New anti-cancer drug breakthrough for prostate cancer

Novel anti-cancer agents induce the degradation of the c-Met oncoprotein in the lysosome as demonstrated by confocal microscopy in tumour cells

A new anti-cancer drug for prostate cancer overcomes the twin problems plaguing researchers for decades. It halts metastasis (tumour spread) and drug resistance.

Developed by Griffith University researcher Professor Des Richardson and colleagues from the University of Sydney, the drug known as DpC inhibits prostate specific antigen (PSA) as well as suppressing both androgen-dependent and independent arms of androgen receptor signalling.

“The current gold standard for prostate cancer treatment is androgen deprivation therapy to inhibit androgen receptors but eventually treatment leads to resistance in most men,’’ Professor Richardson said.

“This drug is the first to exhibit such potent androgen receptor suppression, critical for overcoming the development of androgen resistance, a major killer in prostate cancer.”

In a article published in the FASEB Journal, Professor Richardson and colleagues examined the effect of these new anti-cancer agents (including DpC) on prostate cancer.

“Our results demonstrate that our drug unexpectedly overcomes deadly oncogenic signalling by the hormone, testosterone,’’ he said.

“This finding was totally unexpected and very exciting, as for the first time we may be able to treat patients using a new therapy that is miles ahead of the current standard anti-cancer chemotherapy for prostate cancer, Enzalutamide”.

He said another important aspect of the paper was the finding that DpC could markedly reduce the expression of the well-known indicator of prostate specific antigen — PSA.

“PSA is a bad guy in prostate cancer patients, and the fact that DpC could markedly ablate this indicator was again very surprising and could be part of the way these drugs work to block the spread of prostate cancer.”

Professor Richardson is a new appointee (Alan Mackay Sim Distinguished Chair of Cancer Cell Biology and NHMRC Senior Principal Research Fellow) at the Griffith Institute for Drug Discovery based at Griffith University.

Over the past 25 years he has been developing unique anti-cancer drugs (dipyridyl thiosemicarbazones such as “DpC”) that have entered multi-centre Phase I clinical trials for the treatment for a range of highly resistant and difficult to treat tumours.

The current research was a collaboration with Dr Zaklina Kovacevic (University of Sydney), who was mentored by Professor Richardson through her PhD studies and also multiple post-doctoral fellowships over a period of 14 years leading to over 70 joint publications in quality international journals.