Literature DB >> 33199493

Regulation of CEACAM5 and Therapeutic Efficacy of an Anti-CEACAM5-SN38 Antibody-drug Conjugate in Neuroendocrine Prostate Cancer.

Diana C DeLucia1, Thomas M Cardillo2, Lisa Ang1, Mark P Labrecque3, Ailin Zhang1, James E Hopkins1, Navonil De Sarkar1, Ilsa Coleman1, Rui M Gil da Costa1,4, Eva Corey3, Lawrence D True5, Michael C Haffner1,4,5, Michael T Schweizer4,6, Colm Morrissey3, Peter S Nelson1,3,4,5,6, John K Lee7,4,5,6.   

Abstract

PURPOSE: Neuroendocrine prostate cancer (NEPC) is an aggressive form of castration-resistant prostate cancer (CRPC) for which effective therapies are lacking. We previously identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a promising NEPC cell surface antigen. Here we investigated the scope of CEACAM5 expression in end-stage prostate cancer, the basis for CEACAM5 enrichment in NEPC, and the therapeutic potential of the CEACAM5 antibody-drug conjugate labetuzumab govitecan in prostate cancer. EXPERIMENTAL
DESIGN: The expression of CEACAM5 and other clinically relevant antigens was characterized by multiplex immunofluorescence of a tissue microarray comprising metastatic tumors from 34 lethal metastatic CRPC (mCRPC) cases. A genetically defined neuroendocrine transdifferentiation assay of prostate cancer was developed to evaluate mechanisms of CEACAM5 regulation in NEPC. The specificity and efficacy of labetuzumab govitecan was determined in CEACAM5+ prostate cancer cell lines and patient-derived xenografts models.
RESULTS: CEACAM5 expression was enriched in NEPC compared with other mCRPC subtypes and minimally overlapped with prostate-specific membrane antigen, prostate stem cell antigen, and trophoblast cell surface antigen 2 expression. We focused on a correlation between the expression of the pioneer transcription factor ASCL1 and CEACAM5 to determine that ASCL1 can drive neuroendocrine reprogramming of prostate cancer which is associated with increased chromatin accessibility of the CEACAM5 core promoter and CEACAM5 expression. Labetuzumab govitecan induced DNA damage in CEACAM5+ prostate cancer cell lines and marked antitumor responses in CEACAM5+ CRPC xenograft models including chemotherapy-resistant NEPC.
CONCLUSIONS: Our findings provide insights into the scope and regulation of CEACAM5 expression in prostate cancer and strong support for clinical studies of labetuzumab govitecan for NEPC. ©2020 American Association for Cancer Research.

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Year:  2020        PMID： 33199493      PMCID： PMC7854497          DOI： 10.1158/1078-0432.CCR-20-3396

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN： 1078-0432            Impact factor:   13.801


  56 in total

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Authors:  Charles M Rudin; John T Poirier; Lauren Averett Byers; Caroline Dive; Afshin Dowlati; Julie George; John V Heymach; Jane E Johnson; Jonathan M Lehman; David MacPherson; Pierre P Massion; John D Minna; Trudy G Oliver; Vito Quaranta; Julien Sage; Roman K Thomas; Christopher R Vakoc; Adi F Gazdar
Journal:  Nat Rev Cancer       Date:  2019-05       Impact factor: 60.716

2.  ATAC Primer Tool for targeted analysis of accessible chromatin.

Authors:  Kathryn E Yost; Ava C Carter; Jin Xu; Ulrike Litzenburger; Howard Y Chang
Journal:  Nat Methods       Date:  2018-04-27       Impact factor: 28.547

3.  Identification of Therapeutic Vulnerabilities in Small-cell Neuroendocrine Prostate Cancer.

Authors:  Alexandra N Corella; Ma Victoria Andrea Cabiliza Ordonio; Ilsa Coleman; Jared M Lucas; Arja Kaipainen; Holly M Nguyen; Daniel Sondheim; Lisha G Brown; Lawrence D True; John K Lee; David MacPherson; Paul Nghiem; Roman Gulati; Colm Morrissey; Eva Corey; Peter S Nelson
Journal:  Clin Cancer Res       Date:  2019-12-05       Impact factor: 12.531

4.  Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.

Authors:  G L Wright; B M Grob; C Haley; K Grossman; K Newhall; D Petrylak; J Troyer; A Konchuba; P F Schellhammer; R Moriarty
Journal:  Urology       Date:  1996-08       Impact factor: 2.649

5.  Relationship of tissue carcinoembryonic antigen and calcitonin to tumor virulence in medullary thyroid carcinoma. An immunohistochemical study in early, localized, and virulent disseminated stages of disease.

Authors:  G Mendelsohn; S A Wells; S B Baylin
Journal:  Cancer       Date:  1984-08-15       Impact factor: 6.860

6.  Preclinical Activity of Sacituzumab Govitecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2 (Trop-2) Linked to the Active Metabolite of Irinotecan (SN-38), in Ovarian Cancer.

Authors:  Emanuele Perrone; Salvatore Lopez; Burak Zeybek; Stefania Bellone; Elena Bonazzoli; Silvia Pelligra; Luca Zammataro; Aranzazu Manzano; Paola Manara; Anna Bianchi; Natalia Buza; Joan Tymon-Rosario; Gary Altwerger; Chanhee Han; Gulden Menderes; Elena Ratner; Dan-Arin Silasi; Masoud Azodi; Pei Hui; Peter E Schwartz; Giovanni Scambia; Alessandro D Santin
Journal:  Front Oncol       Date:  2020-02-12       Impact factor: 6.244

7.  An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: III. Expressions of EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63 in normal mucosa and in 42 cases.

