Biology and evolution of poorly differentiated neuroendocrine tumors

Nature Medicine

Volumn 23, Issue 6, 2017, Pages 664-673

  Rickman, David S ^a,b   Beltran, Himisha ^a,b   Demichelis, Francesca ^a,b,c   Rubin, Mark A ^a,b  

^a NEW YORK PRESBYTERIAN HOSPITAL   (United States)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

^c UNIVERSITY OF TRENTO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

CARCINOGENESIS; CELL LINEAGE; CELL PLASTICITY; EPIGENETICS; GENOMICS; HUMAN; NEUROENDOCRINE TUMOR; NONHUMAN; POORLY DIFFERENTIATED NEUROENDOCRINE TUMOR; PRIORITY JOURNAL; REVIEW; CARCINOMA, NEUROENDOCRINE; CARCINOMA, SMALL CELL; CELL DIFFERENTIATION; COLONIC NEOPLASMS; DISEASE COURSE; ESOPHAGEAL NEOPLASMS; FEMALE; GENETIC EPIGENESIS; GENETICS; HEAD AND NECK NEOPLASMS; LUNG NEOPLASMS; MALE; MOLECULARLY TARGETED THERAPY; NEOPLASM; NEUROENDOCRINE TUMORS; OVARIAN NEOPLASMS; PROSTATIC NEOPLASMS; URINARY BLADDER NEOPLASMS; UTERINE CERVICAL NEOPLASMS;

(+)-JQ1 COMPOUND; ALISERTIB; ANTINEOPLASTIC AGENT; AZEPINE DERIVATIVE; BENZODIAZEPINE DERIVATIVE; MET PROTEIN, HUMAN; MOLIBRESIB; MONOCLONAL ANTIBODY; MYC PROTEIN; MYC PROTEIN, HUMAN; PEMBROLIZUMAB; PROTEIN P53; PYRIMIDINE DERIVATIVE; RB1 PROTEIN, HUMAN; RETINOBLASTOMA BINDING PROTEIN; SCATTER FACTOR RECEPTOR; TP53 PROTEIN, HUMAN; TRIAZOLE DERIVATIVE; UBIQUITIN PROTEIN LIGASE;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; AZEPINES; BENZODIAZEPINES; CARCINOGENESIS; CARCINOMA, NEUROENDOCRINE; CARCINOMA, SMALL CELL; CELL DIFFERENTIATION; CELL LINEAGE; CELL PLASTICITY; COLONIC NEOPLASMS; DISEASE PROGRESSION; EPIGENESIS, GENETIC; ESOPHAGEAL NEOPLASMS; FEMALE; HEAD AND NECK NEOPLASMS; HUMANS; LUNG NEOPLASMS; MALE; MOLECULAR TARGETED THERAPY; NEOPLASMS, GLANDULAR AND EPITHELIAL; NEUROENDOCRINE TUMORS; OVARIAN NEOPLASMS; PROSTATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-MET; PROTO-ONCOGENE PROTEINS C-MYC; PYRIMIDINES; RETINOBLASTOMA BINDING PROTEINS; TRIAZOLES; TUMOR SUPPRESSOR PROTEIN P53; UBIQUITIN-PROTEIN LIGASES; URINARY BLADDER NEOPLASMS; UTERINE CERVICAL NEOPLASMS;

EID: 85020278745     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.4341     Document Type: Review

References (139)

1. Perren, A. et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: pathology: diagnosis and prognostic stratification. Neuroendocrinology http://dx.doi.org/10.1159/000457956 (2017).
2. Ferrone, C.R. et al. Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified? J. Clin. Oncol. 25, 5609-5615 (2007).
3. Hochwald, S.N. et al. Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade and intermediate-grade groups. J. Clin. Oncol. 20, 2633-2642 (2002).
4. Liu, T.C., Hamilton, N., Hawkins, W., Gao, F. & Cao, D. Comparison of WHO Classifications (2004, 2010), the Hochwald grading system, and AJCC and ENETS staging systems in predicting prognosis in locoregional well-differentiated pancreatic neuroendocrine tumors. Am. J. Surg. Pathol. 37, 853-859 (2013).
