The cell-line-derived subcutaneous tumor model in preclinical cancer research

Stephen M. Stribbling, Anderson J. Ryan

Published: 2022-07-19 DOI: 10.1038/s41596-022-00709-3

subcutaneous tumor model

preclinical cancer research

tumor-bearing animals

drug development

cell-line-derived tumors

AI 解读

Genetic manipulation and immortalized culture of ex vivo primary human germinal center B cells

The cell-line-derived subcutaneous tumor model in preclinical cancer research

Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses

NovoSpaRc: flexible spatial reconstruction of single-cell gene expression with optimal transport

Genome-wide pooled CRISPR screening in neurospheres

High-throughput cultivation and identification of bacteria from the plant root microbiota

Viral crosslinking and solid-phase purification enables discovery of ribonucleoprotein complexes on incoming RNA virus genomes

Mitochondrial single-cell ATAC-seq for high-throughput multi-omic detection of mitochondrial genotypes and chromatin accessibility

Addendum: Micro-CT acquisition and image processing to track and characterize pulmonary nodules in mice

Multiplexed single-cell proteomics using SCoPE2

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Tumor-bearing experimental animals are essential for preclinical cancer drug development. A broad range of tumor models is available, with the simplest and most widely used involving a tumor of mouse or human origin growing beneath the skin of a mouse: th
Introduction
Materials
Procedure
Troubleshooting
Timing
Anticipated results
References
ACKNOWLEDGMENTS

