Dr Felicity May – Development and validation of predictive biomarkers in potentially hormone responsive gynaecological cancers
Patients are often diagnosed with gynaecological cancers after their disease has advanced to a stage when they cannot be cured by surgical removal of the cancer.
It is important to identify effective drugs with which to treat gynaecological cancer patients. Such drugs would slow or halt the progression of the disease to both prolong and improve the quality of women’s lives. Further, it is important to be able to distinguish which women will benefit from any novel drug.
A recent large international clinical trial called PARAGON tested potential drugs called aromatase inhibitors, which prevent the synthesis of oestrogens, in gynaecological cancers, including some rare subtypes. These drugs are used extensively in breast cancer and evidence indicates that they should be effective in carefully-selected gynaecological cancers. Tissue has now been collected from tumours of patients within the PARAGON clinical trial.
The overall aim of our research is to develop tests that will allow clinicians to distinguish which gynaecological cancer patients will benefit from treatment with aromatase inhibitors. The rationale is that only patients who will benefit will be treated, and that patients who will not benefit will receive alternative treatments.
This research investigated the effects of oestrogen in in vitro models of different gynaecological cancers: ovarian cancer, endometrial cancer, endometrial stromal sarcoma and granulosa cell tumour. Effects were evaluated at both the genetic and protein levels, with the subsequent consequences on cell growth and proliferation being measured.
The information gained from these in vitro studies was extended with analyses of results from archival tumour tissue material from women with ovarian cancer, endometrial cancer, endometrial stromal sarcoma, granulosa cell tumour and leiomyosarcoma. Analyses were designed to identify the likelihood of each cancer’s responsiveness to oestrogen-based therapy.
We have identified novel molecules that can now be evaluated to determine if their measurement will achieve the goals described above.
Ultimately, the information described above will be combined with the data gathered from the TransPARAGON and PARAGON studies which identify the effectiveness of hormonal therapy on gynaecological malignancies with known oestrogen or progesterone receptor status. This information will enable hopefully the treatment of more women with gynaecological cancers by hormonal therapy. Treatment would either be with curative intent or be intended to prolong patient survival and minimise detrimental symptoms associated with cytotoxic treatment strategies.