Attempts to overcome drug resistance are central to both clinical and basic molecular research in cancer chemotherapy. Temple's focus is on ovarian cancer with its TTX335o (novel target specific drug) and TTX335oDX (early detection for ovarian cancer). After winning an Eurostars Grant in 2019, Temple has been able to validate the target, elucidate its mechanism and show early promising in-vivo results in ovarian cancer, with the possibility of expanding it to other solid tumors, such as pancreatic.
Ovarian cancer is currently regarded as one of the most common cancer types among women. This type of cancer is rarely diagnosed at its early stages, making the treatment of this cancer at an advanced stage difficult. Typically, the treatment of ovarian cancer requires both cytoreductive surgery and platinum/taxane combination chemotherapy. Initially, 50–80% of patients with advanced disease will achieve complete clinical response. Unfortunately, most will relapse within 18 months with chemoresistant disease. Chemoresistance greatly limits the range of possibilities for subsequent treatments, because some tumors become resistant not only to the initial drug but also to new therapeutic agents with different mechanisms of action.
We have recently identified a never before drugged target as an ovarian cancer cell-specific target. Targeting it with its monoclonal antibody induced cell death and reduced tumor growth through a novel mechanism, without affecting normal cells. Target protein was detected in 98% of ovarian cancer tissues collected from 900 patients with various stages and histology, localized in the nucleus and cytoplasm of tumor cells. Our recent finding revealed that the risk of death among ovarian cancer patients with more cytoplasmic than nuclear target levels was particularly high during the first years after diagnosis. Intriguingly cytoplasmic target expression correlates with poor survival.
More importantly we developed target specific peptides that significantly induces ovarian cancer cell death both in vitro and in vivo. The optimized peptides, therefore, could be classified as a breakthrough therapy where currently there is a large unmet medical need, with potential application in other estrogen receptors pathway affected cancers. Strikingly, peptides are also effective in cells resistant to chemotherapy (e.g., docetaxel or cisplatin) as in sensitive cells. This is particularly important in the treatment of ovarian cancer patients, who often experience recurrent disease, which is refractory to treatment. Further, determining effectiveness of these peptides on cells resistant to radiotherapy and sensitive to radiotherapy, like breast cancer, is valuable. The value of this discovery is that in addition to ovarian cancer, this target, which is overexpressed in non-small cell lung, breast, thyroid, gastric, and colorectal cancer, could offer an interesting opportunity to expand therapeutic repertoire to other solid tumors.