Ireson, C. R., Alavijeh, M. S., Palmer, A. M., Fowler, E. R. & Jones, H. J. The role of mouse tumour models in the discovery and development of anticancer drugs. Br. J. Cancer 121, 101–108 (2019).
Herter-Sprie, G. S., Kung, A. L. & Wang, K.-K. New cast for a new era: preclinical cancer drug development revisited. J. Clin. Invest. 123, 3639–3645 (2013).
Damia, G. & D´Incalci, M. Contemporary pre-clinical development of anticancer agents—what are the optimal preclinical models? Eur. J. Cancer 45, 2768–2781 (2009).
Ahmad, A. S., Ormiston-Smith, N. & Sasieni, P. D. Trends in the lifetime risk of developing cancer in Great Britain: comparison of risk for those born from 1930 to 1960. Br. J. Cancer 112, 943–947 (2015).
Morton, C. L. & Houghton, P. J. Establishment of human tumor xenografts in immunodeficient mice. Nat. Protoc. 2, 247–250 (2007).
Gengenbacher, N., Singhal, M. & Augustin, H. G. Preclinical mouse solid tumour models: status quo, challenges and perspectives. Nat. Rev. Cancer 17, 751–765 (2017).
Teicher, B. A. Tumor models for efficacy determination. Mol. Cancer Ther. 5, 2435–2443 (2006).
Carver, B. S. & Pandolfi, P. P. Mouse modelling in oncologic preclinical and translational research. Clin. Cancer Res. 12, 5305–5311 (2006).
Junttila, M. R. & de Sauvage, F. J. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501, 346–354 (2013).
Sikder, H. et al. Disruption of ID1 reveals major differences in angiogenesis between transplanted and autochthonous tumours. Cancer Cell 4, 291–299 (2003).
Frese, K. K. & Tuveson, D. A. Maximizing mouse cancer models. Nat. Rev. Cancer 7, 654–658 (2007).
Klein, C. A. Parallel progression of parallel tumours and metastases. Nat. Rev. Cancer 9, 302–312 (2009).
Sharpless, N. E. & DePinho, R. A. The mighty mouse: genetically engineered mouse models in cancer drug development. Nat. Rev. Drug Discov. 5, 741–754 (2006).
Fidler, I. J. & Kripke, M. L. The challenge of targeting metastasis. Cancer Metastasis Rev. 34, 635–641 (2015).
Spano, D., Heck, C., De Antonellis, P., Christofori, G. & Zollo, M. Molecular networks that regulate cancer metastasis. Semin. Cancer Biol. 22, 234–249 (2012).
Bugge, T. H. et al. Growth and dissemination of Lewis lung carcinoma in plasminogen-deficient mice. Blood 90, 4522–4531 (1997).
Rose, D. P., Connolly, J. M. & Liu, X. H. Effects of linoleic acid on the growth and metastasis of two human breast cancer cell lines in nude mice and the invasive capacity of these cell lines in vitro. Cancer Res. 54, 6557–6562 (1994).
Bailey-Downs, L. C. et al. Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression. PLoS One 9, e98624 (2014).
Hidalgo, M. et al. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discov. 4, 998–1013 (2014).
Tentler, J. J. et al. Patient-derived tumour xenografts as models for oncology drug development. Nat. Rev. Clin. Oncol. 9, 338–350 (2012).
DeRose, Y. S. et al. Tumor grafts derived from women with breast cancer authentically reflect tumor pathology, growth, metastasis and disease outcomes. Nat. Med. 17, 1514–1520 (2011).
Siolas, D. & Hannon, G. J. Patient-derived tumour xenografts: transforming clinical samples into mouse models. Cancer Res. 73, 5315–5319 (2013).
Julien, S. et al. Characterisation of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin. Cancer Res. 18, 5314–5328 (2012).
Clohessy, J. G. & Pandolfi, P. P. Mouse hospital and co-clinical trial project—from bench to bedside. Nat. Rev. Clin. Oncol. 12, 491–498 (2015).
Zitvogel, L., Pitt, J. M., Daillè, R., Smythe, M. J. & Kroemer, G. Mouse models in oncoimmunology. Nat. Rev. Cancer 16, 759–773 (2016).
Simpson-Abelson, M. R. et al. Long-term engraftment and expansion of tumor-derived memory T cells following the implantation of non-disrupted pieces of human lung tumor into NOD-scid IL2Rγnull mice. J. Immunol. 180, 7009–7018 (2008).
Lang, J., Weiss, N., Freed, B. M., Torres, R. & Pelonda, R. Generation of hematopoetic humanized mice in the newborn BALB/c-Rag2null IL2rγnull mouse model: a multivariable optimization approach. Clin. Immunol. 140, 102–116 (2011).