5. Tang, L.H. et al. Well-differentiated neuroendocrine tumors with a morphologically apparent high-grade component: a pathway distinct from poorly differentiated neuroendocrine carcinomas. Clin. Cancer Res. 22, 1011-1017 (2016).
6. den Bakker, M.A. & Thunnissen, F.B. Neuroendocrine tumours-challenges in the diagnosis and classification of pulmonary neuroendocrine tumours. J. Clin. Pathol. 66, 862-869 (2013).
7. Janson, E.T. et al. Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. Acta Oncol. 53, 1284-1297 (2014).
8. Kidd, M., Modlin, I. & Öberg, K. Towards a new classification of gastroenteropancreatic neuroendocrine neoplasms. Nat. Rev. Clin. Oncol. 13, 691-705 (2016).
9. Priemer, D.S. et al. Neuroendocrine tumors of the prostate: emerging insights from molecular data and updates to the 2016 World Health Organization classification. Endocr. Pathol. 27, 123-135 (2016).
10. Reid, M.D., Balci, S., Saka, B. & Adsay, N.V. Neuroendocrine tumors of the pancreas: current concepts and controversies. Endocr. Pathol. 25, 65-79 (2014).
11. Rouzbahman, M. & Clarke, B. Neuroendocrine tumors of the gynecologic tract: select topics. Semin. Diagn. Pathol. 30, 224-233 (2013).
12. Scarpa, A. et al. Whole-genome landscape of pancreatic neuroendocrine tumours. Nature 543, 65-71 (2017).
13. Mollaoglu, G. et al. MYC drives progression of small cell lung cancer to a variant neuroendocrine subtype with vulnerability to aurora kinase inhibition. Cancer Cell 31, 270-285 (2017).
14. George, J. et al. Comprehensive genomic profiles of small cell lung cancer. Nature 524, 47-53 (2015).
15. Fernandez-Cuesta, L. et al. Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nat. Commun. 5, 3518 (2014).
16. Rekhtman, N. et al. Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets. Clin. Cancer Res. 22, 3618-3629 (2016).
17. Peifer, M. et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat. Genet. 44, 1104-1110 (2012).
18. Beltran, H. et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat. Med. 22, 298-305 (2016).
19. Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543-550 (2014).
20. Ding, L. et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 455, 1069-1075 (2008).
21. Imielinski, M. et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 150, 1107-1120 (2012).
22. Rizvi, N.A. et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124-128 (2015).
23. Tan, H.L. et al. Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. Clin. Cancer Res. 20, 890-903 (2014).
24. Feng, H., Shuda, M., Chang, Y. & Moore, P.S. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319, 1096-1100 (2008).
25. Berman-Booty, L.D. & Knudsen, K.E. Models of neuroendocrine prostate cancer. Endocr. Relat. Cancer 22, R33-R49 (2015).
26. Zhou, Z. et al. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 66, 7889-7898 (2006).
27. Brodeur, G.M. & Castleberry, R.G. Neuroblastoma. in Principles and Practice of Pediatric Oncology (eds. Pizzo, P.A. & Poplack, D.G.) 739-767 (J.B. Lippincott Co., Philadelphia, PA, 1993).
28. Shuda, M. et al. Merkel cell polyomavirus small T antigen induces cancer and embryonic merkel cell proliferation in a transgenic mouse model. PLoS One 10, e0142329 (2015).
29. Spurgeon, M.E., Cheng, J., Bronson, R.T., Lambert, P.F. & DeCaprio, J.A. Tumorigenic activity of merkel cell polyomavirus T antigens expressed in the stratified epithelium of mice. Cancer Res. 75, 1068-1079 (2015).
30. Verhaegen, M.E. et al. Merkel cell polyomavirus small T antigen is oncogenic in transgenic mice. J. Invest. Dermatol. 135, 1415-1424 (2015).
31. Cavallaro, U., Niedermeyer, J., Fuxa, M. & Christofori, G. N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor signalling. Nat. Cell Biol. 3, 650-657 (2001).
32. Cui, M. et al. PTEN is a potent suppressor of small cell lung cancer. Mol. Cancer Res. 12, 654-659 (2014).
33. Kobayashi, S., Okada, S., Hasumi, T., Sato, N. & Fujimura, S. The significance of NSE and CEA as a differentiation marker for the cellular heterogeneity of small cell lung cancer. Tohoku J. Exp. Med. 189, 37-49 (1999).
