The mTORC1 Inhibitor Everolimus Prevents and Treats Eμ- Myc Lymphoma by Restoring Oncogene-Induced Senescence
Open accessPublished version of a preprint
Abstract
MYC deregulation is common in human cancer. IG-MYC translocations that are modeled in Eμ-Myc mice occur in almost all cases of Burkitt lymphoma as well as in other B-cell lymphoproliferative disorders. Deregulated expression of MYC results in increased mTOR complex 1 (mTORC1) signaling. As tumors with mTORC1 activation are sensitive to mTORC1 inhibition, we used everolimus, a potent and specific mTORC1 inhibitor, to test the requirement for mTORC1 in the initiation and maintenance of Eμ-Myc lymphoma. Everolimus selectively cleared premalignant B cells from the bone marrow and spleen, restored a normal pattern of B-cell differentiation, and strongly protected against lymphoma development. Established Eμ-Myc lymphoma also regressed after everolimus therapy. Therapeutic response correlated with a cellular senescence phenotype and induction of p53 activity. Therefore, mTORC1-dependent evasion of senescence is critical for cellular transformation and tumor maintenance by MYC in B lymphocytes. Significance: This work provides novel insights into the requirements for MYC-induced oncogenesis by showing that mTORC1 activity is necessary to bypass senescence during transformation of B lymphocytes. Furthermore, tumor eradication through senescence elicited by targeted inhibition of mTORC1 identifies a previously uncharacterized mechanism responsible for significant anticancer activity of rapamycin analogues and serves as proof-of-concept that senescence can be harnessed for therapeutic benefit. Cancer Discov; 3(1); 82–95. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 1
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
Cites
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?
mTOR inhibitors (rapalogs) might induce or prevent senescence in a context-dependent manner.
“These findings suggest that mTOR inhibitors, commonly referred to as rapalogs, might induce or prevent senescence in a context- dependent manner 45,48,49 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [48]
The Results section ('Everolimus induces cellular senescence'; page unavailable) reports senescence after treatment with the mTORC1 inhibitor everolimus, and the Discussion says rapamycin rescued RAS-induced senescence. The paper does not report rapalogs preventing senescence in another context: it distinguishes inhibition of senescence by PI3K/AKT/mTOR signaling from inhibition of that signaling by a drug. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn Eμ-Myc mice, the mTOR inhibitor everolimus causes lymphoma regression.
“| mTOR inhibitor | Eμ-Myc | | | | Everolimus | Lymphoma regression | 160 |”
From Inside and out: the activities of senescence in cancer (2014) · cites this paper as [160]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., Grünwald, V., Thompson, J. A., Figlin, R. A., Hollaender, N., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61039-9 · Cited by 3,019 · see citing works
p53-dependent apoptosis modulates the cytotoxicity of anticancer agents
Lowe, S. W., Ruley, H. E., Jacks, T., & Housman, D. E. (1993) · Cell · doi:10.1016/0092-8674(93)90719-7 · Cited by 2,911 · see citing works
Self-citationThe selectivity of protein kinase inhibitors: a further update
Bain, J., Plater, L., Elliott, M., Shpiro, N., Hastie, C. J., McLauchlan, H., Klevernic, I. V., Arthur, J. S. C., Alessi, D. R., & Cohen, P. (2007) · Biochemical Journal · doi:10.1042/bj20070797 · Cited by 2,522 · see citing works
Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas
Xue, W., Zender, L., Miething, C., Dickins, R. A., Hernando, E., Krizhanovsky, V., Cordon-Cardo, C., & Lowe, S. W. (2007) · Nature · doi:10.1038/nature05529 · Cited by 2,473 · see citing works
Self-citationRb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence
Narita, M., Nuñez, S., Heard, E., Narita, M., Lin, A. W., Hearn, S. A., Spector, D. L., Hannon, G. J., & Lowe, S. W. (2003) · Cell · doi:10.1016/s0092-8674(03)00401-x · Cited by 2,278 · see citing works
Self-citationThe c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice
Adams, J. M., Harris, A. W., Pinkert, C. A., Corcoran, L. M., Alexander, W. S., Cory, S., Palmiter, R. D., & Brinster, R. L. (1985) · Nature · doi:10.1038/318533a0 · Cited by 1,778 · see citing works
Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow.
Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D., & Hayakawa, K. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.5.1213 · Cited by 1,604 · see citing works
Regulation of the mTOR Complex 1 Pathway by Nutrients, Growth Factors, and Stress
Sengupta, S., Peterson, T. R., & Sabatini, D. M. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.026 · Cited by 1,234 · see citing works
MYC oncogenes and human neoplastic disease
Nesbit, C. E., Tersak, J. M., & Prochownik, E. V. (1999) · Oncogene · doi:10.1038/sj.onc.1202746 · Cited by 1,163 · see citing works
Freund, A., Patil, C. K., & Campisi, J. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.69 · Cited by 1,039 · see citing works
Everolimus for Subependymal Giant-Cell Astrocytomas in Tuberous Sclerosis
Krueger, D. A., Caré, M. M., Holland, K. D., Agricola, K. D., Tudor, C., Mangeshkar, P., Wilson, K. A., Byars, A. W., Sahmoud, T., & Franz, D. N. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1001671 · Cited by 1,003 · see citing works
Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., et al. (2004) · Nature Medicine · doi:10.1038/nm1052 · Cited by 964 · see citing works
MYC as a regulator of ribosome biogenesis and protein synthesis
van Riggelen, J., Yetil, A., & Felsher, D. W. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2819 · Cited by 956 · see citing works
Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy
Wendel, H., de Stanchina, E., Fridman, J. S., Malina, A., Ray, S., Kogan, S. C., Cordon‐Cardo, C., Pelletier, J., & Lowe, S. W. (2004) · Nature · doi:10.1038/nature02369 · Cited by 956 · see citing works
Self-citationMYC-Induced Cancer Cell Energy Metabolism and Therapeutic Opportunities
Dang, C. V., Le, A., & Gao, P. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-0889 · Cited by 934 · see citing works
Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2
Strasser, A., Harris, A. W., Bath, M. L., & Cory, S. (1990) · Nature · doi:10.1038/348331a0 · Cited by 905 · see citing works
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J., & Cleveland, J. L. (1999) · Genes & Development · doi:10.1101/gad.13.20.2658 · Cited by 819 · see citing works
Bywater, M. J., Poortinga, G., Sanij, E., Hein, N., Peck, A., Cullinane, C. M., Wall, M., Cluse, L. A., Drygin, D., Anderes, K. L., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.019 · Cited by 561 · see citing works
Self-citationThe Myc oncoprotein as a therapeutic target for human cancer
Vita, M. F., & Arsenian‐Henriksson, M. (2006) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2006.07.015 · Cited by 554 · see citing works
A negative feedback signaling network underlies oncogene-induced senescence
Courtois-Cox, S., Genther Williams, S. M., Reczek, E. E., Johnson, B. W., McGillicuddy, L. T., Johannessen, C. M., Hollstein, P. E., MacCollin, M., & Cichowski, K. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.10.003 · Cited by 501 · see citing works
Beuvink, I., Boulay, A., Fumagalli, S., Zilbermann, F., Ruetz, S., O’Reilly, T., Natt, F., Hall, J., Lane, H. A., & Thomas, G. (2005) · Cell · doi:10.1016/j.cell.2004.12.040 · Cited by 484 · see citing works
Bim is a suppressor of Myc-induced mouse B cell leukemia
Egle, A., Harris, A. W., Bouillet, P., & Cory, S. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401471101 · Cited by 482 · see citing works
Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants
Hemann, M. T., Bric, A., Teruya‐Feldstein, J., Herbst, A., Nilsson, J. A., Cordon‐Cardo, C., Cleveland, J. L., Tansey, W. P., & Lowe, S. W. (2005) · Nature · doi:10.1038/nature03845 · Cited by 452 · see citing works
Self-citationSuppression of Myc oncogenic activity by ribosomal protein haploinsufficiency
Barna, M., Pusic, A., Zollo, O., Costa, M. J., Kondrashov, N., Rego, E., Rao, P., & Ruggero, D. (2008) · Nature · doi:10.1038/nature07449 · Cited by 434 · see citing works
The c-myc oncogene perturbs B lymphocyte development in Eμ-myc transgenic mice
Langdon, W. Y., Harris, A. W., Cory, S., & Adams, J. M. (1986) · Cell · doi:10.1016/0092-8674(86)90361-2 · Cited by 433 · see citing works
Harris, A. W., Pinkert, C. A., Crawford, M., Langdon, W. Y., Brinster, R. L., & Adams, J. M. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.167.2.353 · Cited by 432 · see citing works
c-Myc enhances protein synthesis and cell size during B lymphocyte development
