Hæmning af Sarcoplasmatisk/Endoplasmatisk Reticulum Calcium ATP-ase 2 ved hjælp af thapsigargin-promedikamenterne G202 og G114 med henblik på behandling af prostatakræft

Jeanne Paustian, Jarl Esbensen, Nicolai Lond Frisk, Edelbo Henriksen, Beatriche Louise, Cecilie Brunshøj Pedersen & Anja Fabrin Hjort

Student thesis: Termpaper

Abstract

The purpose of this review is to gather the information currently available regarding treatment of prostate cancer with thapsigargin-based drugs. This is done in order to examine the potential of the prodrug and the status of its development. Parts of the review are based on articles published in the end of November 2012. Thapsigargin as it is found in nature is an effective inhibitor of SERCA pumps in cells, and the effect can be maintained despite the fact that it is necessary to change the molecular structure of thapsigargin in order to form a prodrug, which is only selectively toxic. By attaching peptide chains onto thapsigargin analogs these can be designed to target specific hydrolases, such as PSA or PSMA, thus ensuring that the cytotoxin is released only in or closely around the prostate tumor. In vivo experiments on mice have shown a tumor regressive effect, which seems to exceed that of the traditional chemotherapeutic treatments when doses were administered that resulted in a mortality rate not exceeding 10 %. Phase 1 dose escalation trials on humans have been done in order to establish the maximum dose tolerated. Next phase is to determine the effectiveness of this dose on patients with cancer. There are therefore incitements for further research - including trials – and reasons for a cautious optimism.

EducationsBasic - Bachelor Study Program in Natural Science, (Bachelor Programme) Basic
LanguageDanish
Publication date16 Jan 2013
SupervisorsHans Ramløv

Keywords

  • Thapsigargin
  • Prostate Cancer
  • Prodrug
  • G202
  • G114
  • G115