Lawrence, M. G. et al. Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer. Prostate 75, 1475–1483 (2015).
Couzin-Frankel, J. The littlest patient. Science 346, 24–27 (2014).
Delitto, D. et al. Patient-derived xenograft models for pancreatic adenocarcinoma demonstrate retention of tumor morphology through incorporation of murine stromal elements. Am. J. Pathol. 185, 1297–1303 (2015).
Eirew, P. et al. Dynamics of genomic clones in breast cancer patient xenografts at single cell resolution. Nature 518, 422–426 (2015).
Baklaushev, V. P. et al. Luciferase expression allows bioluminescence imaging but imposes limitations on the orthotopic mouse (4T1) model of breast cancer. Sci. Rep. 17, 1–17 (2017).
Day, C. P. et al. “Glowing head” mice: a genetic tool enabling reliable preclinical image-based evaluation of cancers in immunocompetent allografts. PLoS One 9, e109956 (2014).
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 647–674 (2011).
Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).
Willoughby, C.E. et al. Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy. J. Clin. Invest. 130, 258–271 (2020).
Jiang, Y., Willmore, E., Wedge, S.R. & Ryan, A.J. DNAPK inhibition preferentially compromises the repair of radiation-induced DNA double-strand breaks in chronically hypoxic tumor cells in xenograft models. Mol. Cancer Ther. 20, 1663–1671 (2021).
Byrne, A. T. et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat. Rev. Cancer 17, 254–268 (2017).
Inoue, T., Terada, N., Kobayashi, T. & Ogawa, O. Patient-derived xenografts as in vivo models for research in urological malignancies. Nat. Rev. Urol. 14, 267–283 (2017).
Olson, B., Li, Y., Lin, Y., Liu, E. T. & Patnai, A. Mouse models for cancer immunotherapy research. Cancer Discov. 8, 1358–1365 (2018).
Prochazka, M., Gaskins, H. R., Shiltz, L. D. & Leiter, E. H. The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. Proc. Natl. Acad. Sci. USA. 89, 3290–3294 (1992).
Floersheim, G. L., Nassenstein, D. & Torhorst, J. Growth of human tumours in mice after short-term immunosuppression with procarbazine, cyclophosphamide and antilymphocyte serum. Transplantation 30, 275–280 (1980).
Floersheim, G. L. Comparative growth of human tumors in pharmacologically immunosuppressed, immune-deprived, cyclosporin A-treated and nude mice. Eur. J. Cancer Clin. Oncol. 18, 589–594 (1982).
Jivrajani, M., Shaikh, M. V., Shrivastava, N. & Nivsarkar, M. An improved and versatile immunosuppression protocol for the development of tumor xenograft in mice. Anticancer Res. 34, 7177–7183 (2014).
Diehl, R. et al. Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches. Cell Mol. Immunol. 14, 146–179 (2017).
Sominski, D. D. et al. Development of a squamous cell carcinoma mouse model for immunotoxicity testing. J. Immunotox. 13, 226–234 (2016).
Bugelski, P. J. et al. Critical review of preclinical approaches to evaluate the potential of immunosuppressive drugs to influence human neoplasia. Int. J. Toxicol. 29, 435–466 (2010).
Miller, L. R. et al. Considering sex as a biological variable in preclinical research. FASEB J. 31, 29–34 (2017).
Bailoo, J. D., Reichlin, T. S. & Wurbel, H. Refinement of experimental design and conduct in laboratory research. ILAR J. 55, 383–391 (2014).
Clayton, J. A. Studying both sexes: a guiding principle for biomedicine. FASEB J. 30, 519–524 (2016).
Reed, M. J. et al. The effects of aging on tumor growth and angiogenesis are tumor-cell dependent. Int. J. Cancer 120, 753–760 (2006).
Ershler, W. B., Gamelli, R. L., Moore, A. L., Hacker, M. P. & Blow, A. J. Experimental tumors and aging: local factors that may account for the observed age advantage in the B16 murine melanoma model. Exp. Gerontol. 19, 367–376 (1984).
Tsuda, T. et al. Role of the thymus and T-cells in slow growth of B16 melanoma in old mice. Cancer Res. 47, 3097–3100 (1987).
Balducci, L. & Ershler, W. B. Cancer and ageing: a nexus at several levels. Nat. Rev. Cancer 5, 655–662 (2005).
