2. Academic Validation
  3. Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach

Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach

  • Int J Mol Sci. 2018 Jul 31;19(8):2237. doi: 10.3390/ijms19082237.
Lidija Covic 1 2 3,  Athan Kuliopulos 4 5 6
Affiliations

Affiliations

  • 1 Division of Hematology/Oncology, Tufts Medical Center, Boston, MA 02111, USA. lcovic@tuftsmedicalcenter.org.
  • 2 Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA. lcovic@tuftsmedicalcenter.org.
  • 3 Center for Hemostasis and Thrombosis Research, Tufts Medical Center, Boston, MA 02111, USA. lcovic@tuftsmedicalcenter.org.
  • 4 Division of Hematology/Oncology, Tufts Medical Center, Boston, MA 02111, USA. athan.kuliopulos@tufts.edu.
  • 5 Department of Medicine, Tufts Medical Center, Boston, MA 02111, USA. athan.kuliopulos@tufts.edu.
  • 6 Center for Hemostasis and Thrombosis Research, Tufts Medical Center, Boston, MA 02111, USA. athan.kuliopulos@tufts.edu.
PMID: 30065181 DOI: 10.3390/ijms19082237
Abstract

The G-protein coupled receptors (GPCRs) belong to a large family of diverse receptors that are well recognized as pharmacological targets. However, very few of these receptors have been pursued as oncology drug targets. The Protease-activated Receptor 1 (PAR1), which is a G-protein coupled receptor, has been shown to act as an oncogene and is an emerging anti-cancer drug target. In this paper, we provide an overview of PAR1's biased signaling role in metastatic cancers of the breast, lungs, and ovaries and describe the development of PAR1 inhibitors that are currently in clinical use to treat acute coronary syndromes. PAR1 Inhibitor PZ-128 is in a Phase II clinical trial and is being developed to prevent ischemic and thrombotic complication of patients undergoing cardiac catheterization. PZ-128 belongs to a new class of cell-penetrating, membrane-tethered Peptides named pepducins that are based on the intracellular loops of receptors targeting the receptor G-protein interface. Application of PZ-128 as an anti-metastatic and anti-angiogenic therapeutic agent in breast, lung, and ovarian Cancer is being reviewed.

Keywords

GPCRs; PAR1; breast; invasion; lung and ovarian cancer; pepducin therapy.

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