Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib

Publication Date:
2018-06-16
Publisher:
The American Association for Cancer Research (AACR)
Print ISSN:
1078-0432
Electronic ISSN:
1557-3265
Topics:
Medicine
Published by:
http://www.aacr.org/
_version_ 1836398973046226944
autor Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
beschreibung Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase ( ALK ) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C–activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA). Prostate cancer databases were queried for alterations in ALK gene, mRNA, and its impact in clinical outcomes. In vitro prostate cell line/organoid models were generated by lentiviral-mediated expression of ALK and ALK F1174C and assessed for response to ALK inhibitors crizotinib and alectinib. Results: NGS analysis of the primary tumor and ctDNA of a 39-year-old patient with refractory SSCP identified ALK F1174C mutation. Treatment with second-generation ALK inhibitor alectinib resulted in radiographic stable disease for over 6 months, symptomatic improvement, and significant molecular response as reflected by declining ctDNA allele fraction. Analysis of prostate cancer datasets showed that ALK amplification was associated with poor outcome. In prostate cancer cells and organoids, ALK F1174C expression enhanced growth and induced expression of the neuroendocrine marker neuron-specific enolase. Alectinib was more effective than crizotinib in inhibiting ALK F1174C–expressing cell growth. Conclusions: These findings implicate ALK -activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting ALK molecular alterations in some patients with SCCP. Clin Cancer Res; 24(12); 2732–9. ©2018 AACR .
citation_standardnr 6284465
datenlieferant ipn_articles
feed_id 9363
feed_publisher The American Association for Cancer Research (AACR)
feed_publisher_url http://www.aacr.org/
insertion_date 2018-06-16
journaleissn 1557-3265
journalissn 1078-0432
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher The American Association for Cancer Research (AACR)
quelle Clinical Cancer Research
relation http://clincancerres.aacrjournals.org/cgi/content/short/24/12/2732?rss=1
search_space articles
shingle_author_1 Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
shingle_author_2 Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
shingle_author_3 Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
shingle_author_4 Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
shingle_catch_all_1 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase ( ALK ) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C–activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA). Prostate cancer databases were queried for alterations in ALK gene, mRNA, and its impact in clinical outcomes. In vitro prostate cell line/organoid models were generated by lentiviral-mediated expression of ALK and ALK F1174C and assessed for response to ALK inhibitors crizotinib and alectinib. Results: NGS analysis of the primary tumor and ctDNA of a 39-year-old patient with refractory SSCP identified ALK F1174C mutation. Treatment with second-generation ALK inhibitor alectinib resulted in radiographic stable disease for over 6 months, symptomatic improvement, and significant molecular response as reflected by declining ctDNA allele fraction. Analysis of prostate cancer datasets showed that ALK amplification was associated with poor outcome. In prostate cancer cells and organoids, ALK F1174C expression enhanced growth and induced expression of the neuroendocrine marker neuron-specific enolase. Alectinib was more effective than crizotinib in inhibiting ALK F1174C–expressing cell growth. Conclusions: These findings implicate ALK -activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting ALK molecular alterations in some patients with SCCP. Clin Cancer Res; 24(12); 2732–9. ©2018 AACR .
Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_2 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase ( ALK ) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C–activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA). Prostate cancer databases were queried for alterations in ALK gene, mRNA, and its impact in clinical outcomes. In vitro prostate cell line/organoid models were generated by lentiviral-mediated expression of ALK and ALK F1174C and assessed for response to ALK inhibitors crizotinib and alectinib. Results: NGS analysis of the primary tumor and ctDNA of a 39-year-old patient with refractory SSCP identified ALK F1174C mutation. Treatment with second-generation ALK inhibitor alectinib resulted in radiographic stable disease for over 6 months, symptomatic improvement, and significant molecular response as reflected by declining ctDNA allele fraction. Analysis of prostate cancer datasets showed that ALK amplification was associated with poor outcome. In prostate cancer cells and organoids, ALK F1174C expression enhanced growth and induced expression of the neuroendocrine marker neuron-specific enolase. Alectinib was more effective than crizotinib in inhibiting ALK F1174C–expressing cell growth. Conclusions: These findings implicate ALK -activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting ALK molecular alterations in some patients with SCCP. Clin Cancer Res; 24(12); 2732–9. ©2018 AACR .
Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_3 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase ( ALK ) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C–activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA). Prostate cancer databases were queried for alterations in ALK gene, mRNA, and its impact in clinical outcomes. In vitro prostate cell line/organoid models were generated by lentiviral-mediated expression of ALK and ALK F1174C and assessed for response to ALK inhibitors crizotinib and alectinib. Results: NGS analysis of the primary tumor and ctDNA of a 39-year-old patient with refractory SSCP identified ALK F1174C mutation. Treatment with second-generation ALK inhibitor alectinib resulted in radiographic stable disease for over 6 months, symptomatic improvement, and significant molecular response as reflected by declining ctDNA allele fraction. Analysis of prostate cancer datasets showed that ALK amplification was associated with poor outcome. In prostate cancer cells and organoids, ALK F1174C expression enhanced growth and induced expression of the neuroendocrine marker neuron-specific enolase. Alectinib was more effective than crizotinib in inhibiting ALK F1174C–expressing cell growth. Conclusions: These findings implicate ALK -activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting ALK molecular alterations in some patients with SCCP. Clin Cancer Res; 24(12); 2732–9. ©2018 AACR .
Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_catch_all_4 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
Purpose: Small cell carcinoma of the prostate (SCCP) is an aggressive disease that can arise de novo or by transdifferentiation from prostate adenocarcinoma. Alterations in anaplastic lymphoma kinase ( ALK ) gene are involved in neuroblastoma, lung cancer, and other malignancies, but its role in SCCP has not been documented. We describe a patient with refractory de novo SCCP with ALK F1174C–activating mutation who obtained clinical benefit from treatment with ALK inhibitor. Experimental Design: Next-generation sequencing (NGS) was used to analyze primary and circulating tumor DNA (ctDNA). Prostate cancer databases were queried for alterations in ALK gene, mRNA, and its impact in clinical outcomes. In vitro prostate cell line/organoid models were generated by lentiviral-mediated expression of ALK and ALK F1174C and assessed for response to ALK inhibitors crizotinib and alectinib. Results: NGS analysis of the primary tumor and ctDNA of a 39-year-old patient with refractory SSCP identified ALK F1174C mutation. Treatment with second-generation ALK inhibitor alectinib resulted in radiographic stable disease for over 6 months, symptomatic improvement, and significant molecular response as reflected by declining ctDNA allele fraction. Analysis of prostate cancer datasets showed that ALK amplification was associated with poor outcome. In prostate cancer cells and organoids, ALK F1174C expression enhanced growth and induced expression of the neuroendocrine marker neuron-specific enolase. Alectinib was more effective than crizotinib in inhibiting ALK F1174C–expressing cell growth. Conclusions: These findings implicate ALK -activating mutations in SCCP pathogenesis and suggest the therapeutic potential of targeting ALK molecular alterations in some patients with SCCP. Clin Cancer Res; 24(12); 2732–9. ©2018 AACR .
Carneiro, B. A., Pamarthy, S., Shah, A. N., Sagar, V., Unno, K., Han, H., Yang, X. J., Costa, R. B., Nagy, R. J., Lanman, R. B., Kuzel, T. M., Ross, J. S., Gay, L., Elvin, J. A., Ali, S. M., Cristofanilli, M., Chae, Y. K., Giles, F. J., Abdulkadir, S. A.
The American Association for Cancer Research (AACR)
1078-0432
10780432
1557-3265
15573265
shingle_title_1 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
shingle_title_2 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
shingle_title_3 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
shingle_title_4 Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
timestamp 2025-06-30T23:35:35.060Z
titel Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
titel_suche Anaplastic Lymphoma Kinase Mutation (ALK F1174C) in Small Cell Carcinoma of the Prostate and Molecular Response to Alectinib
topic WW-YZ
uid ipn_articles_6284465