Iritani, B. M., & Eisenman, R. N. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13180 · Cited by 364 · see citing works
Gera, J., Mellinghoff, I., Shi, Y.-J., Rettig, M., Tran, C., Hsu, J.-H., Sawyers, C., & Lichtenstein, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309999200 · Cited by 345 · see citing works
Rakhra, K., Bachireddy, P., Zabuawala, T., Zeiser, R., Xu, L., Kopelman, A., Fan, A. C., Yang, Q., Braunstein, L., Crosby, E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.002 · Cited by 339 · see citing works
Mondesire, W. H., Jian, W., Zhang, H., Ensor, J., Hung, M., Mills, G. B., & Meric‐Bernstam, F. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0361 · Cited by 319 · see citing works
mTORC1 promotes survival through translational control of Mcl-1
Mills, J. R., Hippo, Y., Robert, F., Chen, S. M. H., Malina, A., Lin, C.-J., Trojahn, U., Wendel, H.-G., Charest, A., Bronson, R. T., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804821105 · Cited by 285 · see citing works
Self-citationKomarova, E. A., Chernov, M. V., Franks, R., Wang, K., Armin, G., Zelnick, C. R., Chin, D. M., Bacus, S. S., Stark, G. R., & Gudkov, A. V. (1997) · The EMBO Journal · doi:10.1093/emboj/16.6.1391 · Cited by 272 · see citing works
Abrogation of BRAFV600E-induced senescence by PI3K pathway activation contributes to melanomagenesisPreprint
Vredeveld, L. C. W., Possik, P. A., Smit, M. A., Meissl, K., Michaloglou, C., Horlings, H. M., Ajouaou, A., Kortman, P. C., Dankort, D. L., McMahon, M., et al. (2012) · Genes & Development · doi:10.1101/gad.187252.112 · Cited by 258 · see citing works
Rapamycin Extends Maximal Lifespan in Cancer-Prone Mice
Anisimov, V. N., Zabezhinski, M. A., Popovich, I. G., Piskunova, T. S., Semenchenko, A. V., Тындык, М. Л., Yurova, M. N., Antoch, M. P., & Blagosklonny, M. V. (2010) · American Journal Of Pathology · doi:10.2353/ajpath.2010.091050 · Cited by 254 · see citing works
Cdk2 suppresses cellular senescence induced by the c-myc oncogene
Campaner, S., Doni, M., Hydbring, P., Verrecchia, A., Bianchi, L., Sardella, D., Schleker, T., Perna, D., Tronnersjö, S., Murga, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb2004 · Cited by 251 · see citing works
Mabuchi, S., Altomare, D. A., Cheung, M., Zhang, L., Poulikakos, P. I., Hensley, H. H., Schilder, R. J., Ozols, R. F., & Testa, J. R. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2770 · Cited by 233 · see citing works
Kennedy, A. L., Morton, J. P., Manoharan, I., Nelson, D. M., Jamieson, N. B., Pawlikowski, J. S., McBryan, T., Doyle, B., McKay, C., Oien, K. A., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.02.020 · Cited by 213 · see citing works
Lindemann, R. K., Newbold, A., Whitecross, K. F., Cluse, L. A., Frew, A. J., Ellis, L., Williams, S. P., Wiegmans, A. P., Dear, A. E., Scott, C. L., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702294104 · Cited by 199 · see citing works
Self-citationTumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184 · see citing works
Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies
Xu-Monette, Z. Y., Medeiros, L. J., Li, Y., Orlowski, R. Z., Andreeff, M., Bueso-Ramos, C., Greiner, T. C., McDonnell, T. J., & Young, K. H. (2012) · Blood · doi:10.1182/blood-2011-11-366062 · Cited by 181 · see citing works
RAD001 (Everolimus) Delays Tumor Onset and Progression in a Transgenic Mouse Model of Ovarian Cancer
Mabuchi, S., Altomare, D. A., Connolly, D. C., Klein–Szanto, A. J., Litwin, S., Hoelzle, M. K., Hensley, H. H., Hamilton, T. C., & Testa, J. R. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4490 · Cited by 181 · see citing works
Crazzolara, R., Cisterne, A., Thien, M., Hewson, J. W., Baraz, R., Bradstock, K. F., & Bendall, L. J. (2009) · Blood · doi:10.1182/blood-2008-02-137752 · Cited by 121 · see citing works
Yan, H., Frost, P., Shi, Y., Hoang, B. Q., Sharma, S., Fisher, M., Gera, J., & Lichtenstein, A. K. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2447 · Cited by 108 · see citing works
van Riggelen, J., Müller, J., Otto, T., Beuger, V., Yetil, A., Choi, P. S., Kosan, C., Möröy, T., Felsher, D. W., & Eilers, M. (2010) · Genes & Development · doi:10.1101/gad.585710 · Cited by 105 · see citing works
Translational control of c-MYC by rapamycin promotes terminal myeloid differentiation.
