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Annual Review of Cancer Biology

Volume 4, 2020

Investigating Tumor Heterogeneity in Mouse Models

Abstract

Cancer arises from a single cell through a series of acquired mutations and epigenetic alterations. Tumors gradually develop into a complex tissue comprised of phenotypically heterogeneous cancer cell populations, as well as noncancer cells that make up the tumor microenvironment. The phenotype, or state, of each cancer and stromal cell is influenced by a plethora of cell-intrinsic and cell-extrinsic factors. The diversity of these cellular states promotes tumor progression, enables metastasis, and poses a challenge for effective cancer treatments. Thus, the identification of strategies for the therapeutic manipulation of tumor heterogeneity would have significant clinical implications. A major barrier in the field is the difficulty in functionally investigating heterogeneity in tumors in cancer patients. Here we review how mouse models of human cancer can be leveraged to interrogate tumor heterogeneity and to help design better therapeutic strategies.

Keyword(s): cancer stem cells, epigenetics, genetics, mouse models, tumor heterogeneity, tumor microenvironment
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2020-03-04
2024-04-26
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Literature Cited

  1. Aiello NM, Maddipati R, Norgard RJ, Balli D, Li J et al. 2018. EMT subtype influences epithelial plasticity and mode of cell migration. Dev. Cell 45:681–95.e4
     [Google Scholar]
  2. Akbay EA, Kim J. 2018. Autochthonous murine models for the study of smoker and never-smoker associated lung cancers. Transl. Lung Cancer Res. 7:464–86
     [Google Scholar]
  3. Assenov Y, Brocks D, Gerhauser C 2018. Intratumor heterogeneity in epigenetic patterns. Semin. Cancer Biol. 51:12–21
     [Google Scholar]
  4. Balkwill FR, Capasso M, Hagemann T 2012. The tumor microenvironment at a glance. J. Cell Sci. 125:5591–96
     [Google Scholar]
  5. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M et al. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. . Nature 449:1003–7
     [Google Scholar]
  6. Batlle E, Clevers H. 2017. Cancer stem cells revisited. Nat. Med. 23:1124–34
     [Google Scholar]
  7. Ben-David U, Beroukhim R, Golub TR 2019. Genomic evolution of cancer models: perils and opportunities. Nat. Rev. Cancer 19:97–109
     [Google Scholar]
  8. Brady JJ, Chuang CH, Greenside PG, Rogers ZN, Murray CW et al. 2016. An Arntl2-driven secretome enables lung adenocarcinoma metastatic self-sufficiency. Cancer Cell 29:697–710
     [Google Scholar]
  9. Buch T, Heppner FL, Tertilt C, Heinen TJ, Kremer M et al. 2005. A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration. Nat. Methods 2:419–26
     [Google Scholar]
  10. Calbo J, van Montfort E, Proost N, van Drunen E, Beverloo HB et al. 2011. A functional role for tumor cell heterogeneity in a mouse model of small cell lung cancer. Cancer Cell 19:244–56
     [Google Scholar]
  11. Caswell DR, Chuang CH, Ma RK, Winters IP, Snyder EL, Winslow MM 2018. Tumor suppressor activity of Selenbp1, a direct Nkx2-1 target, in lung adenocarcinoma. Mol. Cancer Res. 16:1737–49
     [Google Scholar]
  12. Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM et al. 2017. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 9:34
     [Google Scholar]
  13. Chen J, Li Y, Yu TS, McKay RM, Burns DK et al. 2012. A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:522–26
     [Google Scholar]
  14. Chuang CH, Greenside PG, Rogers ZN, Brady JJ, Yang D et al. 2017. Molecular definition of a metastatic lung cancer state reveals a targetable CD109–Janus kinase–Stat axis. Nat. Med. 23:291–300
     [Google Scholar]
  15. Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH et al. 2006. Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 66:9339–44
     [Google Scholar]
  16. Cobbold SP, Jayasuriya A, Nash A, Prospero TD, Waldmann H 1984. Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature 312:548–51
