The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients

被引：292

作者：

Zill, Oliver A. ^{[1
]}

Banks, Kimberly C. ^{[1
]}

Fairclough, Stephen R. ^{[1
]}

Mortimer, Stefanie A. ^{[1
]}

Vowles, James V. ^{[1
]}

Mokhtari, Reza ^{[1
]}

Gandara, David R. ^{[2
]}

Mack, Philip C. ^{[2
]}

Odegaard, Justin I. ^{[1
]}

Nagy, Rebecca J. ^{[1
]}

Baca, Arthur M. ^{[1
]}

Eltoukhy, Helmy ^{[1
]}

Chudova, Darya I. ^{[1
]}

Lanman, Richard B. ^{[1
]}

Talasaz, AmirAli ^{[1
]}

机构：

[1] Guardant Hlth Inc, 505 Penobscot Dr, Redwood City, CA 94063 USA

[2] Univ Calif Davis, Ctr Comprehens Canc, Sacramento, CA 95817 USA

来源：

CLINICAL CANCER RESEARCH | 2018年 / 24卷 / 15期

关键词：

LUNG-CANCER; COLORECTAL-CANCER; BREAST-CANCER; MUTATION; EGFR; HETEROGENEITY; EVOLUTION; RESISTANCE; THERAPY; METASTASIS;

D O I：

10.1158/1078-0432.CCR-17-3837

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: Cell-free DNA (cfDNA) sequencing provides a noninvasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types. To facilitate interpretation of the genomic complexity of circulating tumor DNA in advanced, treated cancer patients, we developed methods to identify cfDNA copy-number driver alterations and cfDNA clonality. Results: Patterns and prevalence of cfDNA alterations in major driver genes for non-small cell lung, breast, and colorectal cancer largely recapitulated those from tumor tissue sequencing compendia (The Cancer Genome Atlas and COSMIC; r = 0.90-0.99), with the principal differences in alteration prevalence being due to patient treatment. This highly sensitive cfDNA sequencing assay revealed numerous subclonal tumor-derived alterations, expected as a result of clonal evolution, but leading to an apparent departure from mutual exclusivity in treatment-naive tumors. Upon applying novel cfDNA clonality and copy-number driver identification methods, robust mutual exclusivity was observed among predicted truncal driver cfDNA alterations (FDR = 5 x 10(-7) for EGFR and ERBB2), in effect distinguishing tumor-initiating alterations from secondary alterations. Treatment-associated resistance, including both novel alterations and parallel evolution, was common in the cfDNA cohort and was enriched in patients with targetable driver alterations (>18.6% patients). Conclusions: Together, these retrospective analyses of a large cfDNA sequencing data set reveal subclonal structures and emerging resistance in advanced solid tumors. (C) 2018 AACR.

引用

页码：3528 / 3538

页数：11

共 37 条

[1] Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution [J].

Abbosh, Christopher ;

Birkbak, Nicolai J. ;

Wilson, Gareth A. ;

Jamal-Hanjani, Mariam ;

Constantin, Tudor ;

Salari, Raheleh ;

Le Quesne, John ;

Moore, David A. ;

Veeriah, Selvaraju ;

Rosenthal, Rachel ;

Marafioti, Teresa ;

Kirkizlar, Eser ;

Watkins, Thomas B. K. ;

McGranahan, Nicholas ;

Ward, Sophia ;

Martinson, Luke ;

Riley, Joan ;

Fraioli, Francesco ;

Al Bakir, Maise ;

Gronroos, Eva ;

Zambrana, Francisco ;

Endozo, Raymondo ;

Bi, Wenya Linda ;

Fennessy, Fiona M. ;

Sponer, Nicole ;

Johnson, Diana ;

Laycock, Joanne ;

Shafi, Seema ;

Czyzewska-Khan, Justyna ;

Rowan, Andrew ;

Chambers, Tim ;

Matthews, Nik ;

Turajlic, Samra ;

Hiley, Crispin ;

Lee, Siow Ming ;

Forster, Martin D. ;

Ahmad, Tanya ;

Falzon, Mary ;

Borg, Elaine ;

Lawrence, David ;

Hayward, Martin ;

Kolvekar, Shyam ;

Panagiotopoulos, Nikolaos ;

Janes, Sam M. ;

Thakrar, Ricky ;

Ahmed, Asia ;

Blackhall, Fiona ;

Summers, Yvonne ;

Hafez, Dina ;

Naik, Ashwini .