Currer, J. M., Witham, B., Linder, C. and Flurkey, K. in The Jackson Laboratory Handbook on Genetically Standardized Mice Edn. 6 (eds. Flurkey, K., Currer, J. M., Leiter, E. H. & Witham, B.) 149–164 (The Jackson Laboratory, 2009).
Dell, R. B., Holleran, S. & Ramakrishnan, R. Sample size determination. ILAR J. 43, 207–213 (2002).
Prasad, V. V. T. S. & Gopalan, R. O. G. Continued use of MDA-MB-435, a melanoma cell line, as a model for human breast cancer, even in year, 2014. NPJ Breast Cancer 1, 15002 (2015).
Holliday, D. L. & Speirs, V. Choosing the right cell line for breast cancer research. Breast Cancer Res. 13, 215–222 (2011).
Culture of Animal Cells: A Manual of Basic Techniques and Specialized Applications Edn. 7 (ed. Freshney, R. I.) (John Wiley & Sons, Hoboken, New Jersey, USA, 2010).
Nikfarjam, L. & Farzaneh, P. Prevention and detection of mycoplasma contamination in cell culture. Cell J. 13, 203–212 (2012).
Zhang, X. et al. A renewable tissue resource of phenotypically stable, biologically and ethnically diverse, patient-derived human breast cancer xenograft models. Cancer Res. 73, 4885–4897 (2013).
Dall, G., Vieusseux, J., Unsworth, A., Anderson, R. & Britt, K. Low dose, low cost estradiol pellets can support MCF-7 tumour growth in nude mice without bladder symptoms. J. Cancer 6, 1331–1336 (2015).
Ström, J. O., Theodorsson, A., Ingberg, E., Isaksson, I. M. & Theodorsson, E. Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration. J. Vis. Exp. 2012, e4013 (2012).
Ingberg, E., Theodorsson, A., Theodorsson, E. & Ström, J. O. Methods for long-term17ß-estradiol administration to mice. Gen. Comp. Endocrinol. 175, 188–193 (2012).
Fridman, R. et al. Enhanced tumor growth of both primary and established human and murine tumor cells in athymic mice after coinjection with Matrigel. J. Natl Cancer Inst. 83, 769––774 (1991).
Mehta, R. R., Graves, J. M., Hart, G. D., Shilkaitis, A. & DasGupta, T. K. Growth and metastasis of human breast carcinomas with Matrigel in athymic mice. Breast Cancer Res. Treat. 25, 65–71 (1993).
Mullen, P., Ritchie, A., Langdon, S. P. & Miller, W. R. Effect of Matrigel on the tumorigenicity of human breast and ovarian carcinoma cell lines. Int. J. Cancer 67, 816–820 (1996).
Tomayko, M. M. & Reynolds, C. P. Determination of subcutaneous tumour size in athymic (nude) mice. Cancer Chemother. Pharmacol. 24, 148–154 (1989).
Workman, P. et al. Guidelines for the welfare and use of animals in cancer research. Br. J. Cancer 102, 1555–1577 (2010).
Shah, S. M., Jain, A. S., Kaushik, R., Nagarsenker, M. S. & Nerurkar, M. J. Preclinical formulations: insight, strategies, and practical considerations. AAPS PharmSciTech 15, 1307–1323 (2014).
Hedrich, H. J. (ed.) The Laboratory Mouse Edn. 2 (Academic, 2012).
Benzonana, L. L. et al. Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia inducible factor cellular signalling pathway in vitro. Anesthesiology 119, 593–605 (2013).
Huitink, J. M. et al. Volatile anesthetics modulate gene expression in breast and brain tumor cells. Anesth. Analg. 111, 1411–1415 (2010).
Wigmore, T. J., Mohammed, K. & Jhanji, S. Long-term survival for patients undergoing volatile versus IV anesthesia for cancer surgery: a retrospective analysis. Anesthesiology 124, 69–79 (2016).
Tiouririne, M. et al. IV Lidocaine for Patients Undergoing Primary Breast Cancer Surgery: Effects on Postoperative Recovery and Cancer Recurrence. ClinicalTrials.gov Identifier: NCT01204242 (2022).
Wall, T. et al. Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review. Br. J. Anaesth. 123, 135–150 (2019).
Bhat, S. A. et al. Long non-coding RNAs: mechanism of action and functional utility. Noncoding RNA Res. 1, 43–50 (2016).
Kilkenny, C., Browne, W. J., Cuthill, I. C., Emerson, M. & Altman, D. G. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 8, e1000412 (2010).
Sugar, E., Pascoe, A. J. & Azad, N. Reporting of preclinical tumor-graft cancer therapeutic studies. Cancer Biol. Ther. 13, 1262–1268 (2012).
