Ovarian Cancer

http://www.imm.ox.ac.uk/home

Worldwide, over 200,000 women are diagnosed with ovarian cancer every year

only one quarter will remain alive

5 years following the diagnosis.

Our work explores the molecular mechanisms that drive Ovarian Cancer cell growth and examines which targeted therapies can be utilised to improve the treatment of women with Ovarian Cancer.

Professor Ahmed talks about blocking a gene known as SIK2 can help overcome drug resistance in ovarian cancer.

WHAT WE DO

We set up the Ovarian Cancer Cell Laboratory in The Weatherall Institute of Molecular Medicine. Ovarian cancer is the most lethal Gynaecological malignancy. In spite of excellent response to chemotherapy, minimal residual disease persists and results in the development of chemotherapy resistant recurrent tumours. Incomplete response to primary therapy allows the development of chemotherapy resistance in ovarian cancer and this leads to a progressive disease that is difficult to treat.

PIONIR STUDY - state of the art technologies

We collaborated with Vojnovic (Oncology) and GE Healthcare on the preclinical testing of intraoperative fluorescence imaging using optical imaging probestargeting cMet oncogene. We evaluated an in‐house optical imaging system to detect sentinel lymph nodes in patients with vulval, cervical and endometrial cancers through conducting a surgical trial in collaboration with the Oncology Department’s Early Phase Clinical Trials Unit. In addition, Our PIONIR study is looking at the new imaging system to see if it can help surgeons see which lymph nodes are the first to take up fluids draining from the cancer. During surgery, we inject a dye into the cancer. This dye shines brightly under infrared light, showing us which nodes are the sentinel nodes.

Cancer cells can spread to lymph nodes through the normal circulation of body fluid. So if a patient has surgery to remove a cancer, a surgeon may also remove all the lymph nodes closest to it. The only way to find out if lymph nodes contain cancer is for a pathologist to look at them after surgery. In many cases the lymph nodes don’t show signs of containing cancer, but are removed just in case. Removing all the nodes can increase the risk of side effects or complications after surgery. If surgeons could know during surgery whether or not nearby lymph nodes contained cancer, they would only need to remove those affected. Read more

The multiwavelength fluorescence image-guided surgery imaging system:

We also developed a theranostic by combining the chemotherapeutic drug paclitaxel with a novel fluorescence‐based paclitaxel biosensor in mesoporous silica nanoparticles. We tested Ovarian Cancer initiation and progression using mouse models.

Our Collaborations within the university of oxford

Investigation of the evolution of Ovarian Cancer using the chicken embryo as a model organism. Sauka‐Spengler (WIMM)
Characterisation of key pathways involved in lipid metabolism and angiogenesis in Ovarian Cancer metastasis to the omentum. Harris (WIMM)
Characterisation of immune modulators of Ovarian Cancer cells in ascites fluid and omentum of patients with ovarian cancer. Cerundulo (WIMM)
Co‐supervised a CRUK Research Fellow, who is interrogating data from the “one million woman” study to identify epidemiological associations with Ovarian Cancer. Beral (Cancer Epidemiology Unit)
Characterizing the structural properties of key therapeutic protein targets in ovarian cancer (Stefan Knapp, Target Discovery Institute).
Developing novel mathematical models for studying genomic evolution in cancer (Chris Yau, WTCHG).

our collaborations with Oxford BRC Cancer and Surgery Themes

These collaborations enabled the establishment of:

An electronic database for integrating clinical information with operative videos in patients with Ovarian Cancer (OvaryWeb)
A pilot surgical study to evaluate a novel optical imaging device in sentinel lymph node detection in Ovarian Cancer (PIONIR study)
The Oxford Ovarian Cancer study to Predict Chemotherapy Response (OXO‐PCR) with Dr Shibani Nicum (Oncology)
The Gynaecological Oncology study for biomarker evaluation of novel therapeutic targets (GO‐Target) in Ovarian and endometrial cancers.

National Collaborations

We have strong collaboration with Martin Drysdale's laboratory at the Beatson Institute in Glasgow. Together we won a major grant from the Medical Research Council- Developmental Pathway Funding Scheme to develop novel therapies in Ovarian Cancer.

International Collaborations

We collaborate with Bob Bast's and Anil Sood's laboratories at the University of Texas, M.D. Anderson Cancer Center to characterize novel therapeutic targets in ovarian cancer. We collaborate with the Nathanael Gray's laboratory at Harvard to test novel therapeutic strategies in ovarian cancer. We are developing novel algorithms for the analysis of transcriptomes in ovarian cancer with Nuno Barbosa-Morais' laboratory at the Institute of Molecular Medicine in Lisbon, Portugal.

The Impact of our Work

Ahmed and colleagues discovered that almost all high‐grade serous ovarian cancers (HGSOCs) have mutations in the TP53 gene. Previously, it was thought that TP53 mutations only occurred in a fraction of HGSOCs: Hence, prior to Ahmed’s 2010 publication, researchers in the field focused on investigating the prognostic and predictive value of TP53 mutation in HGSOC. This finding meant that TP53 mutations in HGSOC have little prognostic or predictive value because they are ubiquitous. Instead, his observation established that HGSOCs are unified by the presence ofTP53 mutations, which has had a major impact on the molecular classification of epithelial Ovarian Cancer. It has also redirected research worldwide towards understanding why TP53 mutations are required in HGSOCs. This publication has been cited more than 200 times and several other groups, including The Cancer Genome Atlas (TCGA) Consortium, have confirmed the finding.