NATURE, 2017, 545 (7655) :446-+

[2] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[3] AACR Project GENIE: Powering Precision Medicine through an International Consortium [J].

Andre, Fabrice ;

Arnedos, Monica ;

Baras, Alexander S. ;

Baselga, Jose ;

Bedard, Philippe L. ;

Berger, Michael F. ;

Bierkens, Mariska ;

Calvo, Fabien ;

Cerami, Ethan ;

Chakravarty, Debyani ;

Dang, Kristen K. ;

Davidson, Nancy E. ;

Del Vecchio, Fitz Catherine ;

Dogan, Semih ;

DuBois, Raymond N. ;

Ducar, Matthew D. ;

Futreal, P. Andrew ;

Gao Jianjiong ;

Garcia, Francisco ;

Gardos, Stu ;

Gocke, Christopher D. ;

Gross, Benjamin E. ;

Guinney, Justin ;

Heins, Zachary J. ;

Hintzen, Stephanie ;

Horlings, Hugo ;

Hudecek, Jan ;

Hyman, David M. ;

Kamel-Reid, Suzanne ;

Kandoth, Cyriac ;

Kinyua, Walter ;

Kumari, Priti ;

Kundra, Ritika ;

Ladanyi, Marc ;

Lefebvre, Celine ;

LeNoue-Newton, Michele L. ;

Lepisto, Eva M. ;

Levy, Mia A. ;

Lindeman, Neal, I ;

Lindsay, James ;

Liu, David ;

Lu Zhibin ;

MacConaill, Laura E. ;

Ian, Maurer ;

Maxwell, David S. ;

Meijer, Gerrit A. ;

Meric-Bernstam, Funda ;

Micheel, Christine M. ;

Miller, Clinton ;

Mills, Gordon .

CANCER DISCOVERY, 2017, 7 (08) :818-831

[4] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[5] Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer [J].

Gainor, Justin F. ;

Dardaei, Leila ;

Yoda, Satoshi ;

Friboulet, Luc ;

Leshchiner, Ignaty ;

Katayama, Ryohei ;

Dagogo-Jack, Ibiayi ;

Gadgeel, Shirish ;

Schultz, Katherine ;

Singh, Manrose ;

Chin, Emily ;

Parks, Melissa ;

Lee, Dana ;

DiCecca, Richard H. ;

Lockerman, Elizabeth ;

Huynh, Tiffany ;

Logan, Jennifer ;

Ritterhouse, Lauren L. ;

Le, Long P. ;

Muniappan, Ashok ;

Digumarthy, Subba ;

Channick, Colleen ;

Keyes, Colleen ;

Getz, Gad ;

Dias-Santagata, Dora ;

Heist, Rebecca S. ;

Lennerz, Jochen ;

Sequist, Lecia V. ;

Benes, Cyril H. ;

Iafrate, A. John ;

Mino-Kenudson, Mari ;

Engelman, Jeffrey A. ;

Shaw, Alice T. .

CANCER DISCOVERY, 2016, 6 (10) :1118-1133

[6] Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing [J].

Gerlinger, Marco ;

Rowan, Andrew J. ;

Horswell, Stuart ;

Larkin, James ;

Endesfelder, David ;

Gronroos, Eva ;

Martinez, Pierre ;

Matthews, Nicholas ;

Stewart, Aengus ;

Tarpey, Patrick ;

Varela, Ignacio ;

Phillimore, Benjamin ;

Begum, Sharmin ;

McDonald, Neil Q. ;

Butler, Adam ;

Jones, David ;

Raine, Keiran ;

Latimer, Calli ;

Santos, Claudio R. ;

Nohadani, Mahrokh ;

Eklund, Aron C. ;

Spencer-Dene, Bradley ;

Clark, Graham ;

Pickering, Lisa ;

Stamp, Gordon ;

Gore, Martin ;

Szallasi, Zoltan ;

Downward, Julian ;

Futreal, P. Andrew ;

Swanton, Charles .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (10) :883-892

[7] Attack of the clones [J].

