PhD project

Simone Stensgaard, MSc

Publications (link to AU profile)

My PhD project is focused on the detection of biomarkers in blood samples from lung cancer patients. Despite advancements in the treatment of lung cancer, it remains one of the leading cancers worldwide, both in terms of incidence and mortality. Most non-small cell lung cancer (NSCLC) patients have incurable advanced disease at the time of diagnosis. The developments in immunotherapy and targeted therapy have provided new hope for these patients. The application of blood-based biomarkers for determining response and survival may further improve the prognosis.

My PhD project is split into three studies: study I, study II, and study III, which focus on advanced NSCLC treated with immunotherapy or targeted therapy, respectively.

In study I the use of circulating tumor DNA (ctDNA) and immune-related plasma proteins as predictive biomarkers were investigated in NSCLC patients treated with immunotherapy. The expression of programmed cell death 1 ligand 1 (PD-L1) on tumor cells is used to determine eligibility for treatment with the checkpoint inhibitor pembrolizumab, which targets the programmed cell death protein 1 (PD-1). Although immunotherapy has improved survival for NSCLC patients, not all patients respond equally well to treatment. More knowledge is needed to identify patients who will benefit from treatment. Blood-based biomarkers may be a useful tool for this identification, both at determining eligibility for treatment, but also as a way of monitoring treatment response.

Study II addresses the use of ctDNA monitoring of EGFR-mutated NSCLC patients treated with the EGFR inhibitor osimertinib in a first-line setting. The study is currently ongoing and aims to include blood samples from 100 patients collected before the start of treatment, during the treatment period, and at progression. The purpose is to identify predictive biomarkers for response in ctDNA during the first few weeks of treatment and to investigate resistance mechanisms at progression.

Study III is focused on the detection of a novel biomarker – extrachromosomal circular DNA (eccDNA). The studies on ctDNA have mainly been focusing on linear fragments, but studies on tissue have demonstrated that DNA exist in a circular form residing outside of the chromosomes. In this study, the aim is to isolate eccDNA from plasma samples from patients with advanced NSCLC and contribute to enhancing the understanding of the cancer biology behind eccDNA. Furthermore, the value of eccDNA as a biomarker will be investigated to improve treatment selection and monitoring.

Monitoring of biomarkers in the blood is an informative and minimally invasive method of detecting predictive factors for response and survival. The data obtained so far show that ctDNA and immune-related plasma proteins hold the potential for identifying treatment responders from non-responders and ultimately, improving quality of life and survival.

This research has been supported by grants from:

• The Danish Cancer Society
• NEYE Fonden