & Lian, X. (2020) · Cell Death and Disease · doi:10.1038/s41419-020-03191-5 · Cited by 9
Optimizing Drug Response Study Design in Patient-Derived Tumor Xenografts
Weiss, J., Pham, N., Pintilie, M., Li, M., Liu, G., Shepherd, F. A., Tsao, M., & Xu, W. (2022) · Cancer Informatics · doi:10.1177/11769351221136056 · Cited by 9
Intrinsic Epigenetic State of Primary Osteosarcoma Drives Metastasis
Singh, I., Rainusso, N. C., Kurenbekova, L., Nirala, B. K., Dou, J., Muruganandham, A., & Yustein, J. T. (2024) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-23-0055 · Cited by 9
Ex vivo treatment of patient biopsies as a novel method to assess colorectal tumour response to the MEK1/2 inhibitor, Selumetinib
Novo, S. M., Wedge, S. R., & Stark, L. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-12222-9 · Cited by 12
Multiple mechanisms involved in a low concentration of FL118 enhancement of AMR-MeOAc to induce pancreatic cancer cell apoptosis and growth inhibition.
Rabi, T., & Li, F. (2018) · Europe PMC (PubMed Central) · Cited by 9
Current understanding of comparative pathology and prospective research approaches for canine hemangiosarcoma
Suzuki, T., Henshaw, M. J., Yanagi, T., & Aoshima, K. (2023) · Research in Veterinary Science · doi:10.1016/j.rvsc.2023.105120 · Cited by 8
Role of Cellular Biomolecules in Screening, Diagnosis and Treatment of Colorectal Cancer
Mei, X.-L., & Zheng, Q.-F. (2019) · Current Drug Metabolism · doi:10.2174/1389200220666191018153428 · Cited by 7
Extracellular vesicle-mediated gene therapy targets BRAFV600E-mutant colorectal cancer by inhibiting the MEK1/2-ERK1/2 pathway
Wang, D., Wang, L., Zhang, W., Xu, K., Chen, L., Guo, Z., Wu, K., Huang, D., Zhao, Y., Yao, M., et al. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03205-4 · Cited by 7
Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines
Tabchy, A. B., Eltonsy, N. H., Housman, D. E., & Mills, G. B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060339 · Cited by 7
Patient-Derived Xenograft Models in Breast Cancer Research
Na, D., & Moon, H. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-981-32-9620-6_14 · Cited by 7
Approaches to functionally validate candidate genetic variants involved in colorectal cancer predisposition
Bonjoch, L., Mur, P., Arnau‐Collell, C., Vargas‐Parra, G., Shamloo, B., Franch‐Expósito, S., Pineda, M., Capellá, G., Erman, B., & Castellvı́-Bel, S. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2019.03.004 · Cited by 9
Distinct Transcriptional Programming Drive Response to MAPK Inhibition in BRAF V600-Mutant Melanoma Patient-Derived Xenografts
Feng, T., Golji, J., Li, A., Zhang, X., Ruddy, D. A., Rakiec, D. P., Geyer, F. C., Gu, J., Gao, H., Williams, J. A., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-19-0028 · Cited by 6
A Phase I Clinical Trial of Trametinib in Combination with TAS-102 in Patients with Chemotherapy-Resistant RAS-Mutated (PIK3CA/PTEN-Wild Type) Metastatic Colorectal Cancer
Chuang, J., Gong, J., Li, S. M., Wang, C., & Fakih, M. (2022) · Clinical Colorectal Cancer · doi:10.1016/j.clcc.2022.05.004 · Cited by 6
Anti-MEK and Anti-EGFR mAbs in RAS-Mutant Metastatic Colorectal Cancer: Case Series and Rationale
Ledys, F., Dérangère, V., Réda, M., Guion, J.-F., Milliex, R., Roux, V., Limagne, E., Arnould, L., Bengrine-Lefèvre, L., Ghiringhelli, F., et al. (2019) · Advances in Therapy · doi:10.1007/s12325-019-00949-y · Cited by 6
The role of MerTK in promoting cell migration is enhanced by the oncogenic Ras/IL‐33 signaling axis
