DDX3 is overexpressed in various forms of cancer but its oncogenic role in breast cancer has been studied most extensively.The treatment of breast cancer has dramatically benefited with the introduction of estrogen and progesterone receptors as diagnostic and prognostic biomarkers, but for triple negative and aggressive breast cancers the survival expectancy is still poor.
Screening patients for the presence of estrogen and progesterone receptors, as well as the overexpression of the HER2 protein can direct the therapy and thus the chance of successful treatment and survival. Patients whose cancer cells are positive for HER2 have a more aggressive disease and may be treated with the Herceptin, a monoclonal antibody that targets HER2 and improves the prognosis, whilst patients who do not test positive for estrogen (ER) and progesterone receptors (PR) will not be able to respond to hormone therapy.
Treatment with our DDX3 inhibitors would follow a similar approach of pre screening the patient’s cancer cells for DDX3 overexpression, potentially offering an integration or alternative to available treatments.
Luckily mild to moderate forms of breast cancer respond well to available treatment options, but unfortunately metastatic breast cancers and triple negative types still have a very poor outcome. Even with optimal treatment the ten year survival expectancy is no more than 10%. Triple negative breast cancer (ER, PR and HER2) is considered especially aggressive and difficult to treat. Also, the cancer is more likely to spread and recur.
Taking this into consideration our DDX3 Inhibitors were tested on metastatic breast cancer cell lines expressing DDX3, showing relevant activity in all compounds and very positive results in one specific compound. The possibilities for DDX3 based treatment in triple negative breast cancer is also under investigation.
Preliminary data in vivo showed no toxicity and a good tissues distribution. The development of our antitumor pipeline includes further improvement of the antitumor activity and the optimisation of the delivery and distribution in the body of the lead coumpounds.