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(MCRC Non-Clinical) Liquid biopsies to optimise immunotherapy for small cell lung cancer patients

Project Description

Project summary:
Small Cell Lung Cancer (SCLC) is the most aggressive form of lung cancer and prognosis is dismal, with <10% patients (pts) surviving beyond 2 years. Chemo- and radiotherapy are the mainstays of treatment, initially with high response rates but for most pts the disease returns with acquired resistance over several months and is lethal.

Immunotherapy (IoT) is transforming the treatment of many cancers. In SCLC, trials of inhibitors of the programmed cell death protein 1 (PD1) immune checkpoint (IC) are ongoing and reporting modest clinical benefit. However, although recent approvals for IC inhibitors nivolumab, pembrolizumab and atezolizumab in SCLC are encouraging, IoT brings significant financial cost and toxicity and there is an urgent need to personalise therapy, by developing biomarkers to guide selection of pts most likely to benefit and detect relapse early.

Collection of tumour biopsies is challenging in SCLC but liquid biopsies offer a less invasive alternative to predict and track response to therapy. SCLC pts have a high level of circulating tumour cells (CTCs) and circulating tumour DNA (ctDNA), measurable in a simple blood sample that can be taken repeatedly and these are yielding promising data with which to assess SCLC biology at diagnosis and throughout the disease course and inform pt treatment. ctDNA can be used to measure tumour mutation burden and alterations in DNA-damage response genes associated with response to IoT. Peripheral immune cell subsets and the T-cell receptor repertoire have also been associated with response to IoT in some cancers. The overall goal of this project is to develop biomarkers measurable in a non-invasive liquid biopsy that personalises the use of IoT for SCLC pts by guiding therapy selection, improving clinical management and ultimately pt outcomes.

Entry Requirements:
Candidates must hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage. Applications from all nationalities are welcome.

Funding Notes

The Studentship will cover an annual stipend (currently at £19,000 per annum), running expenses and PhD tuition fees at UK/EU rates. Where international student fees are payable, please provide evidence within your application of how the shortfall will be covered (approximately £19,000 per annum).

The length of this project will be FOUR YEARS.

Related Subjects

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