34. McFadden, D.G. et al. Genetic and clonal dissection of murine small cell lung carcinoma progression by genome sequencing. Cell 156, 1298-1311 (2014).
35. Meuwissen, R. et al. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 4, 181-189 (2003).
36. Schaffer, B.E. et al. Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma. Cancer Res. 70, 3877-3883 (2010).
37. Shibayama, T. et al. Complementary roles of pro-gastrin-releasing peptide (ProGRP) and neuron specific enolase (NSE) in diagnosis and prognosis of small-cell lung cancer (SCLC). Lung Cancer 32, 61-69 (2001).
38. Borromeo, M.D. et al. ASCL1 and NEUROD1 reveal heterogeneity in pulmonary neuroendocrine tumors and regulate distinct genetic programs. Cell Rep. 16, 1259-1272 (2016).
39. Gazdar, A.F. et al. The comparative pathology of genetically engineered mouse models for neuroendocrine carcinomas of the lung. J. Thorac. Oncol. 10, 553-564 (2015).
40. DeCaprio, J.A. et al. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54, 275-283 (1988).
41. Lane, D.P. & Crawford, L.V. T antigen is bound to a host protein in SV40-transformed cells. Nature 278, 261-263 (1979).
42. Linzer, D.I. & Levine, A.J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17, 43-52 (1979).
43. Gingrich, J.R., Barrios, R.J., Foster, B.A. & Greenberg, N.M. Pathologic progression of autochthonous prostate cancer in the TRAMP model. Prostate Cancer Prostatic Dis. 2, 70-75 (1999).
44. Gingrich, J.R. et al. Metastatic prostate cancer in a transgenic mouse. Cancer Res. 56, 4096-4102 (1996).
45. Greenberg, N.M. et al. Prostate cancer in a transgenic mouse. Proc. Natl. Acad. Sci. USA 92, 3439-3443 (1995).
46. Kaplan-Lefko, P.J. et al. Pathobiology of autochthonous prostate cancer in a pre-clinical transgenic mouse model. Prostate 55, 219-237 (2003).
47. Duan, W. et al. Knockin of SV40 Tag oncogene in a mouse adenocarcinoma of the prostate model demonstrates advantageous features over the transgenic model. Oncogene 24, 1510-1524 (2005).
48. Gabril, M.Y. et al. A novel knock-in prostate cancer model demonstrates biology similar to that of human prostate cancer and suitable for preclinical studies. Mol. Ther. 11, 348-362 (2005).
49. Gabril, M.Y. et al. Prostate targeting: PSP94 gene promoter/enhancer region directed prostate tissue-specific expression in a transgenic mouse prostate cancer model. Gene Ther. 9, 1589-1599 (2002).
50. Garabedian, E.M., Humphrey, P.A. & Gordon, J.I. A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells. Proc. Natl. Acad. Sci. USA 95, 15382-15387 (1998).
51. Klezovitch, O. et al. Hepsin promotes prostate cancer progression and metastasis. Cancer Cell 6, 185-195 (2004).
52. Kwabi-Addo, B. et al. Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression. Proc. Natl. Acad. Sci. USA 98, 11563-11568 (2001).
53. Masumori, N. et al. A probasin-large T antigen transgenic mouse line develops prostate adenocarcinoma and neuroendocrine carcinoma with metastatic potential. Cancer Res. 61, 2239-2249 (2001).
54. Perez-Stable, C. et al. Prostate, adrenocortical, and brown adipose tumors in fetal globin/T antigen transgenic mice. Lab. Invest. 74, 363-373 (1996).
55. Berman-Booty, L.D. et al. Extra-prostatic transgene-associated neoplastic lesions in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Toxicol. Pathol. 43, 186-197 (2015).
56. Suttie, A.W. et al. An investigation of the effects of late-onset dietary restriction on prostate cancer development in the TRAMP mouse. Toxicol. Pathol. 33, 386-397 (2005).