     [Google Scholar]
  17. Dagogo-Jack I, Shaw AT. 2018. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 15:81–94
     [Google Scholar]
  18. Daley JM, Thomay AA, Connolly MD, Reichner JS, Albina JE 2008. Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J. Leukoc. Biol. 83:64–70
     [Google Scholar]
  19. Datlinger P, Rendeiro AF, Schmidl C, Krausgruber T, Traxler P et al. 2017. Pooled CRISPR screening with single-cell transcriptome readout. Nat. Methods 14:297–301
     [Google Scholar]
  20. de Ruiter JR, Wessels LFA, Jonkers J 2018. Mouse models in the era of large human tumour sequencing studies. Open. Biol. 8:180080
     [Google Scholar]
  21. de Sousa e Melo F, Kurtova AV, Harnoss JM, Kljavin N, Hoeck JD et al. 2017. A distinct role for Lgr5+ stem cells in primary and metastatic colon cancer. Nature 543:676–80
     [Google Scholar]
  22. Denny SK, Yang D, Chuang CH, Brady JJ, Lim JS et al. 2016. Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell 166:328–42
     [Google Scholar]
  23. Dixit A, Parnas O, Li B, Chen J, Fulco CP et al. 2016. Perturb-seq: dissecting molecular circuits with scalable single-cell RNA profiling of pooled genetic screens. Cell 167:1853–66.e17
     [Google Scholar]
  24. Easwaran H, Tsai HC, Baylin SB 2014. Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol. Cell 54:716–27
     [Google Scholar]
  25. Eng CL, Lawson M, Zhu Q, Dries R, Koulena N et al. 2019. Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature 568:235–39
     [Google Scholar]
  26. Fargion S, Carney D, Mulshine J, Rosen S, Bunn P et al. 1986. Heterogeneity of cell surface antigen expression of human small cell lung cancer detected by monoclonal antibodies. Cancer Res 46:2633–38
     [Google Scholar]
  27. Fidler IJ, Kim SJ, Langley RR 2007. The role of the organ microenvironment in the biology and therapy of cancer metastasis. J. Cell. Biochem. 101:927–36
     [Google Scholar]
  28. Frese KK, Tuveson DA. 2007. Maximizing mouse cancer models. Nat. Rev. Cancer 7:645–58
     [Google Scholar]
  29. Ge Y, Gomez NC, Adam RC, Nikolova M, Yang H et al. 2017. Stem cell lineage infidelity drives wound repair and cancer. Cell 169:636–50.e14
     [Google Scholar]
  30. George J, Lim JS, Jang SJ, Cun Y, Ozretic L et al. 2015. Comprehensive genomic profiles of small cell lung cancer. Nature 524:47–53
     [Google Scholar]
  31. Gilbertson RJ. 2011. Mapping cancer origins. Cell 145:25–29
     [Google Scholar]
  32. Goltsev Y, Samusik N, Kennedy-Darling J, Bhate S, Hale M et al. 2018. Deep profiling of mouse splenic architecture with CODEX multiplexed imaging. Cell 174:968–81.e15
     [Google Scholar]
  33. Gomez-Cuadrado L, Tracey N, Ma R, Qian B, Brunton VG 2017. Mouse models of metastasis: progress and prospects. Dis. Model. Mech. 10:1061–74
     [Google Scholar]
  34. Gradinaru V, Treweek J, Overton K, Deisseroth K 2018. Hydrogel-tissue chemistry: principles and applications. Annu. Rev. Biophys. 47:355–76
     [Google Scholar]
  35. Grobner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K et al. 2018. The landscape of genomic alterations across childhood cancers. Nature 555:321–27
     [Google Scholar]
  36. Hann B, Balmain A. 2001. Building ‘validated’ mouse models of human cancer. Curr. Opin. Cell Biol. 13:778–84
     [Google Scholar]
  37. Herring CA, Chen B, McKinley ET, Lau KS 2018. Single-cell computational strategies for lineage reconstruction in tissue systems. Cell Mol. Gastroenterol. Hepatol. 5:539–48
     [Google Scholar]
  38. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB et al. 2005. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7:469–83
     [Google Scholar]
  39. Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG et al. 2014. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat. Med. 20:897–903
     [Google Scholar]
  40. Hong MK, Macintyre G, Wedge DC, Van Loo P, Patel K et al. 2015. Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer. Nat. Commun. 6:6605
     [Google Scholar]
