Understanding how BCL3 promotes homologous recombination in colorectal cancer cells

Background: Colorectal cancer (CRC) patients often present at clinic with advanced disease (where the tumour has spread) making it more difficult to treat.

Rectal cancer patients are treated with chemotherapy and radiotherapy (CRT) prior to surgery, although response is variable and patients who do not respond have a worse prognosis. The aim of this work is to improve the response of CRC patients to therapy.

Previous work from our laboratory suggests tumours with high levels of the BCL-3 protein are less responsive to CRT because BCL-3 promotes DNA damage repair, allowing the cancer cells to become resistant to DNA damaging therapy.

Approach: I aim to investigate how targeting BCL-3 levels inhibits DNA repair, leading to sensitization of cancer cells to therapy.

We will study the effect of BCL-3 on the density of DNA (which can modify repair processes), and identify which proteins interact with BCL-3 when DNA is damaged to understand the mechanism.

We will test the suitability of BCL-3 as a therapeutic target, using a small molecule BCL-3 inhibitor to treat colorectal cancer models.

Impact: This work will help us understand the link between BCL-3 and therapeutic resistance, and the validity of BCL-3 as a therapeutic target for CRC.