Therapeutic targeting of the p53 pathway in cancer stem cells

被引:35
|
作者
Prabhu, Varun V. [1 ]
Allen, Joshua E. [1 ,2 ]
Hong, Bo [1 ]
Zhang, Shengliang [1 ]
Cheng, Hairong [1 ]
El-Deiry, Wafik S. [1 ]
机构
[1] Penn State Coll Med, Penn State Hershey Canc Inst, Dept Med Hematol Oncol, Lab Translat Oncol & Expt Canc Therapeut, Hershey, PA 17033 USA
[2] Univ Penn, Sch Med, Biochem & Mol Biophys Grad Grp, Philadelphia, PA 19104 USA
关键词
cancer; cancer stem cells; cancer therapy; p53; pathway; p53 pathway restoration; restoration; stem cells; EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR; HEMATOPOIETIC STEM; SIDE POPULATION; SELF-RENEWAL; RESTORATION; NOTCH; DIFFERENTIATION; ACTIVATION; REPRESSION;
D O I
10.1517/14728222.2012.726985
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Cancer stem cells (CSCs) are a high profile drug target for cancer therapeutics due to their indispensable role in cancer progression, maintenance and therapeutic resistance. Restoring wild-type (WT) p53 function is an attractive new therapeutic approach for the treatment of cancer due to the well-described powerful tumor suppressor function of p53. As emerging evidence intimately links p53 and stem cell biology, this approach also provides an opportunity to target CSCs. Areas covered: This review covers the therapeutic approaches to restore the function of WT p53, cancer and normal stem cell biology in relation to p53 and the downstream effects of p53 on CSCs. Expert opinion: The restoration of WT p53 function by targeting p53 directly, its interacting proteins or its family members holds promise as a new class of cancer therapies. This review examines the impact that such therapies may have on normal and CSCs based on the current evidence linking p53 signaling with these populations.
引用
收藏
页码:1161 / 1174
页数:14
相关论文
共 50 条
  • [41] Targeting the MDM2/p53 pathway in gastrointestinal stromal tumors: Therapeutic potential
    Henze, Jorn
    Muhlenberg, Thomas
    Simon, Susanne
    Fletcher, Jonathan A.
    Schuler, Martin
    Bauer, Sebastian
    MOLECULAR CANCER THERAPEUTICS, 2009, 8 (12)
  • [42] Targeting p53
    Madrid, LV
    SCIENTIST, 1999, 13 (04): : 14 - 14
  • [43] Targeting p53 as a promising therapeutic option for cancer by re-activating the wt or mutant p53's tumor suppression
    Wesierska-Gadek, Jozefa
    FUTURE MEDICINAL CHEMISTRY, 2018, 10 (07) : 755 - 777
  • [44] FAK and Nanog Cross Talk with p53 in Cancer Stem Cells
    Golubovskaya, Vita M.
    ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2013, 13 (04) : 576 - 580
  • [45] Increased Arf/p53 activity in stem cells, aging and cancer
    Carrasco-Garcia, Estefania
    Moreno, Manuel
    Moreno-Cugnon, Leire
    Matheu, Ander
    AGING CELL, 2017, 16 (02): : 219 - 225
  • [46] Differential regulation of the REGγ–proteasome pathway by p53/TGF-β signalling and mutant p53 in cancer cells
    Amjad Ali
    Zhuo Wang
    Junjiang Fu
    Lei Ji
    Jiang Liu
    Lei Li
    Hui Wang
    Jiwu Chen
    Carlos Caulin
    Jeffrey N. Myers
    Pei Zhang
    Jianru Xiao
    Bianhong Zhang
    Xiaotao Li
    Nature Communications, 4
  • [47] Differential regulation of the REGγ-proteasome pathway by p53/TGF-β signalling and mutant p53 in cancer cells
    Ali, Amjad
    Wang, Zhuo
    Fu, Junjiang
    Ji, Lei
    Liu, Jiang
    Li, Lei
    Wang, Hui
    Chen, Jiwu
    Caulin, Carlos
    Myers, Jeffrey N.
    Zhang, Pei
    Xiao, Jianru
    Zhang, Bianhong
    Li, Xiaotao
    NATURE COMMUNICATIONS, 2013, 4
  • [48] Overcoming therapeutic resistance in pancreatic cancer: Emerging opportunities by targeting BRCAs and p53
    Calheiros, Juliana
    Corbo, Vincenzo
    Saraiva, Lucilia
    BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2023, 1878 (04):
  • [49] p53: An Attractive Therapeutic Target for Cancer
    Patel, Krupa R.
    Patel, Hitesh D.
    CURRENT MEDICINAL CHEMISTRY, 2020, 27 (22) : 3706 - 3734
  • [50] Therapeutic Targeting of the Warburg Effect in Pancreatic Cancer Relies on an Absence of p53 Function
    Rajeshkumar, N. V.
    Dutta, Prasanta
    Yabuuchi, Shinichi
    de Wilde, Roeland F.
    Martinez, Gary V.
    Le, Anne
    Kamphorst, Jurre J.
    Rabinowitz, Joshua D.
    Jain, Sanjay K.
    Hidalgo, Manuel
    Dang, Chi V.
    Gillies, Robert J.
    Maitra, Anirban
    CANCER RESEARCH, 2015, 75 (16) : 3355 - 3364