Ohta, S., Tago, K., Kuchimaru, T., Funakoshi‐Tago, M., Horie, H., Aoki‐Ohmura, C., Matsugi, J., & Yanagisawa, K. (2021) · FEBS Journal · doi:10.1111/febs.16271 · Cited by 6
mTOR and Regulation of Translation
Tsukumo, Y., Laplante, M., Parsyan, A. E., Ruggero, D., & Fonseca, B. D. (2014) · Springer eBooks · doi:10.1007/978-94-017-9078-9_15 · Cited by 5
Phosphoinositide-3-kinase, catalytic, alpha polypeptide RNA interference inhibits growth of colon cancer cell SW948
Huang, W. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i26.3458 · Cited by 3
Patient-Derived Xenografts as Cancer Models for Preclinical Drug Screening
Williams, J. A. (2017) · Molecular and translational medicine · doi:10.1007/978-3-319-55825-7_10 · Cited by 3
Mouse Models of Kras-Mutant Colorectal Cancer: Valuable GEMMs for Drug Testing?
Nicolantonio, F. D., & Bardelli, A. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0339 · Cited by 3
Self-citation
Patient-Derived-Xenografts in Mice: A Preclinical Platform for Cancer ResearchPreprint
Cocco, E., & de Stanchina, E. (2023) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041381 · Cited by 3
Ghrelin/GHSR system attenuates collagen-induced arthritis in mice and ameliorates inflammation in human rheumatoid arthritis fibroblast-like synoviocytes
Ma, J., Zhang, J., Liu, J., Zhao, J., Wang, X., Lv, T., Lv, T., & Zhang, Y. (2025) · Biochemical Pharmacology · doi:10.1016/j.bcp.2025.116973 · Cited by 2
First-Generation Tumor Xenografts: A Link Between Patient-Derived Xenograft Models and Clinical Disease
Dong, X., Gout, P. W., Yi, L., Wang, Y., Xu, Y., & Yang, K. (2017) · Molecular and translational medicine · doi:10.1007/978-3-319-55825-7_11 · Cited by 2
Resistance of Colorectal Tumors to Anti-EGFR Antibodies
Trusolino, L., & Leto, S. M. (2018) · Resistance to targeted anti-cancer therapeutics · doi:10.1007/978-3-319-67932-7_1 · Cited by 2
Self-citation
Exploitation of Precision Medicine Trials Data: Examples of Long Responders From the SHIVA01 Trial
Basse, C., Morel, C., Callens, C., Pierron, G., Servois, V., Vincent‐Salomon, A., Jobard, A., Alt, M., Ricci, F., Loirat, D., et al. (2018) · JCO Precision Oncology · doi:10.1200/po.18.00048 · Cited by 2
Patient-Derived Tumor Xenograft
Inghirami, G., Tinkey, P. T., de Stanchina, E., & Uthamanthil, R. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804010-2.00027-8 · Cited by 2
Synthetic Genetic Approaches in Colorectal Cancer: Exploiting and Targeting Genome Instability
Sajesh, B. V., Cisyk, A. L., & McManus, K. J. (2014) · Cancer metastasis · doi:10.1007/978-3-319-12136-9_9 · Cited by 1
Genomic profiling of colorectal cancers and the future of personalized treatment
Harada, K., Kaya, D. M., Song, S., Baba, H., & Ajani, J. A. (2017) · Colorectal Cancer · doi:10.2217/crc-2016-0017 · Cited by 1
Patient-Derived Xenograft Models of Prostate Cancer
Marques, R. B., Ridder, C. M. A. D., & van Weerden, W. M. (2017) · Molecular and translational medicine · doi:10.1007/978-3-319-57424-0_8 · Cited by 1
Network Entropy Reveals that Cancer Resistance to MEK Inhibitors Is Driven by the Resilience of Proliferative Signaling
Maust, J. D., Leopold, J., & Bugrim, A. E. (2019) · Studies in computational intelligence · doi:10.1007/978-3-030-36683-4_60 · Cited by 1
Efficacy of CDK4/6 Inhibitor in Treatment of Metastatic Breast Cancer and Colon Cancer
Janet, R., Karanikolova, T., Krusteva, R., & Taushanova, M. (2020) · International Journal of Clinical Oncology and Cancer Research · doi:10.11648/j.ijcocr.20200501.11 · Cited by 1
The search for surrogacy in patient derived xenograft mouse trials: glass is less than half fullPreprint