57. Tani, Y., Suttie, A., Flake, G.P., Nyska, A. & Maronpot, R.R. Epithelial-stromal tumor of the seminal vesicles in the transgenic adenocarcinoma mouse prostate model. Vet. Pathol. 42, 306-314 (2005).
58. Ku, S.Y. et al. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 355, 78-83 (2017).
59. Martin, P. et al. Prostate epithelial Pten/TP53 loss leads to transformation of multipotential progenitors and epithelial to mesenchymal transition. Am. J. Pathol. 179, 422-435 (2011).
60. Mu, P. et al. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 355, 84-88 (2017).
61. Brodeur, G.M. Neuroblastoma: biological insights into a clinical enigma. Nat. Rev. Cancer 3, 203-216 (2003).
62. Brodeur, G.M., Seeger, R.C., Schwab, M., Varmus, H.E. & Bishop, J.M. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224, 1121-1124 (1984).
63. Kohl, N.E., Gee, C.E. & Alt, F.W. Activated expression of the N-myc gene in human neuroblastomas and related tumors. Science 226, 1335-1337 (1984).
64. Althoff, K. et al. A Cre-conditional MYCN-driven neuroblastoma mouse model as an improved tool for preclinical studies. Oncogene 34, 3357-3368 (2015).
65. Banerjee, S.A., Hoppe, P., Brilliant, M. & Chikaraishi, D.M. 5′ flanking sequences of the rat tyrosine hydroxylase gene target accurate tissue-specific, developmental, and transsynaptic expression in transgenic mice. J. Neurosci. 12, 4460-4467 (1992).
66. Nakamura, T. et al. Deletions and rearrangements of the retinoblastoma gene in hepatocellular carcinoma, insulinoma and some neurogenic tumors as found in a study of 121 tumors. Jpn. J. Clin. Oncol. 21, 325-329 (1991).
67. The, I. et al. Neurofibromatosis type 1 gene mutations in neuroblastoma. Nat. Genet. 3, 62-66 (1993).
68. Weiss, W.A., Aldape, K., Mohapatra, G., Feuerstein, B.G. & Bishop, J.M. Targeted expression of MYCN causes neuroblastoma in transgenic mice. EMBO J. 16, 2985-2995 (1997).
69. Powers, J.T. et al. Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma. Nature 535, 246-251 (2016).
70. Dardenne, E. et al. N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate cancer. Cancer Cell 30, 563-577 (2016).
71. Lee, J.K. et al. N-Myc drives neuroendocrine prostate cancer initiated from human prostate epithelial cells. Cancer Cell 29, 536-547 (2016).
72. Huijbers, I.J. et al. Rapid target gene validation in complex cancer mouse models using re-derived embryonic stem cells. EMBO Mol. Med. 6, 212-225 (2014).
73. Rudin, C.M. & Poirier, J.T. MYC, MAX, and small cell lung cancer. Cancer Discov. 4, 273-274 (2014).
74. Sos, M.L. et al. A framework for identification of actionable cancer genome dependencies in small cell lung cancer. Proc. Natl. Acad. Sci. USA 109, 17034-17039 (2012).
75. Teicher, B.A. Targets in small cell lung cancer. Biochem. Pharmacol. 87, 211-219 (2014).
76. Wistuba, I.I., Gazdar, A.F. & Minna, J.D. Molecular genetics of small cell lung carcinoma. Semin. Oncol. 28 (Suppl. 4), 3-13 (2001).
77. Kim, D.W. et al. Genetic requirement for Mycl and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer. Genes Dev. 30, 1289-1299 (2016).
78. Hofner, T. et al. Development and characteristics of preclinical experimental models for the research of rare neuroendocrine bladder cancer. J. Urol. 190, 2263-2270 (2013).
79. Kong-Beltran, M., Stamos, J. & Wickramasinghe, D. The Sema domain of Met is necessary for receptor dimerization and activation. Cancer Cell 6, 75-84 (2004).
80. Byers, L.A. et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov. 2, 798-811 (2012).
81. Aryee, M.J. et al. DNA methylation alterations exhibit intraindividual stability and interindividual heterogeneity in prostate cancer metastases. Sci. Transl. Med. 5, 169ra10 (2013).
82. Beltran, H. et al. Molecular characterization of neuroendocrine prostate cancer and identification of new drug targets. Cancer Discov. 1, 487-495 (2011).
