TY - JOUR
T1 - Clinical Benefit to an Aurora A Kinase Inhibitor in a Patient with Metastatic Integrase Interactor 1-Deficient Carcinoma
AU - Karantanos, Theodoros
AU - Rooper, Lisa
AU - Kang, Youme
AU - Lin, Cheng Ting
AU - Wenga, Pawla
AU - Sagorsky, Sarah
AU - Lauring, Josh
AU - Kang, Hyunseok
N1 - Publisher Copyright:
© AlphaMed Press 2018
PY - 2019/2
Y1 - 2019/2
N2 - Integrase interactor 1 (INI-1)-deficient carcinoma is a rare cancer characterized by the loss of the SWItch/Sucrose Non-Fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene (SMARCB1) and tends to follow an aggressive clinical course. There is no currently available standard therapy option, although a few promising treatment strategies, including enhancer of zeste homolog 2 (EZH2) inhibition, are under active investigation. This report describes a 30-year-old woman with INI-1-deficient carcinoma who progressed on combination chemotherapy and an EZH2 inhibitor. Next-generation-sequencing-based targeted cancer-related gene assay confirmed SMARCB1 loss and revealed other mutations in breast cancer 1 gene and checkpoint kinase 2 gene, which may have impacted her clinical course. After discussion at the molecular tumor board, she was offered alisertib, an aurora A kinase inhibitor, on a single-patient expanded-use program and achieved prolonged disease stabilization. Aurora A kinase inhibition may have an important role in the management of patients with INI-1-deficient tumors, warranting further evaluation in clinical studies. Key Points: Loss of the SWItch/Sucrose Non-Fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene (SMARCB1), which encodes integrase interactor 1 (INI-1), is associated with various mesenchymal malignancies, but a few carcinomas with rhabdoid features have been recently described as a distinct entity. INI-1-deficient carcinoma can be very aggressive, and there is no known treatment option available. There are encouraging preliminary data with an enhancer of zeste homolog 2 inhibitor, tazematostat, in INI-1-deficient malignancies, including INI-1-deficient carcinomas. Loss of INI-1 can activate aurora A kinase (AurkA), and inhibition of AurkA by alisertib could be a viable option and warrants further investigation in this cancer. Clinical genomic profiling can confirm diagnosis of molecularly defined malignancy and provide insights on therapeutic options.
AB - Integrase interactor 1 (INI-1)-deficient carcinoma is a rare cancer characterized by the loss of the SWItch/Sucrose Non-Fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene (SMARCB1) and tends to follow an aggressive clinical course. There is no currently available standard therapy option, although a few promising treatment strategies, including enhancer of zeste homolog 2 (EZH2) inhibition, are under active investigation. This report describes a 30-year-old woman with INI-1-deficient carcinoma who progressed on combination chemotherapy and an EZH2 inhibitor. Next-generation-sequencing-based targeted cancer-related gene assay confirmed SMARCB1 loss and revealed other mutations in breast cancer 1 gene and checkpoint kinase 2 gene, which may have impacted her clinical course. After discussion at the molecular tumor board, she was offered alisertib, an aurora A kinase inhibitor, on a single-patient expanded-use program and achieved prolonged disease stabilization. Aurora A kinase inhibition may have an important role in the management of patients with INI-1-deficient tumors, warranting further evaluation in clinical studies. Key Points: Loss of the SWItch/Sucrose Non-Fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 gene (SMARCB1), which encodes integrase interactor 1 (INI-1), is associated with various mesenchymal malignancies, but a few carcinomas with rhabdoid features have been recently described as a distinct entity. INI-1-deficient carcinoma can be very aggressive, and there is no known treatment option available. There are encouraging preliminary data with an enhancer of zeste homolog 2 inhibitor, tazematostat, in INI-1-deficient malignancies, including INI-1-deficient carcinomas. Loss of INI-1 can activate aurora A kinase (AurkA), and inhibition of AurkA by alisertib could be a viable option and warrants further investigation in this cancer. Clinical genomic profiling can confirm diagnosis of molecularly defined malignancy and provide insights on therapeutic options.
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U2 - 10.1634/theoncologist.2018-0279
DO - 10.1634/theoncologist.2018-0279
M3 - Article
C2 - 30297384
AN - SCOPUS:85054576516
SN - 1083-7159
VL - 24
SP - 146
EP - 150
JO - Oncologist
JF - Oncologist
IS - 2
ER -