  41. Hsueh B, Burns VM, Pauerstein P, Holzem K, Ye L et al. 2017. Pathways to clinical CLARITY: volumetric analysis of irregular, soft, and heterogeneous tissues in development and disease. Sci. Rep. 7:5899
     [Google Scholar]
  42. Hunter KW, Amin R, Deasy S, Ha NH, Wakefield L 2018. Genetic insights into the morass of metastatic heterogeneity. Nat. Rev. Cancer 18:211–23
     [Google Scholar]
  43. Jahchan NS, Lim JS, Bola B, Morris K, Seitz G et al. 2016. Identification and targeting of long-term tumor-propagating cells in small cell lung cancer. Cell Rep 16:644–56
     [Google Scholar]
  44. Jaks V, Barker N, Kasper M, van Es JH, Snippert HJ et al. 2008. Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat. Genet. 40:1291–99
     [Google Scholar]
  45. Jamal-Hanjani M, Hackshaw A, Ngai Y, Shaw J, Dive C et al. 2014. Tracking genomic cancer evolution for precision medicine: the lung TRACERx study. PLOS Biol 12:e1001906
     [Google Scholar]
  46. Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su MJ et al. 2018. A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade. Cell 175:984–97.e24
     [Google Scholar]
  47. Kastenhuber ER, Lalazar G, Houlihan SL, Tschaharganeh DF, Baslan T et al. 2017. DNAJB1–PRKACA fusion kinase interacts with β-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma. PNAS 114:13076–84
     [Google Scholar]
  48. Kebschull JM, Zador AM. 2018. Cellular barcoding: lineage tracing, screening and beyond. Nat. Methods 15:871–79
     [Google Scholar]
  49. Keren L, Bosse M, Marquez D, Angoshtari R, Jain S et al. 2018. A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174:1373–87.e19
     [Google Scholar]
  50. Kester L, van Oudenaarden A 2018. Single-cell transcriptomics meets lineage tracing. Cell Stem Cell 23:166–79
     [Google Scholar]
  51. Khanna C, Hunter K. 2005. Modeling metastasis in vivo. Carcinogenesis 26:513–23
     [Google Scholar]
  52. Ku SY, Rosario S, Wang Y, Mu P, Seshadri M et al. 2017. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 355:78–83
     [Google Scholar]
  53. Kwon MC, Proost N, Song JY, Sutherland KD, Zevenhoven J, Berns A 2015. Paracrine signaling between tumor subclones of mouse SCLC: a critical role of ETS transcription factor Pea3 in facilitating metastasis. Genes Dev 29:1587–92
     [Google Scholar]
  54. Kwong LN, Zou L, Chagani S, Pedamallu CS, Liu M et al. 2017. Modeling genomic instability and selection pressure in a mouse model of melanoma. Cell Rep 19:1304–12
     [Google Scholar]
  55. La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H et al. 2018. RNA velocity of single cells. Nature 560:494–98
     [Google Scholar]
  56. Lambert AW, Pattabiraman DR, Weinberg RA 2017. Emerging biological principles of metastasis. Cell 168:670–91
     [Google Scholar]
  57. Latil M, Nassar D, Beck B, Boumahdi S, Wang L et al. 2017. Cell-type-specific chromatin states differentially prime squamous cell carcinoma tumor-initiating cells for epithelial to mesenchymal transition. Cell Stem Cell 20:191–204.e5
     [Google Scholar]
  58. Lee JW, Komar CA, Bengsch F, Graham K, Beatty GL 2016. Genetically engineered mouse models of pancreatic cancer: the KPC model (LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre), its variants, and their application in immuno-oncology drug discovery. Curr. Protoc. Pharmacol. 73:14 39 1–20
     [Google Scholar]
  59. Li CM, Chen G, Dayton TL, Kim-Kiselak C, Hoersch S et al. 2013. Differential Tks5 isoform expression contributes to metastatic invasion of lung adenocarcinoma. Genes Dev 27:1557–67
     [Google Scholar]
  60. Lim JS, Ibaseta A, Fischer MM, Cancilla B, O'Young G et al. 2017. Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer. Nature 545:360–64
     [Google Scholar]
  61. Ludwig LS, Lareau CA, Ulirsch JC, Christian E, Muus C et al. 2019. Lineage tracing in humans enabled by mitochondrial mutations and single-cell genomics. Cell 176:1325–39.e22
     [Google Scholar]
  62. Magee JA, Piskounova E, Morrison SJ 2012. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 21:283–96