Govindan, Ramaswamy .

SCIENCE, 2014, 346 (6206) :169-170

[8]

Goyal L, 2017, CANCER DISCOV, V7, P1

[9] Distinct subclonal tumour responses to therapy revealed by circulating cell-free DNA [J].

Gremel, G. ;

Lee, R. J. ;

Girotti, M. R. ;

Mandal, A. K. ;

Valpione, S. ;

Garner, G. ;

Ayub, M. ;

Wood, S. ;

Rothwell, D. G. ;

Fusi, A. ;

Wallace, A. ;

Brady, G. ;

Dive, C. ;

Dhomen, N. ;

Lorigan, P. ;

Marais, R. .

ANNALS OF ONCOLOGY, 2016, 27 (10) :1959-1965

[10] Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium [J].

Grossman, R. L. ;

Abel, B. ;

Angiuoli, S. ;

Barrett, J. C. ;

Bassett, D. ;

Bramlett, K. ;

Blumenthal, G. M. ;

Carlsson, A. ;

Cortese, R. ;

DiGiovanna, J. ;

Davis-Dusenbery, B. ;

Dittamore, R. ;

Eberhard, D. A. ;

Febbo, P. ;

Fitzsimons, M. ;

Flamig, Z. ;

Godsey, J. ;

Goswami, J. ;

Gruen, A. ;

Ortuno, F. ;

Han, J. ;

Hayes, D. ;

Hicks, J. ;

Holloway, D. ;

Hovelson, D. ;

Johnson, J. ;

Juhl, H. ;

Kalamegham, R. ;

Kamal, R. ;

Kang, Q. ;

Kelloff, G. J. ;

Klozenbuecher, M. ;

Kolatkar, A. ;

Kuhn, P. ;

Langone, K. ;

Leary, R. ;

Loverso, P. ;

Manmathan, H. ;

Martin, A-M ;

Martini, J. ;

Miller, D. ;

Mitchell, M. ;

Morgan, T. ;

Mulpuri, R. ;

Nguyen, T. ;

Otto, G. ;

Pathak, A. ;

Peters, E. ;

Philip, R. ;

Posadas, E. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2017, 101 (05) :589-592

← 1 2 3 4 →

共 37 条

[1] Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution [J].

Abbosh, Christopher ;

Birkbak, Nicolai J. ;

Wilson, Gareth A. ;

Jamal-Hanjani, Mariam ;

Constantin, Tudor ;

Salari, Raheleh ;

Le Quesne, John ;

Moore, David A. ;

Veeriah, Selvaraju ;

Rosenthal, Rachel ;

Marafioti, Teresa ;

Kirkizlar, Eser ;

Watkins, Thomas B. K. ;

McGranahan, Nicholas ;

Ward, Sophia ;

Martinson, Luke ;

Riley, Joan ;

Fraioli, Francesco ;

Al Bakir, Maise ;

Gronroos, Eva ;

Zambrana, Francisco ;

Endozo, Raymondo ;

Bi, Wenya Linda ;

Fennessy, Fiona M. ;

Sponer, Nicole ;

Johnson, Diana ;

Laycock, Joanne ;

Shafi, Seema ;

Czyzewska-Khan, Justyna ;

Rowan, Andrew ;

Chambers, Tim ;

Matthews, Nik ;

Turajlic, Samra ;

Hiley, Crispin ;

Lee, Siow Ming ;

Forster, Martin D. ;

Ahmad, Tanya ;

Falzon, Mary ;

Borg, Elaine ;

Lawrence, David ;

Hayward, Martin ;

Kolvekar, Shyam ;

Panagiotopoulos, Nikolaos ;

Janes, Sam M. ;

Thakrar, Ricky ;

Ahmed, Asia ;

Blackhall, Fiona ;

Summers, Yvonne ;

Hafez, Dina ;

Naik, Ashwini .

