Marcus Skribek

Marcus Skribek

PhD Student

Primary research focus is on improving the efficacy of immune checkpoint inhibitors through translational research in patients with metastasized non-small cell lung cancer.

About me

Dual role as a clinician and researcher:

  • Resident Oncologist at Theme Cancer, Karolinska University Hospital
  • PhD Student at the Department of Oncology-Pathology, Karolinska Institutet

Treatment with immune checkpoint inhibitors (ICIs) demonstrate impressive responses and prolonged survival in a selected group of non-small cell lung cancer (NSCLC) patients, but treatment resistance is still a major clinical challenge shortening patient survival.

My research aims to identify potential clinical factors and biomarkers for treatment response and resistance. Such findings can improve survival and quality-of-life in this patient group and may also lead to novel concepts of therapy.

Memberships:

  • Medicinska Föreningen (MF)
  • International Association for the Study of Lung Cancer (IASLC)
  • Swedish Society of Oncology (SOF)
  • European Society for Medical Oncology (ESMO)
  • American Society of Clinical Oncology (ASCO)

Volunteer:

  • Medical Aid & Teaching in Ghana

Research description

Lung cancer is the leading cause of death amongst both men and women worldwide; it causes approximately 23% cancer-related deaths in both genders. Lung cancer is typically diagnosed at an advanced stage when distant metastases are already present. Nonetheless, there has been a steady decline in lung cancer-related deaths, in part due to novel therapies such as ICIs, yet prognosis remains poor with approximately 13% five-year survival rates.

Advances in tumor biology and diagnostic methods for the identification of essential druggable aberrations in the tumors, such as mutations, rearrangements and protein overexpression, have led to the development of several therapeutic alternatives, including ICIs. One known hallmark of cancer is the evasion of the host's immune system, which enables tumor proliferation and progression. NSCLC in particular has been studied judiciously in this area. Recent discoveries have suggested that NSCLC has a high mutational burden, which suggests the existence of neoantigens and its potential immunogenicity. As a result, the development of ICIs has cemented a new area of cancer treatment.

The PD-L1 inhibitor pembrolizumab is approved in the first-line setting in patients with advanced NSCLC with a high PD-L1 expression due to better survival outcomes when compared to standard chemotherapy. Nevertheless, only a small (albeit significant) proportion of patients with ongoing ICIs experience durable remission. Studies have indicated that PD-L1 expression plays a vital role in clinical response to ICIs; a higher PD-L1 expression (≥50%) leads to a better clinical outcome than low PD-L1 expression (≥1%) in terms of overall response rate and overall survival. However, the role of PD-L1 as a predictive biomarker remains a topic of debate as low or negative PD-L1 expression levels have also shown clinical response to ICIs with tolerable side-effects. Other potential biomarkers are still under investigation (i.e. tumor mutational burden).

The presence of brain metastases (BM) in NSCLC patients is an adverse prognostic factor, with increased incidence in adenocarcinoma and tumors harboring oncogenic driver mutations. Approximately 25% of NSCLC patients present with BM at diagnosis. Survival outcomes after standard doublet chemotherapy administration with a platinum backbone have been modest, with real world data demonstrating OS ranging from 5.6 months to 9.3 months in patients with BM. However, the use of ICIs in NSCLC patients with BM is a matter of ongoing debate due to the scarcity of available data and the concerns about ICI efficacy in the context of the divergent tumour microenviroment in the CNS.

Therefore, there is a clear need to further investigate the effects of ICIs at both the molecular level as well as in the clinical setting to improve our understanding in this area.

Teaching portfolio

  • Seminar supervisor in cancer biology (i.e. targeted therapy), courses in oncology
  • Clinical supervisor for medical students
  • Junior supervisor in Ekman's research group
  • Responsible for organizing educational seminars for residents in oncology

Education

Doctor of Medicine (M.D.), Semmelweis University, Faculty of Medicine - Cum Laude

Doctor of Philosophy (Ph.D.), Karolinska Institutet - Ongoing

  • Research School for Clinicians in Epidemiology - Ongoing

Elective clinical placements (2013-2018):

  • Karolinska University Hospital, Stockholm - Medical Oncology
  • Prince of Wales Hospital, University of New South Wales, Sydney - Surgical Oncology, Vascular Surgery, and Traumatology
  • The Royal Infirmary, University of Edinburgh, Edinburgh - Orthopaedic Surgery
  • Semmelweis University, Budapest - Endocrinology, Obstetrics & Gynecology
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