     [Google Scholar]
  63. Marusyk A, Almendro V, Polyak K 2012. Intra-tumour heterogeneity: a looking glass for cancer?. Nat. Rev. Cancer 12:323–34
     [Google Scholar]
  64. Marusyk A, Polyak K. 2010. Tumor heterogeneity: causes and consequences. Biochim. Biophys. Acta 1805:105–17
     [Google Scholar]
  65. McCreery MQ, Halliwill KD, Chin D, Delrosario R, Hirst G et al. 2015. Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers. Nat. Med. 21:1514–20
     [Google Scholar]
  66. McFadden DG, Papagiannakopoulos T, Taylor-Weiner A, Stewart C, Carter SL et al. 2014. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell 156:1298–311
     [Google Scholar]
  67. McGranahan N, Swanton C. 2017. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell 168:613–28
     [Google Scholar]
  68. McIlhatton MA, Boivin GP, Groden J 2016. Manipulation of DNA repair proficiency in mouse models of colorectal cancer. Biomed. Res. Int. 2016:1414383
     [Google Scholar]
  69. McKenna A, Findlay GM, Gagnon JA, Horwitz MS, Schier AF, Shendure J 2016. Whole-organism lineage tracing by combinatorial and cumulative genome editing. Science 353:aaf7907
     [Google Scholar]
  70. Meacham CE, Morrison SJ. 2013. Tumour heterogeneity and cancer cell plasticity. Nature 501:328–37
     [Google Scholar]
  71. Moffitt JR, Zhuang X. 2016. RNA imaging with multiplexed error-robust fluorescence in situ hybridization (MERFISH). Methods Enzymol 572:1–49
     [Google Scholar]
  72. Morrissy AS, Cavalli FMG, Remke M, Ramaswamy V, Shih DJH et al. 2017. Spatial heterogeneity in medulloblastoma. Nat. Genet. 49:780–88
     [Google Scholar]
  73. Mu P, Zhang Z, Benelli M, Karthaus WR, Hoover E et al. 2017. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 355:84–88
     [Google Scholar]
  74. Muzumdar MD, Dorans KJ, Chung KM, Robbins R, Tammela T et al. 2016. Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers. Nat. Commun. 7:12685
     [Google Scholar]
  75. Nagaraj AS, Lahtela J, Hemmes A, Pellinen T, Blom S et al. 2017. Cell of origin links histotype spectrum to immune microenvironment diversity in non-small-cell lung cancer driven by mutant Kras and loss of Lkb1. . Cell Rep 18:673–84
     [Google Scholar]
  76. Nassar D, Blanpain C. 2016. Cancer stem cells: basic concepts and therapeutic implications. Annu. Rev. Pathol. 11:47–76
     [Google Scholar]
  77. Naxerova K, Reiter JG, Brachtel E, Lennerz JK, van de Wetering M et al. 2017. Origins of lymphatic and distant metastases in human colorectal cancer. Science 357:55–60
     [Google Scholar]
  78. Neal JT, Li X, Zhu J, Giangarra V, Grzeskowiak CL et al. 2018. Organoid modeling of the tumor immune microenvironment. Cell 175:1972–88.e16
     [Google Scholar]
  79. Nguyen DX, Massague J. 2007. Genetic determinants of cancer metastasis. Nat. Rev. Genet. 8:341–52
     [Google Scholar]
  80. Niederst MJ, Sequist LV, Poirier JT, Mermel CH, Lockerman EL et al. 2015. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat. Commun. 6:6377
     [Google Scholar]
  81. Nowotschin S, Setty M, Kuo YY, Liu V, Garg V et al. 2019. The emergent landscape of the mouse gut endoderm at single-cell resolution. Nature 569:361–67
     [Google Scholar]
  82. Olson B, Li Y, Lin Y, Liu ET, Patnaik A 2018. Mouse models for cancer immunotherapy research. Cancer Discov 8:1358–65
     [Google Scholar]
  83. Park JW, Lee JK, Sheu KM, Wang L, Balanis NG et al. 2018. Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage. Science 362:91–95
     [Google Scholar]
  84. Perli SD, Cui CH, Lu TK 2016. Continuous genetic recording with self-targeting CRISPR-Cas in human cells. Science 353:aag0511
     [Google Scholar]
  85. Qiu W, Su GH. 2013. Challenges and advances in mouse modeling for human pancreatic tumorigenesis and metastasis. Cancer Metastasis Rev 32:83–107
     [Google Scholar]
  86. Quintana E, Shackleton M, Foster HR, Fullen DR, Sabel MS et al. 2010. Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell 18:510–23
     [Google Scholar]
