Prostate
cancer is the most common cancer diagnosed in Australia and the fourth leading
cause of death among Australian males. There is a need to improve therapy for
prostate cancer as the prognosis remains poor for men with metastatic disease.
ATM-3507 is a novel therapy targeting Tpm3.1, a tropomyosin isoform that is a
key component of the cytoskeleton and essential for cancer cell survival. This
novel drug has the capacity to enhance the effect of microtubule targeting
cytotoxic drugs (i.e. the taxanes and vinca alkaloids). ATM-3507 has previously
been shown to have activity against a broad range of solid and haematological
cancer cell lines in vitro. ATM-3507 has also been shown to have
synergistic activity in combination with the vinca alkaloid vincristine in a
neuroblastoma mouse xenograft model. We report
our data confirming that ATM-3507 has activity against the prostate cell lines
DU145, PC3 and LNCaP in vitro with half
maximal inhibitory concentration (IC50) estimates in the 1-5 µM range.
Further in vitro studies have shown
evidence of synergy between ATM-3507 and docetaxel, vinorelbine and vincristine
in vitro against PC3 and DU145 prostate cancer lines. A xenograft model in
Balb/c nude mice (using subcutaneously injected DU145 cells) has shown evidence
of synergy between ATM-3507 and docetaxel compared to either drug as a single
agent, with an excellent toxicity profile. For example, mean tumour volumes
after 32 days therapy in the ATM-3507 plus docetaxel group were significantly
lower than the ATM-3507 monotherapy group (two-way ANOVA, p<0.01). This
suggests that ATM-3507 may be a useful therapy to improve the treatment of
prostate cancer whilst reducing toxicity. These data are part of a translational
research project that aims to progress to a first-in-human trial pending safety
and toxicology studies.