Mistry, H. B. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.03.409730 · Cited by 1
DIFFERENTIAL PAX5 LEVELS PROMOTE MCL DISPERSAL AND PROGRESSION AND PREDICT A POOR PROGNOSIS IN ADVANCED MCL PATIENTS
Teo, A. E. (2014) · Digital Commons-TMC (Texas Medical Center)
Using GEMMs to investigate novel therapeutic strategies for colorectal cancer
Raja, M. (2013) · ORCA Online Research @Cardiff (Cardiff University)
Marqueurs moléculaires prédictifs de réponse aux thérapies ciblées dans les cancers digestifs
Perkins, G. (2012) · theses.fr (ABES) · doi:10.70675/5b4631efzc0e5z4dddz8408z43ab410793f3
Correction: Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines
Tabchy, A. B., Eltonsy, N. H., Housman, D. E., & Mills, G. B. (2013) · PLoS ONE · doi:10.1371/annotation/85d86c29-4ba6-4bf0-94f6-2977b3e1c792
Hitting cancer where it hurts most
Kuiken, H. J. (2012) · Utrecht University Repository (Utrecht University)
PDX Models of Colorectal Tumors
MacKeigan, J. P., & Burgenske, D. M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804010-2.00021-7
Deciphering mechanisms of response and resistance in large-scale mouse cancer screens
Prahallad, A., Jensen, M. R., & Chapeau, E. A. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.02.006
Inhibition of compensatory survival and proliferative pathway activation induced by mTOR inhibition in renal cell carcinoma
Bailey, S. T. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/nfxr-rg33
Cortactin Phosphorylation by Casein Kinase 2 Regulates Actin Related Protein 2/3 Complex Activity and Invadopodia Function
Markwell, S. M. (2018) · The Research Repository @ WVU (West Virginia University) · doi:10.33915/etd.3685
New Approaches for the Treatment of Triple Negative Breast Cancer
Sulaiman, A. (2019) · uO Research (University of Ottawa) · doi:10.20381/ruor-23348
Translational research of combined anticancer therapies targeting the MAPK pathway
Huijberts, S. C. F. A. (2021) · Utrecht University Repository (Utrecht University) · doi:10.33540/1019
Section I. Summary
Putney, L. G., & Gallavan, N. P. (2014) · Action in Teacher Education · doi:10.1080/01626620.2014.977693
Prädiktive Testung von Tumorgewebe und ihre klinischen Konsequenzen
Hoffmann, J. (2022) · Springer Reference Medizin · doi:10.1007/978-3-662-46764-0_148-1
Pharmacological exposure optimisation of anticancer agents during clinical development
van der Heijden, L. T. (2023) · Utrecht University Repository (Utrecht University) · doi:10.33540/2004
Patient-derived Organoids as a Tool for Advancing Precision Immuno-oncology
Than, X. Y., Ong, T. T., & Chow, E. K. (2024) · World Scientific Annual Review of Cancer Immunology · doi:10.1142/s2972389224300019
Additional file 2 of A role for the unfolded protein response stress sensor ERN1 in regulating the response to MEK inhibitors in KRAS mutant colon cancers
Šuštić, T., van Wageningen, S., Bosdriesz, E., Reid, R. J. D., Dittmar, J. C., Lieftink, C., Beijersbergen, R. L., Wessels, L. F. A., Rothstein, R. J., & Bernards, R. (2018) · Figshare · doi:10.6084/m9.figshare.7391720
DeepDrugs: a mechanism-aware tri-linear attention framework for synergistic drug-combination prediction
Xin, G., Zhu, Y., Li, Q., Han, J., Xu, Z., Wang, H., & Liu, J. (2026) · Briefings in Bioinformatics · doi:10.1093/bib/bbag205 · Cited by 1

Authors: Migliardi, G., Sassi, F., Torti, D., Galimi, F., Zanella, E. R., Buscarino, M., Ribero, D., Muratore, A., Massucco, P., Pisacane, A., Risio, M., Capussotti, L., Marsoni, S., Di Nicolantonio, F., Bardelli, A., Comoglio, P. M., Trusolino, L., & Bertotti, A.