83. Jelinic, P. et al. Recurrent SMARCA4 mutations in small cell carcinoma of the ovary. Nat. Genet. 46, 424-426 (2014).
84. Ramos, P. et al. Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4. Nat. Genet. 46, 427-429 (2014).
85. Poirier, J.T. et al. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2. Oncogene 34, 5869-5878 (2015).
86. Pearse, A.G. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J. Histochem. Cytochem. 17, 303-313 (1969).
87. Fontaine, J. & Le Douarin, N.M. Analysis of endoderm formation in the avian blastoderm by the use of quail-chick chimaeras. The problem of the neurectodermal origin of the cells of the APUD series. J. Embryol. Exp. Morphol. 41, 209-222 (1977).
88. Rosai, J. The origin of neuroendocrine tumors and the neural crest saga. Mod. Pathol. 24 (Suppl. 2), S53-S57 (2011).
89. Yachida, S. et al. Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors. Am. J. Surg. Pathol. 36, 173-184 (2012).
90. Brenner, B., Tang, L.H., Shia, J., Klimstra, D.S. & Kelsen, D.P. Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach. Semin. Oncol. 34, 43-50 (2007).
91. Shia, J. et al. Is nonsmall cell type high-grade neuroendocrine carcinoma of the tubular gastrointestinal tract a distinct disease entity? Am. J. Surg. Pathol. 32, 719-731 (2008).
92. Oser, M.G., Niederst, M.J., Sequist, L.V. & Engelman, J.A. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 16, e165-e172 (2015).
93. Niederst, M.J. et al. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat. Commun. 6, 6377 (2015).
94. Sequist, L.V. et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl. Med. 3, 75ra26 (2011).
95. Ohashi, K., Maruvka, Y.E., Michor, F. & Pao, W. Epidermal growth factor receptor tyrosine kinase inhibitor-resistant disease. J. Clin. Oncol. 31, 1070-1080 (2013).
96. Bean, J. et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl. Acad. Sci. USA 104, 20932-20937 (2007).
97. Engelman, J.A. et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039-1043 (2007).
98. Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786-792 (2005).
99. Epstein, J.I. et al. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am. J. Surg. Pathol. 38, 756-767 (2014).
100. Lai, S.L. et al. Molecular genetic characterization of neuroendocrine lung cancer cell lines. Anticancer Res. 15, 225-232 (1995).
101. Mertz, K.D. et al. Molecular characterization of TMPRSS2-ERG gene fusion in the NCI-H660 prostate cancer cell line: a new perspective for an old model. Neoplasia 9, 200-206 (2007).
102. Burchardt, T. et al. Transdifferentiation of prostate cancer cells to a neuroendocrine cell phenotype in vitro and in vivo. J. Urol. 162, 1800-1805 (1999).
103. Bang, Y.J. et al. Terminal neuroendocrine differentiation of human prostate carcinoma cells in response to increased intracellular cyclic AMP. Proc. Natl. Acad. Sci. USA 91, 5330-5334 (1994).
104. Qiu, Y., Robinson, D., Pretlow, T.G. & Kung, H.J. Etk/Bmx, a tyrosine kinase with a pleckstrin-homology domain, is an effector of phosphatidylinositol 3′-kinase and is involved in interleukin 6-induced neuroendocrine differentiation of prostate cancer cells. Proc. Natl. Acad. Sci. USA 95, 3644-3649 (1998).
105. Deng, X. et al. Ionizing radiation induces prostate cancer neuroendocrine differentiation through interplay of CREB and ATF2: implications for disease progression. Cancer Res. 68, 9663-9670 (2008).
106. Lin, D. et al. High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development. Cancer Res. 74, 1272-1283 (2014).
107. True, L.D. et al. A neuroendocrine/small cell prostate carcinoma xenograft-LuCaP 49. Am. J. Pathol. 161, 705-715 (2002).
108. van Haaften Day, C. et al. Xenografted small cell undifferentiated cancer of prostate: possible common origin with prostatic adenocarcinoma. Prostate 11, 271-279 (1987).
109. Pinthus, J.H. et al. WISH-PC2: a unique xenograft model of human prostatic small cell carcinoma. Cancer Res. 60, 6563-6567 (2000).
