Targeted Therapy for Cancer in the Genomic Era

被引:39
作者
Afghahi, Anosheh [1 ]
Sledge, George W., Jr. [1 ]
机构
[1] Stanford Univ, Sch Med, Div Med Oncol, Stanford, CA 94305 USA
关键词
Cancer genomics; CTLA-4; Erb2; immunotherapy; PD-1; PDL-1; CELL LUNG-CANCER; BREAST-CANCER; MUTATIONAL LANDSCAPE; CLINICAL-RESPONSE; TYROSINE KINASE; EGFR MUTATIONS; TRASTUZUMAB; RESISTANCE; GEFITINIB; BLOCKADE;
D O I
10.1097/PPO.0000000000000135
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The advent of cancer genomics has led to the development of many highly successful targeted therapies, primarily inhibitors of growth factor receptors and related kinases, including imatinib for chronic myeloid leukemia and trastuzumab for HER2-positive breast cancer. This approach has become highly successful for certain cancers. However, as the list of targeted therapies expands, their efficacy becomes more limited, and toxicity accumulates. What we have learned in the past decades is that while the targeted therapeutics approach may be highly successful in less complex tumors, cancers defined by carcinogen-induced genomic chaos, such a UV-induced melanoma or tobacco-induced lung cancer, are driven by a multitude of competing molecular pathways and, as such, are not as successfully managed by a similar approach. Luckily, in the past years, the field of cancer immunotherapy has become more fully developed with the emergence of checkpoint blockade inhibitor therapy. These promising new agents are particularly well suited for tumors with a high mutational burden due to underlying genomic disarray. While still in its infancy, we predict that cancer immunotherapy will offer a better alternative to our current targeted approach and eagerly await the results of several ongoing clinical trials that will elucidate this new direction in cancer therapy.
引用
收藏
页码:294 / 298
页数:5
相关论文
共 35 条
[1]  
Abrams Jeffrey, 2014, Am Soc Clin Oncol Educ Book, P71, DOI 10.14694/EdBook_AM.2014.34.71
[2]   ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics [J].
Arteaga, Carlos L. ;
Engelman, Jeffrey A. .
CANCER CELL, 2014, 25 (03) :282-303
[3]   A review of the European LeukemiaNet recommendations for the management of CML [J].
Baccarani, Michele ;
Castagnetti, Fausto ;
Gugliotta, Gabriele ;
Rosti, Gianantonio .
ANNALS OF HEMATOLOGY, 2015, 94 :S141-S147
[4]   Activating HER2 Mutations in HER2 Gene Amplification Negative Breast Cancer [J].
Bose, Ron ;
Kavuri, Shyam M. ;
Searleman, Adam C. ;
Shen, Wei ;
Shen, Dong ;
Koboldt, Daniel C. ;
Monsey, John ;
Goel, Nicholas ;
Aronson, Adam B. ;
Li, Shunqiang ;
Ma, Cynthia X. ;
Ding, Li ;
Mardis, Elaine R. ;
Ellis, Matthew J. .
CANCER DISCOVERY, 2013, 3 (02) :224-237
[5]   The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers [J].
Diaz, Luis A., Jr. ;
Williams, Richard T. ;
Wu, Jian ;
Kinde, Isaac ;
Hecht, J. Randolph ;
Berlin, Jordan ;
Allen, Benjamin ;
Bozic, Ivana ;
Reiter, Johannes G. ;
Nowak, Martin A. ;
Kinzler, Kenneth W. ;
Oliner, Kelly S. ;
Vogelstein, Bert .
NATURE, 2012, 486 (7404) :537-540
[6]   Database of Genomic Biomarkers for Cancer Drugs and Clinical Targetability in Solid Tumors [J].
Dienstmann, Rodrigo ;
Jang, In Sock ;
Bot, Brian ;
Friend, Stephen ;
Guinney, Justin .
CANCER DISCOVERY, 2015, 5 (02) :118-123
[7]   Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. [J].
Druker, BJ ;
Talpaz, M ;
Resta, DJ ;
Peng, B ;
Buchdunger, E ;
Ford, JM ;
Lydon, NB ;
Kantarjian, H ;
Capdeville, R ;
Ohno-Jones, S ;
Sawyers, CL .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) :1031-1037
[8]   Resistance to Targeted Therapies: Refining Anticancer Therapy in the Era of Molecular Oncology [J].
Ellis, Lee M. ;
Hicklin, Daniel J. .
CLINICAL CANCER RESEARCH, 2009, 15 (24) :7471-7478
[9]   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
[10]   Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer [J].
Hammerman, Peter S. ;
Jaenne, Pasi A. ;
Johnson, Bruce E. .
CLINICAL CANCER RESEARCH, 2009, 15 (24) :7502-7509