Genomics driven precision oncology in advanced biliary tract cancer improves survival.
Genomics driven precision oncology in advanced biliary tract cancer improves survival.
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DOI：
10.1016/j.neo.2023.100910
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发表时间：
2023-08
期刊：
影响因子：
4.8
通讯作者：
Sahai, Vaibhav
中科院分区：
文献类型：
--
作者：
Kumar-Sinha, Chandan;Vats, Pankaj;Tran, Nguyen;Robinson, Dan R.;Gunchick, Valerie;Wu, Yi-Mi;Cao, Xuhong;Ning, Yu;Wang, Rui;Rabban, Erica;Bell, Janice;Shankar, Sunita;Mannan, Rahul;Zhang, Yuping;Zalupski, Mark M.;Chinnaiyan, Arul M.;Sahai, Vaibhav
Biliary tract cancers (BTCs), including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer are rare but aggressive malignancies with few effective therapies. Integrative clinical sequencing of 124 BTC patients at University of Michigan identified actionable/ potentially actionable aberrations in a majority of cases. Patients treated with molecularly matched targeted therapies showed a significantly improved survival as compared to those who could not be treated with matched therapy. Biliary tract cancers (BTCs) including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are rare but aggressive malignancies with few effective standard of care therapies. We implemented integrative clinical sequencing of advanced BTC tumors from 124 consecutive patients who progressed on standard therapies (N=92 with MI-ONCOSEQ and N=32 with commercial gene panels) enrolled between 2011-2020. Genomic profiling of paired tumor and normal DNA and tumor transcriptome (RNA) sequencing identified actionable somatic and germline genomic alterations in 54 patients (43.5%), and potentially actionable alterations in 79 (63.7%) of the cohort. Of these, patients who received matched targeted therapy (22; 40.7%) had a median overall survival of 28.1 months compared to 13.3 months in those who did not receive matched targeted therapy (32; P < 0.01), or 13.9 months in those without actionable mutations (70; P < 0.01). Additionally, we discovered recurrent activating mutations in FGFR2, and a novel association between KRAS and BRAF mutant tumors with high expression of immune modulatory protein NT5E (CD73) that may represent novel therapeutic avenues. Overall, the identification of actionable/ potentially actionable aberrations in a large proportion of cases, and improvement in survival with precision oncology supports molecular analysis and clinical sequencing for all patients with advanced BTC.
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影响因子：
8.8
作者：
Farshidfar F;Zheng S;Gingras MC;Newton Y;Shih J;Robertson AG;Hinoue T;Hoadley KA;Gibb EA;Roszik J;Covington KR;Wu CC;Shinbrot E;Stransky N;Hegde A;Yang JD;Reznik E;Sadeghi S;Pedamallu CS;Ojesina AI;Hess JM;Auman JT;Rhie SK;Bowlby R;Borad MJ;Cancer Genome Atlas Network;Zhu AX;Stuart JM;Sander C;Akbani R;Cherniack AD;Deshpande V;Mounajjed T;Foo WC;Torbenson MS;Kleiner DE;Laird PW;Wheeler DA;McRee AJ;Bathe OF;Andersen JB;Bardeesy N;Roberts LR;Kwong LN
通讯作者：
Kwong LN
DOI：
10.1016/s1470-2045(20)30157-1
发表时间：
2020-06
期刊：
The Lancet. Oncology
影响因子：
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作者：
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通讯作者：
Zhu AX
DOI：
10.1158/1078-0432.ccr-13-1746
发表时间：
2013-12-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Hutchinson KE;Lipson D;Stephens PJ;Otto G;Lehmann BD;Lyle PL;Vnencak-Jones CL;Ross JS;Pietenpol JA;Sosman JA;Puzanov I;Miller VA;Pao W
通讯作者：
Pao W
影响因子：
28.5
作者：
Javle M;Churi C;Kang HC;Shroff R;Janku F;Surapaneni R;Zuo M;Barrera C;Alshamsi H;Krishnan S;Mishra L;Wolff RA;Kaseb AO;Thomas MB;Siegel AB
通讯作者：
Siegel AB
DOI：
10.1016/s1470-2045(20)30109-1
发表时间：
2020-05
期刊：
The Lancet. Oncology
影响因子：
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作者：
Abou-Alfa GK;Sahai V;Hollebecque A;Vaccaro G;Melisi D;Al-Rajabi R;Paulson AS;Borad MJ;Gallinson D;Murphy AG;Oh DY;Dotan E;Catenacci DV;Van Cutsem E;Ji T;Lihou CF;Zhen H;Féliz L;Vogel A
通讯作者：
Vogel A