Poster Presentation & Flash Talk Presentation 28th Lorne Cancer Conference 2016

The novel anti-tropomyosin drug ATM-3507 enhances the activity of standard chemotherapy for prostate cancer in pre-clinical models (#130)

Adam Cooper 1 2 3 , Kieran Scott 1 2 3 4 , Paul De Souza 1 2 3 4 , Mila Sajinovic 1 3 4 , Jeff Hook 4 , Peter Gunning 4 , Justine Stehn 4 5
  1. Ingham Institute, Sydney, Australia
  2. Western Sydney University, Sydney, NSW, Australia
  3. CONCERT TCRC, Sydney, NSW, Australia
  4. University of New South Wales, Sydney, NSW, Australia
  5. Novogen Ltd, Hornsby, NSW, Australia
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.