Marcus Skribek

Marcus Skribek

Affiliated to Research
Visiting address: J6:20 BioClinicum, Akademiska stråket 1, 17164 Solna
Postal address: K7 Onkologi-Patologi, K7 Forskning Ekman, 171 77 Stockholm
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About me

  • Primary research focus is on improving the efficacy of immune checkpoint inhibitors (ICI) through translational research in patients with advanced non-small cell lung cancer (NSCLC).

    Dual role as a clinician and researcher:

    • Clinical Oncologist at Theme Cancer, Karolinska University Hospital
    • Postdoctoral Fellow at the Department of Oncology-Pathology, Karolinska Institutet

     

    Treatment with ICIs demonstrate impressive responses and prolonged survival in a selected group of 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.

Research

  • 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.

    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

    • Seminar supervisor in cancer biology (/i.e./ targeted therapy), courses in oncology
    • Clinical supervisor for medical students
    • Supervisor in Ekman's lab (supervise medical students and clinical researchers)
    • Responsible for organizing educational seminars for residents in oncology
    • Created local guidelines for the use of hematopoietic stimulating factors in solid cancers.
    • Peer reviewer for several eminent international scientific journals.

     

    Memberships:

    • 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)

     

    Awards:

    • Cum Laude in Doctor of Medicine (M.D.)
    • Award for Outstanding Presentation

Articles

All other publications

Grants

  • Research Grant
    The Cancer Research Funds of Radiumhemmet
    1 June 2022 - 31 May 2024

Employments

  • Affiliated to Research, Department of Oncology-Pathology, Karolinska Institutet, 2023-2026

Visiting research fellowships

  • Clinical Research Fellow, Memorial Sloan Kettering Cancer Center, - Joined MSKCC to deepen expertise in oncology through firsthand learning of cancer management and treatment practices. - Collaborated with multidisciplinary teams to enhance patient outcomes and advance cancer care methodologies. - Specialized in radiotheranostics at the Jason Lewis Lab, integrating diagnostic imaging and targeted therapy to develop precision medicine approaches. - Involved in research focusing on DLL3 in small cell lung cancer and DLK1 in sarcoma, aiming to develop effective therapies for aggressive cancer types. - Worked under the supervision of industry-leading experts to pioneer novel cancer therapy methods., 2024-2024

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