Systems Biology Approaches to Pancreatic Cancer Detection, Prevention and Treatment

被引:7
作者
Alian, Osama M. [1 ]
Philip, Philip A. [2 ]
Sarkar, Fazlul H. [1 ,2 ]
Azmi, Asfar S. [2 ]
机构
[1] Wayne State Univ, Sch Med, Karmanos Canc Inst, Dept Oncol, Detroit, MI 48201 USA
[2] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA
关键词
Pancreatic neoplasm; pancreatic cancer; pancreatic ductal adenocarcinoma; network pharmacology; network medicine; systems biology; systems medicine; synergistic drug pairs; network targeted drugs; DRUG TOXICITY; HEALTH-CARE; DIAGNOSIS; TARGETS; THERAPY; NETWORK; MICRORNA; PHARMACOLOGY; EXPRESSION; DISCOVERY;
D O I
10.2174/138161282001140113124643
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Pancreatic cancer [PC] is a complex disease harboring multiple genetic alterations. It is now well known that deregulation in the expression and function of oncogenes and tumor suppressor genes contributes to the development and progression of PC. The last 40 years have not seen any major improvements in the dismal overall cure rate for PC where drug resistance is an emerging and recurring obstacle for successful treatment of PC. Additionally, the lack of molecular biomarkers for patient selection limits drug availabilities for tailored therapy for patients diagnosed with PC. The very high failure rate of new drugs in Phase III clinical trials in PC calls for a more robust pre-clinical and clinical testing of new compounds. In order to rationally choose combinations of targeted agents that may improve therapeutic outcome by overcoming drug resistance, one needs to apply newer research tools such as systems and network biology. These newer tools are expected to assist in the design of effective drug combinations for the treatment of PC and are expected to become an important part in any future clinical trials. In this review we will provide background information on the current state of PC research, the reasons for drug failure and how to overcome these issues using systems sciences. We conclude this review with an example on how systems and network methodologies can help in the design efficacious drug combinations for this deadly and by far incurable disease.
引用
收藏
页码:73 / 80
页数:8
相关论文
共 74 条
  • [1] Network insights on oxaliplatin anti-cancer mechanisms
    Alian, Osama M.
    Azmi, Asfar S.
    Mohammadl, Ramzi M.
    [J]. CLINICAL AND TRANSLATIONAL MEDICINE, 2012, 1
  • [2] Ansari D, 2012, ACTA ONCOL
  • [3] Systems medicine: the future of medical genomics and healthcare
    Auffray, Charles
    Chen, Zhu
    Hood, Leroy
    [J]. GENOME MEDICINE, 2009, 1
  • [4] Can network pharmacology rescue neutraceutical cancer research?
    Azmi, Asfar S.
    Mohammad, Ramzi M.
    Sarkar, Fazlul H.
    [J]. DRUG DISCOVERY TODAY, 2012, 17 (15-16) : 807 - 809
  • [5] Azmi AS, 2011, EPIGENOMICS-UK, V3, P747, DOI [10.2217/EPI.11.97, 10.2217/epi.11.97]
  • [6] Azmi AS, 2011, ONCOTARGET, V2, P378
  • [7] Proof of Concept: Network and Systems Biology Approaches Aid in the Discovery of Potent Anticancer Drug Combinations
    Azmi, Asfar S.
    Wang, Zhiwei
    Philip, Philip A.
    Mohammad, Ramzi M.
    Sarkar, Fazlul H.
    [J]. MOLECULAR CANCER THERAPEUTICS, 2010, 9 (12) : 3137 - 3144
  • [8] Systems Pharmacology to Predict Drug Toxicity: Integration Across Levels of Biological Organization
    Bai, Jane P. F.
    Abernethy, Darrell R.
    [J]. ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 53, 2013, 2013, 53 : 451 - 473
  • [9] Pancreatic cancer biology and genetics
    Bardeesy, N
    DePinho, RA
    [J]. NATURE REVIEWS CANCER, 2002, 2 (12) : 897 - 909
  • [10] Validating cancer drug targets
    Benson, John D.
    Chen, Ying-Nan P.
    Cornell-Kennon, Susan A.
    Dorsch, Marion
    Kim, Sunkyu
    Leszczyniecka, Magdalena
    Sellers, William R.
    Lengauer, Christoph
    [J]. NATURE, 2006, 441 (7092) : 451 - 456