Wall, M., Poortinga, G., Hannan, K., Pearson, R., Hannan, R., & McArthur, G. (2008) · Blood · doi:10.1182/blood-2007-09-111856 · Cited by 103 · see citing works
Self-citationXing, D., & Oršulić, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502256102 · Cited by 98 · see citing works
Determinants of Sensitivity and Resistance to Rapamycin-Chemotherapy Drug Combinations In vivo
Wendel, H., Malina, A., Zhao, Z., Zender, L., Kogan, S. C., Cordon‐Cardo, C., Pelletier, J., & Lowe, S. W. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0419 · Cited by 96 · see citing works
Self-citationRaimondi, A. R., Molinolo, A., & Gutkind, J. S. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-4645 · Cited by 88 · see citing works
Seager, C. M., Puzio‐Kuter, A. M., Patel, T., Jain, S., Cordon‐Cardo, C., Kiernan, J. M., & Abate-Shen, C. T. (2009) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-09-0169 · Cited by 84 · see citing works
Namba, R., Young, L. J. T., Abbey, C. K., Kim, L., Damonte, P., Borowsky, A. D., Qi, J., Tepper, C. G., MacLeod, C. L., Cardiff, R. D., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-2170 · Cited by 81 · see citing works
Ravitz, M. J., Chen, L., Lynch, M. C., & Schmidt, E. V. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-4351 · Cited by 54 · see citing works
Wiegmans, A. P., Alsop, A. E., Bots, M. L., Cluse, L. A., Williams, S. P., Banks, K.-M., Ralli, R., Scott, C. L., Frenzel, A., Villunger, A., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3289 · Cited by 53 · see citing works
Self-citationJacobsen, K. A., Prasad, V., Sidman, C., & Osmond, D. G. (1994) · Blood · doi:10.1182/blood.v84.8.2784.2784 · Cited by 49 · see citing works
Smardova (2010) · International Journal of Oncology · doi:10.3892/ijo_00000545 · Cited by 46 · see citing works
Robledo, C., Garcı́a, J. L., Caballero, D., et al. (2009) · Cancer · doi:10.1002/cncr.24430 · Cited by 33 · see citing works
Multiple mechanisms of tumorigenesis in E mu-myc transgenic mice.
Sidman, C. L., Denial, T. M., Marshall, J. D., et al. (1993) · PubMed · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [34]Kuilman T Michaloglou C Mooi WJ Peeper DS The essence of senescence Genes Dev 2010 24 2463 79 21078816 PMC2975923
Cited by
Sorted by citations
Unmasking senescence: context-dependent effects of SASP in cancer
Faget, D. V., Ren, Q., & Stewart, S. A. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0156-2 · Cited by 863 · see citing works
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794 · see citing works
Inside and out: the activities of senescence in cancer
Pérez-Mancera, P. A., Young, A. R. J., & Narita, M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3773 · Cited by 462 · see citing works
Elkabets, M., Vora, S., Juric, D., Morse, N., Mino-Kenudson, M., Muranen, T., Tao, J., Campos, A. B., Rodon, J., Ibrahim, Y. H., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005747 · Cited by 332 · see citing works
Georgilis, A., Klotz, S., Hanley, C. J., Herranz, N., Weirich, B., Morancho, B., Leote, A. C., D'Artista, L., Gallage, S., Seehawer, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.007 · Cited by 237 · see citing works
“Preliminary evidence indicates that uncoupling cell arrest and the SASP is feasible (Herranz et al., 2015; Laberge et al., 2015; Tasdemir et al., 2016; Wall et al., 2013).”
BackgroundOncogene-induced senescence: From biology to therapy
Zhu, H., Blake, S., Kusuma, F. K., Pearson, R. B., Kang, J., & Chan, K. T. (2020) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2020.111229 · Cited by 116 · see citing works
Self-citation
- Authors
- Wall, M., Poortinga, G., Stanley, K. L., Lindemann, R. K., Bots, M., Chan, C. J., Bywater, M. J., Kinross, K. M., Astle, M. V., Waldeck, K., Hannan, K. M., Shortt, J., Smyth, M. J., Lowe, S. W., Hannan, R. D., Pearson, R. B., Johnstone, R. W., & McArthur, G. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Merck KGaA, Darmstadt (Germany) (DE)
- ORCID
- Venue
- Cancer Discovery
- Published
- 2013-01-01
- Volume
- 3
- Issue
- 1
- Pages
- 82-95
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- PMC
- PMC3547521
- OpenAlex
- W2084839831
- Cited by
- 64
- References
- 57
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 6 · 2018: 7 · 2017: 2 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 8
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Cancer Discovery (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (P01CA087497, P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- everolimus, mTORC1 inhibition, Eμ-Myc lymphoma, MYC deregulation, oncogene-induced senescence, senescence evasion, B-cell lymphoma, Burkitt lymphoma, p53 activation, rapamycin analogs, tumor regression
- MeSH terms
- Everolimus, Mechanistic Target of Rapamycin Complex 1, Animals, Antineoplastic Agents, B-Lymphocytes, Cell Differentiation, Lymphoma, Male, Mice, Transgenic, Proteins, Proto-Oncogene Proteins c-myc, Cellular Senescence, Sirolimus, Multiprotein Complexes, 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
