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Funded Research 2005
Prof Shai and his team are looking at potential new treatments
for prostate cancer
Novel Chemotherapeutic Peptides for Treatment of Prostate Cancer with a New Mode of Action – Targeting the Cell Membrane
Professor Yechiel Shai, Weizmann Institute of Science, Israel
The number of target specific therapeutic drugs against cancer is limited. This is mainly due to the complexity of the transformation process, which differs greatly between difference cancer types. When specific targeting of the cancer is unavailable, one must resort to conventional treatments (surgery, radiation and chemotherapy), as in the case of prostate cancer. The problem is even more acute once metastases form. At this stage chemotherapy (ie antimetabolites, alkylating agents, etc.) is currently the preferred solution. However, most chemotherapeutic agents also affect normal mammalian cells and consequently cause severe side effects. In addition, these compounds need to penetrate the target cell to exert their function, therefore are subject to clearance by multi-drug resistance proteins (MDR). Hence, there is an urgent need to develop a new class of anticancer drugs, which can target cancer cells and overcome MDR.
The objectives of the present study are to synthesize and test new prostate cancer specific lytic peptides based on a previous study (Pardaxin, a new pharmacological tool to stimulate the arachidonic acid cascade in PC12 cells) that should overcome resistance, and perform structure-function studies in both in vitro and in vivo ( intratumor and systemic applications ). Activity will be examined against both androgen-dependent and independent prostate carcinoma cells, and by using subcutaneously and intravenously injected human prostate cancer cells in nude to create solid tumour and methastasis. Moreover, we will test the peptides for synergistic capacity with known chemotherapeutic agents in vitro and in vivo . Because the pH is slightly acidic in tumour compared with normal tissues, our aim is to modify the diastereomers such that they will be active only at acidic pH, which should make them inert to normal tissues.
Publications
Cancer Research, May 15, 2006
www.aacrjournals.org
Project commenced
May 2005
Length of project
2 years
Amount Supported
£77,000