NATURE, 2017, 545 (7655) :446-+

[2] Signatures of mutational processes in human cancer [J].

Alexandrov, Ludmil B. ;

Nik-Zainal, Serena ;

Wedge, David C. ;

Aparicio, Samuel A. J. R. ;

Behjati, Sam ;

Biankin, Andrew V. ;

Bignell, Graham R. ;

Bolli, Niccolo ;

Borg, Ake ;

Borresen-Dale, Anne-Lise ;

Boyault, Sandrine ;

Burkhardt, Birgit ;

Butler, Adam P. ;

Caldas, Carlos ;

Davies, Helen R. ;

Desmedt, Christine ;

Eils, Roland ;

Eyfjord, Jorunn Erla ;

Foekens, John A. ;

Greaves, Mel ;

Hosoda, Fumie ;

Hutter, Barbara ;

Ilicic, Tomislav ;

Imbeaud, Sandrine ;

Imielinsk, Marcin ;

Jaeger, Natalie ;

Jones, David T. W. ;

Jones, David ;

Knappskog, Stian ;

Kool, Marcel ;

Lakhani, Sunil R. ;

Lopez-Otin, Carlos ;

Martin, Sancha ;

Munshi, Nikhil C. ;

Nakamura, Hiromi ;

Northcott, Paul A. ;

Pajic, Marina ;

Papaemmanuil, Elli ;

Paradiso, Angelo ;

Pearson, John V. ;

Puente, Xose S. ;

Raine, Keiran ;

Ramakrishna, Manasa ;

Richardson, Andrea L. ;

Richter, Julia ;

Rosenstiel, Philip ;

Schlesner, Matthias ;

Schumacher, Ton N. ;

Span, Paul N. ;

Teague, Jon W. .

NATURE, 2013, 500 (7463) :415-+

[3] AACR Project GENIE: Powering Precision Medicine through an International Consortium [J].

Andre, Fabrice ;

Arnedos, Monica ;

Baras, Alexander S. ;

Baselga, Jose ;

Bedard, Philippe L. ;

Berger, Michael F. ;

Bierkens, Mariska ;

Calvo, Fabien ;

Cerami, Ethan ;

Chakravarty, Debyani ;

Dang, Kristen K. ;

Davidson, Nancy E. ;

Del Vecchio, Fitz Catherine ;

Dogan, Semih ;

DuBois, Raymond N. ;

Ducar, Matthew D. ;

Futreal, P. Andrew ;

Gao Jianjiong ;

Garcia, Francisco ;

Gardos, Stu ;

Gocke, Christopher D. ;

Gross, Benjamin E. ;

Guinney, Justin ;

Heins, Zachary J. ;

Hintzen, Stephanie ;

Horlings, Hugo ;

Hudecek, Jan ;

Hyman, David M. ;

Kamel-Reid, Suzanne ;

Kandoth, Cyriac ;

Kinyua, Walter ;

Kumari, Priti ;

Kundra, Ritika ;

Ladanyi, Marc ;

Lefebvre, Celine ;

LeNoue-Newton, Michele L. ;

Lepisto, Eva M. ;

Levy, Mia A. ;

Lindeman, Neal, I ;

Lindsay, James ;

Liu, David ;

Lu Zhibin ;

MacConaill, Laura E. ;

Ian, Maurer ;

Maxwell, David S. ;

Meijer, Gerrit A. ;

Meric-Bernstam, Funda ;

Micheel, Christine M. ;

Miller, Clinton ;

Mills, Gordon .

CANCER DISCOVERY, 2017, 7 (08) :818-831

[4] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[5] Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer [J].