MacCallum, C. J. Reporting animal studies: good science and a duty of care. PLoS Biol. 8, e1000413 (2010).
Drobnitzky, N. Novel Therapeutic Strategies for Targeting EGFR Mutated Non-Small Cell Lung cancer. PhD thesis, Univ. Oxford (2017).
Staton, C. A. et al. Identification of key residues involved in mediating the in vivo anti-tumor/anti-endothelial activity of Alphastatin. J. Thromb. Haemost. 5, 846–854 (2007).
Osada, T. et al. In vivo detection of HSP90 identifies breast cancers with aggressive behaviour. Clin. Cancer Res. 23, 7531–7542 (2017).
Harnoss, J. M. et al. IRE1α disruption in triple-negative breast cancer cooperates with antiangiogenic therapy by reversing ER stress adaptation and remodeling the tumor microenvironment. Cancer Res. 80, 2368–2379 (2020).
Masiero, M. et al. Development of therapeutic anti-JAGGED1 antibodies for cancer therapy. Mol. Cancer Ther. 18, 2030–2042 (2019).
Sudhan, D. R. et al. Extended adjuvant therapy with neratinib plus fulvestrant blocks ER/HER2 crosstalk and maintains complete responses of ER+/HER2+ breast cancers: implications to the ExteNET trial. Clin. Cancer Res. 25, 771–783 (2019).
Stribbling, S. M. et al. Regressions of established breast carcinoma xenografts by carboxypeptidase G2 suicide gene therapy and the prodrug CMDA are due to a bystander effect. Hum. Gene Ther. 11, 285–292 (2000).
Kennedy, S. P. et al. Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer. Oncogene 39, 3028–3040 (2020).
Chen, F. et al. Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer. Nat. Commun. 9, 4141–4152 (2018).
Hiraki, M. et al. Targeting MUC1-C suppresses BCL2A1 in triple-negative breast cancer. Sig. Transduct. Target Ther. 3, 13–20 (2018).
Kumar, M., Yigit, M., Dai, G., Moore, A. & Medarova, Z. Image-guided breast tumor therapy using a small interfering RNA nanodrug. Cancer Res. 70, 7553–7561 (2010).
Sultan, A. S. et al. Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene 24, 746–760 (2005).
Iwata, T. N. et al. A HER2-targeting antibody-drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model. Mol. Cancer Ther. 17, 1494–1503 (2018).
Ayan, D., Maltais, R., Roy, J. & Poirier, D. A new nonestrogenic steroidal inhibitor of 17β-hydroxysteroid dehydrogenase type I blocks the estrogen-dependent breast cancer tumor growth induced by estrone. Mol. Cancer Ther. 11, 2096–2104 (2012).
Theodossiou, T. A. et al. Simultaneous defeat of MCF7 and MDA-MB-231 resistances by a hypericin PDT–tamoxifen hybrid therapy. NPJ Breast Cancer 5, 13–22 (2019).
Elmi, A. et al. Cell-proliferation imaging for monitoring response to CDK4/6 inhibition combined with endocrine-therapy in breast cancer: comparison of [18F]FLT and [18F]ISO-1 PET/CT. Clin. Cancer Res. 25, 3063–3073 (2019).
Cappuccini, F., Stribbling, S., Pollock, E., Hill, A. V. S. & Redchenko, I. Immunogenicity and efficacy of the novel cancer vaccine based on simian adenovirus and MVA vectors alone and in combination with PD-1 mAb in a mouse model of prostate cancer. Cancer Immunol. Immunother. 65, 701–713 (2016).
Philippou, Y. et al. Impacts of combining anti-PD-L1 immunotherapy and radiotherapy on the tumour immune microenvironment in a murine prostate cancer model. Br. J. Cancer 123, 1089–1100 (2020).
Zheng, X. et al. Atorvastatin and celecoxib inhibit prostate PC-3 tumors in immunodeficient mice. Clin. Cancer Res. 13, 5480–5487 (2007).
Chan, Q. K. Y. et al. Activation of GPR30 inhibits the growth of prostate cancer cells through sustained activation of Erk1/2, c-jun/c-fos-dependent upregulation of p21, and induction of G2 cell-cycle arrest. Cell Death Differ. 17, 1511–1523 (2010).
Bansal, N. et al. Darinaparsin inhibits prostate tumor–initiating cells and Du145 xenografts and is an inhibitor of hedgehog signaling. Mol. Cancer Ther. 14, 23–30 (2015).
Yan, J., De Melo, J., Cutz., J.-C., Aziz, T. & Tang, D. Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis. Br. J. Cancer 110, 2593–2603 (2014).
