The impact of molecular targets in cancer drug development: major hurdles and future strategies

被引:0
作者
Hebar, Alexandra [1 ]
Valent, Peter [2 ]
Selzer, Edgar [1 ]
机构
[1] Med Univ Vienna, Dept Radiat Oncol, Vienna, Austria
[2] Med Univ Vienna, Dept Med 1, Div Hematol & Hemostaseol, Vienna, Austria
关键词
cancer therapy; drug discovery and development; oncogene addiction; regulatory aspects; targeted drugs; CHRONIC MYELOID-LEUKEMIA; CELL LUNG-CANCER; TYROSINE KINASE; STEM-CELLS; PERSONALIZED MEDICINE; AMERICAN SOCIETY; CLINICAL-TRIALS; THERAPY; INHIBITOR; IMATINIB;
D O I
10.1586/ECP.12.71
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The last decades were characterized by enormous technological advances resulting in a better understanding of disease pathologies and improvement of treatment strategies. The development of targeted drugs, whose beginning can be traced back to Paul Ehrlich's theory of the 'magic bullet' approximately 100 years ago, is today widely appraised as a promising strategy to combat benign, as well as malignant, diseases. Over 40 years after US President Nixon declared the 'war on cancer', treatment outcome, especially of solid tumors in the advanced stages of disease, still lies far behind expectations. In this perspective article, the authors discuss the recent development of targeted cancer drugs and identify major hurdles. The authors further highlight future strategies that might improve and accelerate the drug-development process.
引用
收藏
页码:23 / 34
页数:12
相关论文
共 82 条
  • [1] Targeted cancer therapies
    Aggarwal, Saurabh
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2010, 9 (06) : 427 - 428
  • [2] Self-renewal and solid tumor stem cells
    Al-Hajj, M
    Clarke, MF
    [J]. ONCOGENE, 2004, 23 (43) : 7274 - 7282
  • [3] American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients With Metastatic Colorectal Carcinoma to Predict Response to Anti-Epidermal Growth Factor Receptor Monoclonal Antibody Therapy
    Allegra, Carmen J.
    Jessup, J. Milburn
    Somerfield, Mark R.
    Hamilton, Stanley R.
    Hammond, Elizabeth H.
    Hayes, Daniel F.
    McAllister, Pamela K.
    Morton, Roscoe F.
    Schilsky, Richard L.
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (12) : 2091 - 2096
  • [4] The intrinsic dynamics of enzymes plays a dominant role in determining the structural changes induced upon inhibitor binding
    Bakan, Ahmet
    Bahar, Ivet
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (34) : 14349 - 14354
  • [5] ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers
    Bergethon, Kristin
    Shaw, Alice T.
    Ou, Sai-Hong Ignatius
    Katayama, Ryohei
    Lovly, Christine M.
    McDonald, Nerina T.
    Massion, Pierre P.
    Siwak-Tapp, Christina
    Gonzalez, Adriana
    Fang, Rong
    Mark, Eugene J.
    Batten, Julie M.
    Chen, Haiquan
    Wilner, Keith D.
    Kwak, Eunice L.
    Clark, Jeffrey W.
    Carbone, David P.
    Ji, Hongbin
    Engelman, Jeffrey A.
    Mino-Kenudson, Mari
    Pao, William
    Iafrate, A. John
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (08) : 863 - 870
  • [6] A new paradigm for protein kinase inhibition: blocking phosphorylation without directly targeting ATP binding
    Bogoyevitch, Marie A.
    Fairlie, David P.
    [J]. DRUG DISCOVERY TODAY, 2007, 12 (15-16) : 622 - 633
  • [7] Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival
    Bonner, James A.
    Harari, Paul M.
    Giralt, Jordi
    Cohen, Roger B.
    Jones, Christopher U.
    Sur, Ranjan K.
    Raben, David
    Baselga, Jose
    Spencer, Sharon A.
    Zhu, Junming
    Youssoufian, Hagop
    Rowinsky, Eric K.
    Ang, K. Kian
    [J]. LANCET ONCOLOGY, 2010, 11 (01) : 21 - 28
  • [8] Cancer stem cells: lessons from leukaemia
    Bonnet, D
    [J]. CELL PROLIFERATION, 2005, 38 (06) : 357 - 361
  • [9] Glivec (ST1571, Imatinib), a rationally developed, targeted anticancer drug
    Capdeville, R
    Buchdunger, E
    Zimmermann, J
    Matter, A
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (07) : 493 - 502
  • [10] Advances in the preclinical testing of cancer therapeutic hypotheses
    Caponigro, Giordano
    Sellers, William R.
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (03) : 179 - 187