Targeted therapies

Definition

A targeted therapy is one that has been developed to affect a specific target, such as an enzyme or receptor. Targeted therapies can either block or increase the function of their target in order to treat a given disease; in this case, cancer.

Latest Research and Reviews

  • Research | | open

    Resistance towards VEGF-centered anti-angiogenic therapy is an important clinical challenge. Here, the authors show that mast cells mediate resistance to anti-angiogenetic inhibitors by altering the proliferative and organizational state of endothelial cells through mobilization of FGF-1 and GM-CSF from the tumor matrix and secretion of FGF-2.

    • M. Wroblewski
    • , R. Bauer
    • , M. Cubas Córdova
    • , F. Udonta
    • , I. Ben-Batalla
    • , K. Legler
    • , C. Hauser
    • , J. Egberts
    • , M. Janning
    • , J. Velthaus
    • , C. Schulze
    • , K. Pantel
    • , C. Bokemeyer
    •  & S. Loges
  • Research |

    Mutations in SPOP, the gene encoding a component of the E3 ubiquitin ligase complex, impair ubiquitination-dependent degradation of BRD2, BRD3 and BRD4 proteins and result in activation of ATK–mTORC1 signaling and resistance to BET inhibitors. Pharmacological blockade of AKT represents a viable strategy to restore the sensitivity of SPOP-mutant prostate tumors to BET inhibitors. These results, together with findings by Dai et al. and Janouskova et al., uncover a new nongenetic mechanism of resistance to BET inhibition involving cancer-type-specific mutations in SPOP, and support the evaluation of SPOP mutation status to inform the administration of BET inhibitors in the clinic.

    • Pingzhao Zhang
    • , Dejie Wang
    • , Yu Zhao
    • , Shancheng Ren
    • , Kun Gao
    • , Zhenqing Ye
    • , Shangqian Wang
    • , Chun-Wu Pan
    • , Yasheng Zhu
    • , Yuqian Yan
    • , Yinhui Yang
    • , Di Wu
    • , Yundong He
    • , Jun Zhang
    • , Daru Lu
    • , Xiuping Liu
    • , Long Yu
    • , Shimin Zhao
    • , Yao Li
    • , Dong Lin
    • , Yuzhuo Wang
    • , Liguo Wang
    • , Yu Chen
    • , Yinghao Sun
    • , Chenji Wang
    •  & Haojie Huang
  • Research |

    Different mutations found in endometrial and prostate tumors affecting the substrate-recognition domain of SPOP, a component of the E3 ubiquitin ligase complex, result in opposing degradation activity of BET proteins and response to BET inhibitors. This work, along with findings by Zhang et al. and Dai et al., highlights the divergent effects of recurrent mutations affecting different residues within the same functional domain of SPOP and provides scientific rationale to guide the administration of BET inhibitors in endometrial and prostate cancer patients harboring SPOP mutations.

    • Hana Janouskova
    • , Geniver El Tekle
    • , Elisa Bellini
    • , Namrata D Udeshi
    • , Anna Rinaldi
    • , Anna Ulbricht
    • , Tiziano Bernasocchi
    • , Gianluca Civenni
    • , Marco Losa
    • , Tanya Svinkina
    • , Craig M Bielski
    • , Gregory V Kryukov
    • , Luciano Cascione
    • , Sara Napoli
    • , Radoslav I Enchev
    • , David G Mutch
    • , Michael E Carney
    • , Andrew Berchuck
    • , Boris J N Winterhoff
    • , Russell R Broaddus
    • , Peter Schraml
    • , Holger Moch
    • , Francesco Bertoni
    • , Carlo V Catapano
    • , Matthias Peter
    • , Steven A Carr
    • , Levi A Garraway
    • , Peter J Wild
    •  & Jean-Philippe P Theurillat
  • Research |

    Recurrent mutations in SPOP-encoding a Cullin 3-based E3 ubiquitin ligase- in prostate cancer disrupt the recognition and degradation of ubiquitination substrates, including BET proteins. Consequently, stability of BET proteins is enhanced and this increases the resistance to BET inhibitors in SPOP-mutant prostate tumors. These results, together with those in Janouskova et al. and Zhang et al., uncover a novel non genetic mechanism of resistance to BET inhibition involving cancer type-specific mutations in SPOP, and support the evaluation of SPOP mutations to inform the administration of BET inhibitors in the clinic.

    • Xiangpeng Dai
    • , Wenjian Gan
    • , Xiaoning Li
    • , Shangqian Wang
    • , Wei Zhang
    • , Ling Huang
    • , Shengwu Liu
    • , Qing Zhong
    • , Jianping Guo
    • , Jinfang Zhang
    • , Ting Chen
    • , Kouhei Shimizu
    • , Francisco Beca
    • , Mirjam Blattner
    • , Divya Vasudevan
    • , Dennis L Buckley
    • , Jun Qi
    • , Lorenz Buser
    • , Pengda Liu
    • , Hiroyuki Inuzuka
    • , Andrew H Beck
    • , Liewei Wang
    • , Peter J Wild
    • , Levi A Garraway
    • , Mark A Rubin
    • , Christopher E Barbieri
    • , Kwok-Kin Wong
    • , Senthil K Muthuswamy
    • , Jiaoti Huang
    • , Yu Chen
    • , James E Bradner
    •  & Wenyi Wei

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