Gainor, Justin F. ;

Dardaei, Leila ;

Yoda, Satoshi ;

Friboulet, Luc ;

Leshchiner, Ignaty ;

Katayama, Ryohei ;

Dagogo-Jack, Ibiayi ;

Gadgeel, Shirish ;

Schultz, Katherine ;

Singh, Manrose ;

Chin, Emily ;

Parks, Melissa ;

Lee, Dana ;

DiCecca, Richard H. ;

Lockerman, Elizabeth ;

Huynh, Tiffany ;

Logan, Jennifer ;

Ritterhouse, Lauren L. ;

Le, Long P. ;

Muniappan, Ashok ;

Digumarthy, Subba ;

Channick, Colleen ;

Keyes, Colleen ;

Getz, Gad ;

Dias-Santagata, Dora ;

Heist, Rebecca S. ;

Lennerz, Jochen ;

Sequist, Lecia V. ;

Benes, Cyril H. ;

Iafrate, A. John ;

Mino-Kenudson, Mari ;

Engelman, Jeffrey A. ;

Shaw, Alice T. .

CANCER DISCOVERY, 2016, 6 (10) :1118-1133

[6] Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing [J].

Gerlinger, Marco ;

Rowan, Andrew J. ;

Horswell, Stuart ;

Larkin, James ;

Endesfelder, David ;

Gronroos, Eva ;

Martinez, Pierre ;

Matthews, Nicholas ;

Stewart, Aengus ;

Tarpey, Patrick ;

Varela, Ignacio ;

Phillimore, Benjamin ;

Begum, Sharmin ;

McDonald, Neil Q. ;

Butler, Adam ;

Jones, David ;

Raine, Keiran ;

Latimer, Calli ;

Santos, Claudio R. ;

Nohadani, Mahrokh ;

Eklund, Aron C. ;

Spencer-Dene, Bradley ;

Clark, Graham ;

Pickering, Lisa ;

Stamp, Gordon ;

Gore, Martin ;

Szallasi, Zoltan ;

Downward, Julian ;

Futreal, P. Andrew ;

Swanton, Charles .

NEW ENGLAND JOURNAL OF MEDICINE, 2012, 366 (10) :883-892

[7] Attack of the clones [J].

Govindan, Ramaswamy .

SCIENCE, 2014, 346 (6206) :169-170

[8]

Goyal L, 2017, CANCER DISCOV, V7, P1

[9] Distinct subclonal tumour responses to therapy revealed by circulating cell-free DNA [J].

Gremel, G. ;

Lee, R. J. ;

Girotti, M. R. ;

Mandal, A. K. ;

Valpione, S. ;

Garner, G. ;

Ayub, M. ;

Wood, S. ;

Rothwell, D. G. ;

Fusi, A. ;

Wallace, A. ;

Brady, G. ;

Dive, C. ;

Dhomen, N. ;

Lorigan, P. ;

Marais, R. .

ANNALS OF ONCOLOGY, 2016, 27 (10) :1959-1965

[10] Collaborating to Compete: Blood Profiling Atlas in Cancer (BloodPAC) Consortium [J].

Grossman, R. L. ;

Abel, B. ;

Angiuoli, S. ;

Barrett, J. C. ;

Bassett, D. ;

Bramlett, K. ;

Blumenthal, G. M. ;

Carlsson, A. ;

Cortese, R. ;

DiGiovanna, J. ;

Davis-Dusenbery, B. ;

Dittamore, R. ;

Eberhard, D. A. ;

Febbo, P. ;

Fitzsimons, M. ;

Flamig, Z. ;

Godsey, J. ;

Goswami, J. ;

Gruen, A. ;

Ortuno, F. ;

Han, J. ;

Hayes, D. ;

Hicks, J. ;

Holloway, D. ;

Hovelson, D. ;

Johnson, J. ;

Juhl, H. ;

Kalamegham, R. ;

Kamal, R. ;

Kang, Q. ;

Kelloff, G. J. ;

Klozenbuecher, M. ;

Kolatkar, A. ;

Kuhn, P. ;

Langone, K. ;

Leary, R. ;

Loverso, P. ;

Manmathan, H. ;

Martin, A-M ;

Martini, J. ;

Miller, D. ;

Mitchell, M. ;

Morgan, T. ;

Mulpuri, R. ;

Nguyen, T. ;

Otto, G. ;

Pathak, A. ;

Peters, E. ;

Philip, R. ;

Posadas, E. .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2017, 101 (05) :589-592

← 1 2 3 4 →