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HEStaff exchange2023–2027

BIOSMALL · Identification of subtype-specific biomarkers in small cell lung cancer

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-10-01 → 2027-09-30
EU contribution
€897,000
Participants
7
Scheme
HORIZON-TMA-MSCA-SE

Lines connect the coordinator with its partners.

Results in brief

Identification of subtype-specific biomarkers in small cell lung cancer

Lung cancer is one of the most frequently diagnosed malignancy worldwide and the leading cause of cancer-related mortality. Historically lung cancer is divided into two major categories: non-small-cell lung cancer (NSCLC, ~85%) and small-cell lung cancer (SCLC, ~15%). SCLC is infamous within the field of oncology for being among the deadliest cancers. This is due to its ability to rapidly develop resistance against current “gold standard” treatment strategies and extensively give rise to organ metastases. With more than 200.000 deaths worldwide each year it represents a major health issue and a great socioeconomic and humanistic burden. Clinically, SCLC is still regarded as a ‘homogenous’ disease, without significant therapeutic- and survival improvements in the last three decades. However, recently, there has been a worldwide resurgence of studies on SCLC, with the identification of distinct molecular subtypes. In the proposed study, our multidisciplinary team aims to deepen our understanding of the clinical significance of molecular subtypes in SCLC. Specifically, we aim to identify novel potentially targetable proteins and signaling pathways, to determine the genetic mutation landscape of SCLC, to reveal the efficacy of chemotherapeutic and targeted agents, to gain insights into the specific metastatic patterns of each subtype and to establish diagnostic/predictive/prognostic biomarker panels. Our project might help to focus and accelerate SCLC research and thus improve the clinical management of this devastating disease.

Data: CORDIS, © European Union

Project objective

Although small cell lung cancer (SCLC) is a particularly aggressive disease, targeted therapies have remained largely unsuccessful and there were no major therapeutic advances in the last three decades. In the clinics, SCLC is still treated as a molecularly homogeneous malignancy. However, recent analyses led to the classification of neuroendocrine and molecular subtypes, defined by differential expression of four key transcription regulators: ASCL1, NEUROD1, POU2F3 and YAP1. Our study proposal aims to identify unique subtype-specific diagnostic and therapeutic biomarkers for SCLC patients with state-of-the-art multiomic approaches, and moreover to deepen our understanding of the biological and clinical significance of SCLC molecular subtypes. We intend to investigate the diagnostic and therapeutic significance of each subtype in a large panel of human SCLC cell lines in correlation with their proteomic and metabolomic profiles, in vivo metastatic capacity and sensitivity to potential targeted agents. Additionally, the specific features of the molecular subtypes will be also assessed by performing genetic mutation analyses and using in-depth machine-learning algorithms. All potential circulating biomarkers delineated by proteomics and metabolomics will be first validated by a series of in vivo experiments in different murine models. In addition, in order to improve patient selection and follow-up in a non-invasive manner, the specific PET-CT radiomic features of enrolled patients will be also analysed within the framework of the current study. Altogether, by identifying a wide range of novel biomarkers and potential therapeutic targets via multiomic approaches, the current study will possibly result in a new subtype-specific biomarker panel which will contribute to the development of individualized diagnostic and/or therapeutic strategies in this hard-to-treat disease.

Original text from CORDIS.

Participants

  • MEDIZINISCHE UNIVERSITAET WIEN · WienCoordinatorAustria
  • KINETO LAB. KUTATAS-FEJLESZTESI ES TANACSADO KFT · BudapestHungary
  • LUNDS UNIVERSITET · LundSweden
  • ORSZAGOS KORANYI PULMONOLOGIAI INTEZET · BudapestHungary
  • RIJKSUNIVERSITEIT GRONINGEN · GroningenNetherlands
  • TREAT4LIFE AB · MALMOSweden
  • UNIVERSITAETSKLINIKUM ESSEN · EssenGermany

Links

Data: CORDIS, © European Union