  87. Rangarajan A, Weinberg RA. 2003. Comparative biology of mouse versus human cells: modelling human cancer in mice. Nat. Rev. Cancer 3:952–59
     [Google Scholar]
  88. Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE et al. 1994. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood 83:435–45
     [Google Scholar]
  89. Reiter JG, Makohon-Moore AP, Gerold JM, Heyde A, Attiyeh MA et al. 2018. Minimal functional driver gene heterogeneity among untreated metastases. Science 361:1033–37
     [Google Scholar]
  90. Rhim AD, Mirek ET, Aiello NM, Maitra A, Bailey JM et al. 2012. EMT and dissemination precede pancreatic tumor formation. Cell 148:349–61
     [Google Scholar]
  91. Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E et al. 2019. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science 363:1463–67
     [Google Scholar]
  92. Rudin CM, Pietanza MC, Bauer TM, Ready N, Morgensztern D et al. 2017. Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate, in recurrent small-cell lung cancer: a first-in-human, first-in-class, open-label, phase 1 study. Lancet Oncol 18:42–51
     [Google Scholar]
  93. Sanchez-Danes A, Larsimont JC, Liagre M, Munoz-Couselo E, Lapouge G et al. 2018. A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy. Nature 562:434–38
     [Google Scholar]
  94. Sanchez-Rivera FJ, Jacks T. 2015. Applications of the CRISPR-Cas9 system in cancer biology. Nat. Rev. Cancer 15:387–95
     [Google Scholar]
  95. Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S et al. 2015. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci. Transl. Med. 7:302ra136
     [Google Scholar]
  96. Scheele C, Maynard C, van Rheenen J 2016. Intravital insights into heterogeneity, metastasis, and therapy responses. Trends Cancer 2:205–16
     [Google Scholar]
  97. Schepers AG, Snippert HJ, Stange DE, van den Born M, van Es JH et al. 2012. Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337:730–35
     [Google Scholar]
  98. Schiebinger G, Shu J, Tabaka M, Cleary B, Subramanian V et al. 2019. Optimal-transport analysis of single-cell gene expression identifies developmental trajectories in reprogramming. Cell 176:928–43.e22
     [Google Scholar]
  99. Seaman WE, Sleisenger M, Eriksson E, Koo GC 1987. Depletion of natural killer cells in mice by monoclonal antibody to NK-1.1: reduction in host defense against malignancy without loss of cellular or humoral immunity. J. Immunol. 138:4539–44
     [Google Scholar]
  100. Semenova EA, Kwon MC, Monkhorst K, Song JY, Bhaskaran R et al. 2016. Transcription factor NFIB is a driver of small cell lung cancer progression in mice and marks metastatic disease in patients. Cell Rep 16:631–43
     [Google Scholar]
  101. Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB et al. 2011. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med. 3:75ra26
     [Google Scholar]
  102. Setty M, Tadmor MD, Reich-Zeliger S, Angel O, Salame TM et al. 2016. Wishbone identifies bifurcating developmental trajectories from single-cell data. Nat. Biotechnol. 34:637–45
     [Google Scholar]
  103. Shackleton M, Quintana E, Fearon ER, Morrison SJ 2009. Heterogeneity in cancer: cancer stem cells versus clonal evolution. Cell 138:822–29
     [Google Scholar]
  104. Shakiba N, Fahmy A, Jayakumaran G, McGibbon S, David L et al. 2019. Cell competition during reprogramming gives rise to dominant clones. Science 364:eaan0925
     [Google Scholar]
  105. Shimokawa M, Ohta Y, Nishikori S, Matano M, Takano A et al. 2017. Visualization and targeting of LGR5+ human colon cancer stem cells. Nature 545:187–92
     [Google Scholar]
  106. Socinski MA, Kaye FJ, Spigel DR, Kudrik FJ, Ponce S et al. 2017. Phase 1/2 study of the CD56-targeting antibody-drug conjugate lorvotuzumab mertansine (IMGN901) in combination with carboplatin/etoposide in small-cell lung cancer patients with extensive-stage disease. Clin. Lung Cancer 18:68–76.e2
     [Google Scholar]
  107. Spanjaard B, Hu B, Mitic N, Olivares-Chauvet P, Janjuha S et al. 2018. Simultaneous lineage tracing and cell-type identification using CRISPR-Cas9-induced genetic scars. Nat. Biotechnol. 36:469–73
