细胞凋亡
癌症
单克隆抗体
信号转导
医学
癌症研究
癌细胞
靶向治疗
生物信息学
生物
免疫学
细胞生物学
抗体
内科学
生物化学
作者
Bora Lim,Joshua E. Allen,Varun V. Prabhu,Mala K. Talekar,Niklas Finnberg,Wafik S. El‐Deiry
标识
DOI:10.1517/14728222.2015.1049838
摘要
While apoptosis is critical for maintaining homeostasis in normal cells, defective apoptosis contributes to the survival of cancer cells. TNF-related apoptosis-inducing ligand (TRAIL)-targeted therapy has attracted significant effort for treating cancer, but the clinical results have revealed limitations. The authors review the current status of development of TRAIL-targeted therapy with an outlook towards the future.Recombinant human proteins, small molecules and agonistic monoclonal antibodies targeting death receptors that trigger TRAIL-mediated apoptosis are covered in this article. The authors review both intrinsic and extrinsic apoptotic pathways, highlighting how the apoptosis serves as a promising therapeutic target. They also review different categories of TRAIL pathway targeting agents and provide a brief overview of clinical trials using these agents. The authors discuss the limitations of conventional approaches for targeting the TRAIL pathway as well as future directions.The development of better combination partners for pro-apoptotic TRAIL pathway modulators including novel agents inhibiting anti-apoptotic molecules or targeting alternative resistance pathways may improve the chances for anti-tumor responses in the clinic. Developing predictive biomarkers via circulating tumor cells/DNA, apoptosis signal products, and genetic signatures/protein biomarkers from tumor tissue are also suggested as future directions.
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