Affiliations: Candiolo Cancer Institute (IT)
Authors' Affiliations: 1Laboratory of Molecular Pharmacology, 2Laboratory of Molecular Genetics, 3Division of Surgical Oncology, 4Unit of Pathology, 5Clinical Coordination Unit, 6Molecular Clinical Oncology, Institute for Cancer Research and Treatment (IRCC); 7Department of Oncological Sciences, University of Torino Medical School, Candiolo; 8Department of Surgery, Mauriziano Umberto I Hospital, Torino; 9Southern Europe New Drug Organization (SENDO) Foundation; and 10FIRC Institute of Molecular Oncology (IFOM), Milano, Italy
ORCID: Migliardi, Giorgia
Sassi, Francesco
Galimi, Francesco
Zanella, Eugenia R.
Ribero, Dario
Muratore, Andrea
Massucco, Paolo
Marsoni, Silvia
Bardelli, Alberto
Comoglio, Paolo M.
Trusolino, Livio
Bertotti, Andrea
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2012-04-30
Volume: 18
Issue: 9
Pages: 2515-2525
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-11-2683
OpenAlex: W2096218887
Semantic Scholar: e3d0b63472624f0def1ca1f4023cc3c8049077f4
Cited by: 191
References: 31
Citations by year: 2026: 1 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 15 · 2019: 20 · 2018: 23 · 2017: 15 · 2016: 15 · 2015: 22 · 2014: 21 · 2013: 17 · 2012: 6
FWCI: 10.37
Type: journal article
Language: en
Open access: green
hdl.handle.net
Licence: other-oa
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
Funders: Regione Piemonte
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords: metastatic colorectal cancer, MEK inhibition, PI3K/mTOR inhibition, selumetinib, BEZ235, cetuximab, combination therapy, patient-derived xenografts, KRAS mutation, NRAS mutation, BRAF mutation, PIK3CA mutation, PI3K/Akt signaling, tumor growth inhibition, tumor regression, anti-EGFR therapy resistance, NOD/SCID mice
MeSH terms: Aged, Aged, 80 and over, Animals, Colon, Female, Humans, Immunoenzyme Techniques, Liver Neoplasms, Male, Middle Aged, Mutation, Genes, ras, Rectum, Colorectal Neoplasms, Case-Control Studies, Mice, SCID, Mice, Inbred NOD, 1-Phosphatidylinositol 4-Kinase, Mitogen-Activated Protein Kinase Kinases, Xenograft Model Antitumor Assays, Cell Line, Tumor, Protein Kinase Inhibitors, Extracellular Signal-Regulated MAP Kinases, Proto-Oncogene Proteins B-raf, Mice, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Inhibition of MEK and PI3K/mTOR Suppresses Tumor Growth but Does Not Cause Tumor Regression in Patient-Derived Xenografts of RAS-Mutant Colorectal Carcinomas

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks