With more than 3000 cases diagnosed annually in Sweden and an overall five-year survival rate of less than 15%, lung cancer is the leading cause of cancer death. Although cigarette smoking is the major etiological factor, the number of never-smokers diagnosed with lung cancer has increased continuously in recent years, especially among younger individuals. More than 20% of women and about 10% of men who develop lung cancer have never smoked.The diagnosis is often late and only about 25% of the tumors are accessible for surgery, which is a prerequisite for long-term survival. Improved tools for early diagnosis are therefore of great importance. The five-year survival after successful resection is approximately 30-60% with a 3-10% additional increase in survival rates if adjuvant chemotherapy is used. However, apart from tumor stage, no prognostic factor that sufficiently well predicts patient outcome has been identified. A major challenge is thus to identify patients at risk of metastatic relapse and develop tools to determine the likelihood for response to various therapies.
Lung tumorigenesis is a result of multiple genetic alterations and the tumors show a high frequency of acquired mutations, copy number alterations, epigenetic alterations and/or gene expression changes involving a large number of genes. Our research aims to improve the diagnostics, prognostics and therapeutics by a combined clinical and molecular approach. In close collaboration with thoracic surgeons and pathologists, we collect tumor biopsies, normal lung tissue and blood samples from all patients undergoing primary lung cancer surgery in the southern Swedish health care region in order to establish a biobank for both discovery and validation (The Southern Swedish Lung Cancer Study). In order to identify critical events for tumor initiation and progression, we use both focused techniques, such as immunohistochemistry and digital PCR, and genome-wide techniques including different microarray-based applications and rapidly evolving next-generation sequencing techniques for profiling of differences in transcription, epigenetic modifications, DNA copy number, mutations and structural rearrangements in and between clinical specimens. Data and results from these genome-wide techniques are correlated with clinical information such as histology, prognosis and smoking status in order to discover patterns of genomic alterations in tumors that may delineate novel subgroups, refine prognosis, identify additional targets for synergistic treatment, and provide new insights into resistance mechanisms and molecular pathogenesis in lung cancer subgroups. We are also initiating blood-based screening of mutations and tumor specific rearrangements from circulating tumor DNA with the aim to facilitate earlier diagnosis and monitoring of treatment response based on multiple sampling during treatment.
The Southern Swedish Lung Cancer Study
Created in 2005, the Southern Swedish Lung Cancer Study is a multidisciplinary biobank initiative for molecular studies of lung cancer, with the long term goal of improving diagnostics, prognostics and therapeutics. We prospectively collect blood samples, fresh-frozen tumor biopsies and normal lung tissue from patients undergoing surgery for suspected or pre-operatively confirmed lung cancer (about 150 patients per year at the Department of Thoracic Surgery, Skane University Hospital, Lund). The Southern Swedish Lung Cancer Study thus harbours thoroughly reviewed primary lung cancer cases with complete clinically relevant data, including information on smoking history, histological subtype, TNM-status, oncological therapy, cancer recurrence, and overall and disease specific survival. The project has approval from the Ethics review board at Lund University.
Our research is performed in an open environment with close cooperation with other research groups within the Canceromics Branch and Division of Oncology, as well as with clinical oncologists, surgeons and pathologists.
LUCAS (The Lung Cancer Study in Southern Sweden)
For our long-term goal of improving diagnostics, prognostics and therapeutics, multidisciplinary biobank initiatives are essential. Since 2005, we prospectively collect blood samples, fresh-frozen tumor biopsies and normal lung tissue from patients undergoing surgery for lung cancer (about 150 patients per year at the Department of Thoracic Surgery, Skane University Hospital, Lund). The Southern Swedish Lung Cancer Study (Södra Lungcancerstudien 2005-2014), thus harbors thoroughly reviewed primary lung cancer cases with complete clinically relevant data, including information on smoking history, histological subtype, TNM-status, oncological therapy, cancer recurrence, and overall and disease specific survival. In 2014, we extended and renamed the project; The Lung cancer Study in Southern Sweden (LUCAS) also includes lung cancer patients with in-operable (locally advanced or disseminated) disease and, importantly, we also collect repeated blood samples longitudinally during treatment and follow-up, enabling subsequent ctDNA analysis and assessment of other blood based markers (e.g. tumor serum markers). So far, >1000 unique patients are included. The collection is supported by the Regional Cancer Center (RCC Syd) and the departments of Respiratory medicine, Thoracic surgery, Pathology and Clinical chemistry and now forms the backbone of the Southern Swedish PPMC node (Partnership for Precision Medicine in Cancer, supported by the Sjöberg foundation). Our research is performed in an open environment with close cooperation with other research groups, within the Canceromics Branch and Division of Oncology as well as with clinicians and researchers regionally and nationally.
SMIL (Swedish Molecular Initiative against Lung cancer)
The Swedish molecular initiative against lung cancer (SMIL) constitutes a national collaborative group, involving oncologists, pulmonologists, pathologists, surgeons, radiologists and molecular biologists with a concerted competence within the field of molecular cancer research and a special interest in lung cancer. In an ongoing project, we aim to characterize a nation-wide, population-based and clinically well-described lung tumor cohort of never-smokers. From the National Lung Cancer Registry (NLCR), we identified 540 cases of never-smokers who underwent surgery for lung cancer during 2005-2014 in any of the six health care regions (Regional Cancer Centers) of Sweden. Histopathological and clinical data has been re-examined, DNA and RNA collected, and tissue microarrays constructed. By applying modern high-throughput molecular techniques on a clinically very well characterized and nationwide, population-based, tumor material, our studies will now add valuable information on the tumorigenic mechanisms behind smoking-independent lung cancer and perhaps lead to new views on the diagnostic needs, prevention measures and to new treatment strategies for this group of patients. The project also forms the basis for register-based investigations of potential risk exposures, which will further clarify mechanisms behind lung cancer in never-smokers.