110. Lapuk, A.V. et al. From sequence to molecular pathology, and a mechanism driving the neuroendocrine phenotype in prostate cancer. J. Pathol. 227, 286-297 (2012).
111. Akamatsu, S. et al. The placental gene PEG10 promotes progression of neuroendocrine prostate cancer. Cell Reports 12, 922-936 (2015).
112. Aparicio, A. et al. Neuroendocrine prostate cancer xenografts with large-cell and small-cell features derived from a single patient's tumor: morphological, immunohistochemical, and gene expression profiles. Prostate 71, 846-856 (2011).
113. Noordzij, M.A. et al. Neuroendocrine differentiation in human prostatic tumor models. Am. J. Pathol. 149, 859-871 (1996).
114. Huss, W.J., Gregory, C.W. & Smith, G.J. Neuroendocrine cell differentiation in the CWR22 human prostate cancer xenograft: association with tumor cell proliferation prior to recurrence. Prostate 60, 91-97 (2004).
115. Chen, H. et al. Pathogenesis of prostatic small cell carcinoma involves the inactivation of the P53 pathway. Endocr. Relat. Cancer 19, 321-331 (2012).
116. Kareta, M.S. et al. Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis. Cell Stem Cell 16, 39-50 (2015).
117. Bishop, J.L. et al. The master neural transcription factor BRN2 is an androgen receptor-suppressed driver of neuroendocrine differentiation in prostate cancer. Cancer Discov. 7, 54-71 (2017).
118. Zou, M. et al. Transdifferentiation as a mechanism of treatment resistance in a mouse model of castration-resistant prostate cancer. Cancer Discov. http://dx.doi.org/10.1158/2159-8290.CD-16-1174 (2017).
119. Lynch, T.J. et al. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J. Clin. Oncol. 30, 2046-2054 (2012).
120. Nghiem, P.T. et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N. Engl. J. Med. 374, 2542-2552 (2016).
121. Khoo, K.H., Verma, C.S. & Lane, D.P. Drugging the p53 pathway: understanding the route to clinical efficacy. Nat. Rev. Drug Discov. 13, 217-236 (2014).
122. Mantovani, F., Walerych, D. & Sal, G.D. Targeting mutant p53 in cancer: a long road to precision therapy. FEBS J. 284, 837-850 (2017).
123. Brockmann, M. et al. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell 24, 75-89 (2013).
124. Gustafson, W.C. et al. Drugging MYCN through an allosteric transition in Aurora kinase A. Cancer Cell 26, 414-427 (2014).
125. Hook, K.E. et al. An integrated genomic approach to identify predictive biomarkers of response to the aurora kinase inhibitor PF-03814735. Mol. Cancer Ther. 11, 710-719 (2012).
126. Jahchan, N.S. et al. Identification and targeting of long-term tumor-propagating cells in small cell lung cancer. Cell Rep. 16, 644-656 (2016).
127. Baca, S.C. et al. Punctuated evolution of prostate cancer genomes. Cell 153, 666-677 (2013).
128. Bailey, P. et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531, 47-52 (2016).
129. Barbieri, C.E. et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat. Genet. 44, 685-689 (2012).
130. Biankin, A.V. et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 491, 399-405 (2012).
131. Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell 163, 1011-1025 (2015).
132. Grasso, C.S. et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature 487, 239-243 (2012).
133. Kumar, A. et al. Substantial interindividual and limited intraindividual genomic diversity among tumors from men with metastatic prostate cancer. Nat. Med. 22, 369-378 (2016).
134. Rudin, C.M. et al. Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer. Nat. Genet. 44, 1111-1116 (2012).
135. Taylor, B.S. et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 18, 11-22 (2010).
136. Marshall, G.M. et al. The prenatal origins of cancer. Nat. Rev. Cancer 14, 277-289 (2014).
137. Zimmerman, K.A. et al. Differential expression of myc family genes during murine development. Nature 319, 780-783 (1986).
138. Yuan, J. & Yankner, B.A. Apoptosis in the nervous system. Nature 407, 802-809 (2000).
139. Kelly, K. & Balk, S.P. Reprogramming to resist. Science 355, 29-30 (2017).