     [Google Scholar]
  108. Spanjaard B, Junker JP. 2017. Methods for lineage tracing on the organism-wide level. Curr. Opin. Cell Biol. 49:16–21
     [Google Scholar]
  109. Stahl PL, Salmen F, Vickovic S, Lundmark A, Navarro JF et al. 2016. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353:78–82
     [Google Scholar]
  110. Sutherland KD, Song JY, Kwon MC, Proost N, Zevenhoven J, Berns A 2014. Multiple cells-of-origin of mutant K-Ras-induced mouse lung adenocarcinoma. PNAS 111:4952–57
     [Google Scholar]
  111. Tammela T, Sanchez-Rivera FJ, Cetinbas NM, Wu K, Joshi NS et al. 2017. A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma. Nature 545:355–59
     [Google Scholar]
  112. Tanay A, Regev A. 2017. Scaling single-cell genomics from phenomenology to mechanism. Nature 541:331–38
     [Google Scholar]
  113. Tian H, Biehs B, Warming S, Leong KG, Rangell L et al. 2011. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478:255–59
     [Google Scholar]
  114. Tredan O, Galmarini CM, Patel K, Tannock IF 2007. Drug resistance and the solid tumor microenvironment. J. Natl. Cancer Inst. 99:1441–54
     [Google Scholar]
  115. Turajlic S, Xu H, Litchfield K, Rowan A, Chambers T et al. 2018. Tracking cancer evolution reveals constrained routes to metastases: TRACERx renal. Cell 173:581–94.e12
     [Google Scholar]
  116. van Niekerk G, Davids LM, Hattingh SM, Engelbrecht AM 2017. Cancer stem cells: A product of clonal evolution?. Int. J. Cancer 140:993–99
     [Google Scholar]
  117. van Rooijen N, Sanders A, van den Berg TK 1996. Apoptosis of macrophages induced by liposome-mediated intracellular delivery of clodronate and propamidine. J. Immunol. Methods 193:93–99
     [Google Scholar]
  118. Visvader JE. 2011. Cells of origin in cancer. Nature 469:314–22
     [Google Scholar]
  119. Visvader JE, Lindeman GJ. 2012. Cancer stem cells: current status and evolving complexities. Cell Stem Cell 10:717–28
     [Google Scholar]
  120. Wainwright EN, Scaffidi P. 2017. Epigenetics and cancer stem cells: unleashing, hijacking, and restricting cellular plasticity. Trends Cancer 3:372–86
     [Google Scholar]
  121. Wang G, Lu X, Dey P, Deng P, Wu CC et al. 2016. Targeting YAP-dependent MDSC infiltration impairs tumor progression. Cancer Discov 6:80–95
     [Google Scholar]
  122. Williamson SC, Metcalf RL, Trapani F, Mohan S, Antonello J et al. 2016. Vasculogenic mimicry in small cell lung cancer. Nat. Commun. 7:13322
     [Google Scholar]
  123. Winslow MM, Dayton TL, Verhaak RG, Kim-Kiselak C, Snyder EL et al. 2011. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473:101–4
     [Google Scholar]
  124. Wong E, Yang K, Kuraguchi M, Werling U, Avdievich E et al. 2002. Mbd4 inactivation increases C→T transition mutations and promotes gastrointestinal tumor formation. PNAS 99:14937–42
     [Google Scholar]
  125. Wu N, Jia D, Ibrahim AH, Bachurski CJ, Gronostajski RM, MacPherson D 2016. NFIB overexpression cooperates with Rb/p53 deletion to promote small cell lung cancer. Oncotarget 7:57514–24
     [Google Scholar]
  126. Xu XL, Singh HP, Wang L, Qi DL, Poulos BK et al. 2014. Rb suppresses human cone-precursor-derived retinoblastoma tumours. Nature 514:385–88
     [Google Scholar]
  127. Yang D, Denny SK, Greenside PG, Chaikovsky AC, Brady JJ et al. 2018. Intertumoral heterogeneity in SCLC is influenced by the cell type of origin. Cancer Discov 8:1316–31
     [Google Scholar]
  128. Zhang X, Marjani SL, Hu Z, Weissman SM, Pan X, Wu S 2016. Single-cell sequencing for precise cancer research: progress and prospects. Cancer Res 76:1305–12
     [Google Scholar]
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Investigating Tumor Heterogeneity in Mouse Models
Annual Review of Cancer Biology 4, 99 (2020); https://doi.org/10.1146/annurev-cancerbio-030419-033413
/content/journals/10.1146/annurev-cancerbio-030419-033413
/content/journals/10.1146/annurev-cancerbio-030419-033413
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