Tang, Y. et al. Docetaxel followed by castration improves outcomes in LNCaP prostate cancer–bearing severe combined immunodeficient mice. Clin. Cancer Res. 12, 169–174 (2006).
Welén, K., Jennbacken, K., Tes̆an, T. & Damber, J.-E. Pericyte coverage decreases invasion of tumour cells into blood vessels in prostate cancer xenografts. Prostate Cancer Prostatic Dis. 12, 41–46 (2009).
Marshall, N. A. et al. Immunotherapy with PI3K inhibitor and toll-like receptor agonist induces IFN-γ+IL-17+ polyfunctional T cells that mediate rejection of murine tumors. Cancer Res. 72, 581–591 (2012).
Kim, D. H. et al. Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer. Exp. Mol. Med. 51, 1–13 (2019).
Zhang, X. et al. Targeting CD47 and autophagy elicited enhanced antitumor effects in non–small cell lung cancer. Cancer Immunol. Res. 5, 363–375 (2017).
Fan, J. et al. Bruceine D induces lung cancer cell apoptosis and autophagy via the ROS/MAPK signaling pathway in vitro and in vivo. Cell Death Dis. 11, 126–140 (2020).
Rho, J. K. et al. Combined treatment with silibinin and epidermal growth factor receptor tyrosine kinase inhibitors overcomes drug resistance caused by T790M mutation. Mol. Cancer Ther. 9, 323–343 (2010).
Yamaoka, T. et al. Distinct afatinib resistance mechanisms identified in lung adenocarcinoma harboring an EGFR mutation. Mol. Cancer Res. 15, 915–928 (2017).
Whalen, K. A. et al. Targeting the somatostatin receptor 2 with the miniaturized drug conjugate, PEN-221: a potent and novel therapeutic for the treatment of small cell lung cancer. Mol. Cancer Ther. 18, 1926–1936 (2019).
Hirt, U. A. et al. Efficacy of the highly selective focal adhesion kinase inhibitor BI 853520 in adenocarcinoma xenograft models is linked to a mesenchymal tumor phenotype. Oncogenesis 7, 21–31 (2018).
de Almeida, P. E. et al. Anti-VEGF treatment enhances CD8+ T-cell antitumor activity by amplifying hypoxia. Cancer Immunol. Res. 8, 806–818 (2020).
Govindan, S. V., Cardillo, T. M., Moon, S. J., Hansen, H. J. & Goldenberg, D. M. CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin. Cancer Res. 15, 6052–6061 (2009).
Chiacchiera, F. et al. p38α blockade inhibits colorectal cancer growth in vivo by inducing a switch from HIF1α- to FoxO-dependent transcription. Cell Death Differ. 16, 1203–1214 (2009).
Ruiz de Sabando, A. et al. ML264, A novel small-molecule compound that potently inhibits growth of colorectal cancer. Mol. Cancer Ther. 15, 72–83 (2016).
Takahashi, T., Kanazawa, J., Akinaga, S., Tamaoki, T. & Okabe, M. Antitumor activity of 2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl) adenine, a novel deoxyadenosine analog, against human colon tumor xenografts by oral administration. Cancer Chemother. Pharmacol. 43, 233–240 (1999).
Englinger, B. et al. Loss of CUL4A expression is underlying cisplatin hypersensitivity in colorectal carcinoma cells with acquired trabectedin resistance. Br. J. Cancer 116, 489–500 (2017).
Hingorani, D. V. et al. Precision chemoradiotherapy for HER2 tumors using antibody conjugates of an auristatin derivative with reduced cell permeability. Mol. Cancer Ther. 19, 157–167 (2020).
Rebecca, V. W. et al. PPT1 promotes tumor growth and is the molecular target of chloroquine derivatives in cancer. Cancer Discov. 9, 396–415 (2019).
Shepelytskyi, Y. et al. In-vivo retention of 5-fluorouracil using 19F magnetic resonance chemical shift imaging in colorectal cancer in a murine model. Sci. Rep. 9, 13244 (2019).
Byth, K. F. et al. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol. Cancer Ther. 8, 1856–1866 (2009).
Papaevangelou, E., Almeida, G. S., Jamin, Y., Robinson, S. P. & deSouza, N. M. Diffusion-weighted MRI for imaging cell death after cytotoxic or apoptosis-inducing therapy. Br. J. Cancer 112, 1471–1479 (2015).
Singhal, S. S. et al. A target for kidney cancer therapy. Cancer Res. 69, 4244–4251 (2009).
Kumar, R. et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol. Cancer Ther. 6, 2012–2021 (2007).