Authors:  Tadashi Terada
Journal:  Int J Clin Exp Pathol       Date:  2013-03-15

8.  Expression patterns of CEACAM5 and CEACAM6 in primary and metastatic cancers.

Authors:  Rosalyn D Blumenthal; Evelyn Leon; Hans J Hansen; David M Goldenberg
Journal:  BMC Cancer       Date:  2007-01-03       Impact factor: 4.430

9.  POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer.

Authors:  Yu-Han Huang; Olaf Klingbeil; Xue-Yan He; Xiaoli S Wu; Gayatri Arun; Bin Lu; Tim D D Somerville; Joseph P Milazzo; John E Wilkinson; Osama E Demerdash; David L Spector; Mikala Egeblad; Junwei Shi; Christopher R Vakoc
Journal:  Genes Dev       Date:  2018-06-26       Impact factor: 12.890

10.  Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development.

Authors:  Xindong Liu; Xin Chen; Bo Zhong; Aibo Wang; Xiaohu Wang; Fuliang Chu; Roza I Nurieva; Xiaowei Yan; Ping Chen; Laurens G van der Flier; Hiroko Nakatsukasa; Sattva S Neelapu; Wanjun Chen; Hans Clevers; Qiang Tian; Hai Qi; Lai Wei; Chen Dong
Journal:  Nature       Date:  2014-01-19       Impact factor: 49.962
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  10 in total

1.  Development of Cancer Immunotherapies.

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Journal:  Cancer Treat Res       Date:  2022

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Review 3.  The heterogeneity of prostate cancers lacking AR activity will require diverse treatment approaches.

Authors:  Mark P Labrecque; Joshi J Alumkal; Ilsa M Coleman; Peter S Nelson; Colm Morrissey
Journal:  Endocr Relat Cancer       Date:  2021-07-15       Impact factor: 5.900

4.  Subtype heterogeneity and epigenetic convergence in neuroendocrine prostate cancer.

Authors:  Paloma Cejas; Yingtian Xie; Alba Font-Tello; Klothilda Lim; Sudeepa Syamala; Xintao Qiu; Alok K Tewari; Neel Shah; Holly M Nguyen; Radhika A Patel; Lisha Brown; Ilsa Coleman; Wenzel M Hackeng; Lodewijk Brosens; Koen M A Dreijerink; Leigh Ellis; Sarah Abou Alaiwi; Ji-Heui Seo; Sylvan Baca; Himisha Beltran; Francesca Khani; Mark Pomerantz; Alessandra Dall'Agnese; Jett Crowdis; Eliezer M Van Allen; Joaquim Bellmunt; Colm Morrisey; Peter S Nelson; James DeCaprio; Anna Farago; Nicholas Dyson; Benjamin Drapkin; X Shirley Liu; Matthew Freedman; Michael C Haffner; Eva Corey; Myles Brown; Henry W Long
Journal:  Nat Commun       Date:  2021-10-01       Impact factor: 17.694

Review 5.  The Potential of Topoisomerase Inhibitor-Based Antibody-Drug Conjugates.

Authors:  Seungmin Han; Kwang Suk Lim; Brody J Blackburn; Jina Yun; Charles W Putnam; David A Bull; Young-Wook Won
Journal:  Pharmaceutics       Date:  2022-08-16       Impact factor: 6.525

6.  Case Report: 18F-PSMA PET/CT Scan in Castration Resistant Prostate Cancer With Aggressive Neuroendocrine Differentiation.

Authors:  Marco Bergamini; Alberto Dalla Volta; Irene Caramella; Luisa Bercich; Simona Fisogni; Mattia Bertoli; Francesca Valcamonico; Salvatore Grisanti; Pietro Luigi Poliani; Francesco Bertagna; Alfredo Berruti
Journal:  Front Oncol       Date:  2022-07-22       Impact factor: 5.738

7.  RNA Splicing Factors SRRM3 and SRRM4 Distinguish Molecular Phenotypes of Castration-Resistant Neuroendocrine Prostate Cancer.

Authors:  Mark P Labrecque; Lisha G Brown; Ilsa M Coleman; Bryce Lakely; Nicholas J Brady; John K Lee; Holly M Nguyen; Dapei Li; Brian Hanratty; Michael C Haffner; David S Rickman; Lawrence D True; Daniel W Lin; Hung-Ming Lam; Joshi J Alumkal; Eva Corey; Peter S Nelson; Colm Morrissey
Journal:  Cancer Res       Date:  2021-07-26       Impact factor: 12.701

8.  Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model.

Authors:  Molykutty J Aryankalayil; Shannon Martello; Michelle A Bylicky; Sunita Chopra; Jared M May; Aman Shankardass; Laurel MacMillan; Landy Sun; Jaleal Sanjak; Claire Vanpouille-Box; Iris Eke; C Norman Coleman
Journal:  J Transl Med       Date:  2021-08-07       Impact factor: 5.531

Review 9.  Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs.

Authors:  Eva Slabáková; Zuzana Kahounová; Jiřina Procházková; Karel Souček
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Review 10.  Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation.

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  10 in total

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