Evaluating Photodynamic Therapy in colorectal cancer using patient-derived organoids

About the Project

Colorectal cancer (CRC) is the 3rd most common cancer worldwide. Surgery is first line treatment and often in adjunct with chemotherapy. However, up to 20% of patients develop recurrent disease after treatment. Photodynamic Therapy (PDT) is an emerging anti-cancer treatment method, which can substantially improve the outcomes of treatment in CRC. PDT involves the administration of a photosensitising agent to cancers, followed by the irradiation of light to the cancer growth. This results in the activation of the photosensitising agent, eliciting cell death through the generation of reactive oxygen species and oxidative stress. This project will involve the investigation of PDT in CRC using different in vitro models of CRC. Recently, it has been identified that 2D cell cultures are not adequate and efficient in providing reliable and clinically representative outcomes of treatment. This is due to the limited capacity and application of 2D cell cultures and their lack of representation of clinical cancers. 3D spheroidal cell cultures and more recently, patient-derived organoids have been identified as vastly more improved and better models of CRC to pre-clinically evaluate treatments.

In this project, PDT will be evaluated in simple 2D monolayer and more advanced 3D spheroidal cell monocultures and co-cultures of CRC. In our laboratory, we culture patient-derived organoids, directly from CRC patients in Leeds and will be used in this PhD project to study PDT treatments. The candidate will liaise with the colorectal surgery team at St James Hospital to collect and process CRC tissue specimens from theatre into organoids. Organoids will be subjected to PDT and other cancer treatments and interrogated on a molecular level to identify novel markers of chemoresistance.

Methods: Cell line and tissue culturing, patient-derived organoid culturing, cell viability assays, fluorescent microscopy, immunofluorescence, immunohistochemistry, western blotting, RT-PCR, single cell analyses, statistical analyses