Dasgupta, P. et al. MicroRNA-203 inhibits long noncoding RNA HOTAIR and regulates tumorigenesis through epithelial-to-mesenchymal transition pathway in renal cell carcinoma. Mol. Cancer Ther. 17, 1061–1069 (2108).
Gerdes, C. A. et al. GA201 (RG7160): a novel, humanized glycoengineered anti-EGFR antibody with enhanced ADCC and superior in vivo efficacy compared with cetuximab. Clin. Cancer Res. 19, 1126–1138 (2006).
Matsuki, M. et al. Lenvatinib inhibits angiogenesis and tumor fibroblast growth factor signalling pathways in human hepatocellular carcinoma models. Cancer Med. 7, 2641–2653 (2018).
Pu, J. et al. ADORA2A-AS1 restricts hepatocellular carcinoma progression via binding HuR and repressing FSCN1/AKT axis. Front. Oncol. 11, 754835 (2021).
Eng, C. H. et al. Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy. Proc. Natl. Acad. Sci. USA. 113, 182–187 (2016).
Xiao, Q. et al. Cancer-associated fibroblasts in pancreatic cancer are reprogrammed by tumor-induced alterations in genomic DNA methylation. Cancer Res. 76, 5395–5404 (2021).
Yang, L. et al. Targeting interleukin-4 receptor a with hybrid peptide for effective cancer therapy. Mol. Cancer Ther. 11, 235–243 (2011).
Tonra, J. R. et al. Synergistic antitumor effects of combined epidermal growth factor receptor and vascular endothelial growth factor receptor-2 targeted therapy. Clin. Cancer Res. 12, 2197–2207 (2006).
Lee, S. J. et al. Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo. BMC Cancer 11, 144–156 (2011).
Li, X.-N. et al. Valproic acid induces growth arrest, apoptosis, and senescence in medulloblastomas by increasing histone hyperacetylation and regulating. Mol. Cancer Ther. 4, 1912–1922 (2005).
Lee, S. Y. et al. Characterization of a novel anti-cancer compound for astrocytomas. PLoS One 9, e108166 (2014).
Li, T. et al. Phospholipase Cγ1 (PLCG1) overexpression is associated with tumor growth and poor survival in IDH wild-type lower-grade gliomas in adult patients. Lab Invest. 102, 143–153 (2022).
Sanchez, I. M. et al. In vivo ERK 1/2 reporter predictively models response and resistance to combined BRAF and MEK inhibitors in melanoma. Mol. Cancer Ther. 18, 1637–1648 (2019).
Segat, G. C. et al. A new series of acetohydroxamates shows in vitro and in vivo anticancer activity against melanoma. Invest. N. Drugs 38, 977–989 (2020).
Garton, A. J. et al. OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res. 66, 1015–1024 (2006).
Beitz, J. G. et al. Antitumor activity of basic fibroblast growth factor-saporin mitotoxin in vitro and in vivo. Cancer Res. 52, 227–230 (1992).
Fung, A. S., Yu, M., Ye, Q. J. & Tannock, I. F. Scheduling of paclitaxel and gefitinib to inhibit repopulation for optimal treatment of human cancer cells and xenografts that overexpress the epidermal growth factor receptor. Cancer Chemother. Pharmacol. 72, 585–595 (2013).
Anand, S. et al. Fluorouracil enhances photodynamic therapy of squamous cell carcinoma via a p53-independent mechanism that increases protoporphyrin IX levels and tumor cell death. Mol. Cancer Ther. 16, 1092–1101 (2017).
Morris, J. et al. F-aza-T-dCyd (NSC801845), a novel cytidine analog, in comparative cell culture and xenograft studies with the clinical candidates T-dCyd, F-T-dCyd, and Aza-T-dCyd. Mol. Cancer Ther. 20, 625–631 (2021).
Molthoff, C. F. M., Pinedo, H. M., Schluper, H. M. M., Rutgers, D. H. & Boven, E. Comparison of 131I-labelled anti-episialin 139H2 with cisplatin, cyclophosphamide or external-beam radiation for anti-tumor efficacy in human ovarian cancer xenografts. Int. J. Cancer 51, 108–115 (1992).
Yao, S. et al. Development and evaluation of novel tumor-targeting paclitaxel-loaded nano-carriers for ovarian cancer treatment: in vitro and in vivo. J. Exp. Clin. Cancer Res. 37, 29 (2018).
Bardella, C. et al. The therapeutic potential of hepatocyte growth factor to sensitize ovarian cancer cells to cisplatin and paclitaxel in vivo. Clin. Cancer Res. 13, 2191–2198 (2007).

The cell-line-derived subcutaneous tumor model in preclinical cancer research

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