Issues on targeted therapies in prostate cancer research were examined on the second day of the Prostate Cancer Translational Research in Europe meeting held in Amsterdam (NL) with experts giving an overview on current and novel experiments in the field. Prof. Jack Schalken ( Nijmegen, NL) informed the audience about the latest developments in endocrine therapy in his lecture ‘New approaches for endocrine therapy of prostate cancer: summary and discussion.’ He focused on the promising results for abiraterone acetate and MDV3100. Regarding the problems of resistance, Schalken asked: "We should find answers to questions such as How long does it take for resistance to appear? What causes it? Do the androgen receptors disappear?" Jan Trapman ( Rotterdam , NL), who moderated the discussion, asked what the EAU Research Foundation (EAURF) is doing to stimulate studies with new drugs for endocrine therapy. EAURF Chairman Prof. Peter Mulders replied: "Large phase III studies with abiraterone and MDV3100 are being performed. The Research Foundation aims to perform a site study; we will continue to be involved."
Meanwhile, Norman Maitland (York, GB) delivered a lecture on ‘Optimising targeted gene therapy for prostate cancer.’ "The GIANT consortium aims to bring together leaders in vecterology in the European Union, in order to apply their skills to prostate cancer and make translations to the clinic," he explained. “Viral vecterology is all about making better vectors that truly attach to prostate cancer cells.”
GIANT tries to promote the use of gene therapy, a therapeutic option that remains controversial since the 1980s. At present, gene therapy trials are abundant in the US but not in Europe. "Although not many people are involved in the research, there are many late-stage European trials now," said Maitland.
So far, results from GIANT are impressive. “We have established international cooperation in the field of gene therapy. This enabled us to provide a basis for the adhesion of adenovirus vectors to human blood. We also demonstrated that synthetic ‘shielding’ can prevent plasma adhesion,” according to Maitland. Also, a new generation of attachment molecules was developed, and more stable, engineered molecules that improve vector attachment. Novel, clinically applicable non-viral vectors add to the success of the project. But it does not stop there. The first clinical GIANT trial is nearing with the clinical trial design already complete. Maitland concluded: "There are many chances in the field of viral gene therapy, or biotherapy. These are exciting times, however, we should not forget that the therapy and the viruses are meant to be used to kill the disease, not the patient."A lecture titled 'A critical view on targeted therapies: from magic bullet to smart bomb' was given by Prof. John Isaacs (Baltimore, US). Examples of targeted therapies are Stealth – which is based on cell type restricted cellular processes – and Smart bomb – cell type restricted activation of a toxin for a critical cellular process with activation occurring extra-cellularly to sterilise the cancer neighbourhood. "PSA is also a target, because it is enzymatically active (not in serum) and it is present in high concentrations in prostate cancer tissue. There is practically no production of PSA in other tissues in men," Isaacs said.
There are some promising new drugs, such as proaerolysin which – through biotechnical engineering – is activated by PSA and then kills cells. Isaacs: "Furthermore, a plant called thapsia has an active substance, thapsigargin, which kills proliferating and non-proliferating cancer cells by inhibition of the SERCA pump in the cell. It effectively kills slowly proliferating cells, where standard chemotherapy is inactive," said Isaacs.
The PSMA prodrug is based on PSMA, which is expressed by the tumour vasculature of cancer cells. It kills cancer cells locally. "All of these developments would not have been possible if it was not for the cooperation between different institutions and universities, both in the US and in Europe and to funding from such as the Prostate Cancer Foundation and the Dutch Cancer Foundation," Isaacs said. He concluded by stressing that, despite high hopes, it is still not possible – and probably never will be – to treat prostate cancer by only attacking the cancer cells without affecting the healthy cells. Isaacs: "Prostate cancer treatment makes people sick, we should not deny that. However, we are not talking about chronic therapy. We should limit toxicity and develop not one magic bullet, but several."