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Our parity studies in mice revealed an anti-inflammatory protein is highly expressed in parous protected breasts. This protein is expressed in normal breast and lost in breast cancer. We used it to predict the outcome of early stage patients and showed it was safe and effective at inhibiting breast cancer in mice.

Here we will determine the best way to develop it into a breast cancer therapy. Chemotherapy is the mainstay of treatment for triple-negative breast cancer, an aggressive subtype of breast cancer.

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Unfortunately, the majority of triple-negative breast cancer patients do not respond adequately to chemotherapy and long-term prognosis for these patients is poor. We have identified a mechanism that limits the efficacy of chemotherapy for the treatment of triple-negative breast cancer. In this project, we will establish novel combination therapy strategies to improve survival outcomes for patients diagnosed with triple-negative breast cancer.

There is substantial variation in how well prostate cancer patients respond to the standard therapies of androgen deprivation and chemotherapy. Poorly responding tumours are often enriched in particularly aggressive cell types. Tumours containing such highly malignant cells will be grown in mice, to mimic the course of patient treatment.

We will use DNA sequencing to study in great molecular detail how these tumours change in response to therapy. This work will show how therapy resistance occurs, help identify resistant tumours and develop new first-line therapies for at-risk patients. This proposal will systematically determine how messenger RNA splicing and export, two coupled steps in the gene expression pathway, are altered in haematological malignancies, identifying potential therapeutic vulnerabilities. This will enable us to develop novel RNA processing based therapies to treat patients with mutations in RNA processing factors.

A new class of drugs called CDK inhibitors have shown promising results in the laboratory and in early clinical studies for patients with blood cancer. However, many patients eventually get relapsed disease and therefore new treatment strategies are needed. How these drugs work in cancer cells is not completely understood and this project will use new sequencing technologies to investigate how blood cancer cells respond to drugs that target a protein called CDK9.

It is expected that this study will identify strategies to enhance the effectiveness of CDK9 inhibitors and improve patient care. Chelsea Bennington. Justin Pangilinan. Jennifer King-Maury 12 Oct Jen Jen 11 Oct Ivica Sikiric. Nati Natasha S. Mary Curtin-Nowinski 07 Oct Brenda Montufar.

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