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Mouse-human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck

 Hye Ryun Kim  ;  Han Na Kang  ;  Mi Ran Yun  ;  Kwon Young Ju  ;  Jae Woo Choi  ;  Dong Min Jung  ;  Kyoung Ho Pyo  ;  Min Hee Hong  ;  Myoung-Ju Ahn  ;  Jong-Mu Sun  ;  Han Sang Kim  ;  Jinna Kim  ;  Jinseon Yoo  ;  Kyu Ryung Kim  ;  Yoon Woo Koh  ;  Se Heon Kim  ;  Eun Chang Choi  ;  Sun Ock Yoon  ;  Hyo Sup Shim  ;  Soonmyung Paik  ;  Tae-Min Kim  ;  Byoung Chul Cho 
 BRITISH JOURNAL OF CANCER, Vol.123(12) : 1720-1729, 2020-12 
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Background: Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs).

Methods: Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab.

Results: For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone.

Conclusions: The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN.

Clinical trial registration: NCT01527877.
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Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
Yonsei Authors
Koh, Yoon Woo(고윤우)
Kim, Se Heon(김세헌)
Kim, Jinna(김진아) ORCID logo https://orcid.org/0000-0002-9978-4356
Kim, Han Sang(김한상) ORCID logo https://orcid.org/0000-0002-6504-9927
Kim, Hye Ryun(김혜련) ORCID logo https://orcid.org/0000-0002-1842-9070
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
Cho, Byoung Chul(조병철) ORCID logo https://orcid.org/0000-0002-5562-270X
Choi, Eun Chang(최은창)
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
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