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27/01/2022 - Press release

New diagnostic marker for pancreatic cancer identified

• This is a new valid marker for diagnosing this type of tumour, one of the cancers with the worst prognosis. It is, in fact, the third leading cause of cancer death in developed countries.
• The study, published in the journal eBioMedicine, was led by researchers from the Hospital del Mar Medical Research Institute and IBB-CSIC-IDIBAPS. Their results point to a protein present in tumour cells as an indicator of pancreatic cancer in early stages of the disease
• This marker can be detected through a simple blood test, facilitating its application in clinical practice

A team of researchers from the Hospital del Mar Medical Research Institute (IMIM-Hospital del Mar) and IIBB-CSIC-IDIBAPS have identified a new viable early diagnostic marker for the most common type of pancreatic cancer, pancreatic ductal adenocarcinoma. The study has been published in the journal eBioMedicine, from The Lancet group, and may represent an important step in the early detection and treatment of this type of tumour, with one of the worst prognoses. Doctors and researchers from the Digestology and Medical Oncology Departments at Hospital del Mar, as well as from the Spanish National Cancer Research Centre (Centro Nacional de Investigaciones Oncológicas; CNIO), the Ramón y Cajal Institute for Health Research (Instituto Ramón y Cajal de Investigación Sanitaria; IRYCIS) and CIBER also collaborated in the study.

The study analysed the usefulness of the AXL receptor tyrosine kinase, a protein present on the surface of cells, to detect the presence of pancreatic cancer in patients. This protein is usually absent in normal cells, but it has been shown that its presence is significantly increased in certain types of tumours, such as in the pancreas, where it is related to disease progression, promoting tumour cell growth, migration and invasion, as well as regulating the immune response. The researchers sought to demonstrate whether its presence in blood could be detected and used for the early diagnosis of pancreatic cancer.

Pancreatic cancer, and specifically pancreatic ductal adenocarcinoma, actually has one of the worst prognoses of any tumour. It is the third leading cause of cancer death in developed countries, with almost 8,700 cases diagnosed in Spain in 2021. The lack of diagnostic markers is the main issue in tackling this cancer, as only 20% of patients can be operated on in time. This facilitates metastasis and treatment resistance in the most advanced tumours.

Research team

Confirmed using two patient cohorts

To demonstrate the usefulness of this marker, blood samples were collected and analysed from 59 patients at Hospital del Mar, the results being validated with a second group of 142 patients from Hospital Clínic in Barcelona. The study was complemented by a third cohort of familial pancreatic cancer patients, several animal models in mice, and corroborated using analyses of human tumour cells in vitro. "Levels of soluble AXL protein in blood were identified by collecting plasma and analysing the levels of this marker in the control group, in patients suffering chronic pancreatitis and those with pancreatic tumours. The cooperation of all the patients and their families is the key to a study like this one", explains Dr. Neus Martínez-Bosch, a researcher in the New Molecular Targets in Cancer Research Group at IMIM-Hospital del Mar and first author of the study.

"This demonstrated that the blood marker was only present in patients who had already developed the tumour, and not in healthy individuals or those suffering from chronic pancreatitis", adds Helena Cristóbal, a researcher at the IIBB-CSIC -IDIBAPS and co-first author of the study. Along the same lines, Dr. Luis Barranco, head of the Digestive Endoscopy section of the Digestive System Department at Hospital del Mar, points out that "This is very important because pancreatitis is a pathology that can make diagnosis difficult in patients with pancreatic cancer." Detection can be carried out through a simple blood test.

In view of the results, Dr. Pilar Navarro, coordinator of the New Molecular Targets in Cancer Research Group at the IMIM-Hospital del Mar and joint principal investigator of the study, explains that "The AXL protein is a specific marker that tells us that malignant cells are already present. This is an important finding, because sometimes tumour markers may appear in pre-neoplastic lesions, but these lesions do not necessarily progress in all cases. The fact that this marker is linked to the tumour-stage cell makes its specificity for diagnosing pancreatic cancer very important." The next step for the researchers is to initiate a multicentre study to analyse data from a large group of patients, validate their discovery and translate it into clinical practice.

Diagnostic application

Currently, there is no biomarker for the early diagnosis of pancreatic cancer. "The CA19-9 protein is used to assess treatment response in patients with elevated CA19-9 at the onset of the disease, but it cannot be used for diagnosis due to its low specificity. The availability of a new diagnostic tool is therefore of particular importance. Especially considering that early diagnosis is essential for tumour surgery, the only curative treatment option", stresses Dr. Laura Visa, a consultant in the Hospital del Mar's Medical Oncology Service.

The researchers also want to determine which patients can benefit from this new marker, as a small number of pancreatic tumours do not express the AXL protein. However, if the test is combined with the other existing marker, CA19-9, its ability to determine the presence of cancer cells increases, reaching a sensitivity of 90%. "We are very interested in learning why some cancers do not express AXL; this could give us clues as to how tumour mechanisms work that we could use as treatment targets", says Dr Pablo Garcia de Frutos, joint principal investigator of the study and head of the Cell Death and Proliferation Department at the IIBB-CSIC-IDIBAPS.

Precision diagnosis, personalised medicine and cutting-edge cancer research at Hospital del Mar

At Hospital del Mar, cancer is addressed through the diagnostic tools necessary to achieve a precision diagnosis that makes it possible to plan and offer patients personalised and individualised therapeutic options according to their particular circumstances. At the same time, there is a commitment to a patient-centred care model through pioneering and benchmark work in multidisciplinary functional units specific to each type of tumour.  The units, comprising professionals specialising in each cancer type, offer the best therapeutic options in a model of shared decision-making with the patient. Nurse managers guide patients through the diagnostic and therapeutic process. This quality care is combined with ground-breaking cancer research at the Hospital del Mar Medical Research Institute (IMIM) and an extensive programme of clinical trials. The research areas focus on furthering immunotherapy and liquid biopsy, searching for biomarkers and new therapeutic targets, and developing new surgery and radiotherapy strategies to improve efficacy and the quality of life of patients. This research generates almost 200 articles in scientific publications each year, two out of three of which are in high-impact journals. This state-of-the-art care and research are the basis for teaching excellence at the Hospital del Mar Campus.

Reference article

Neus Martínez-Bosch*, Helena Cristóbal*, Mar Iglesias, Meritxell Gironella, Luis Barranco, Laura Visa, Domenico Calafato, Silvia Jiménez-Parrado, Julie Earl, Alfredo Carrato, Noemí Manero-Rupérez, Mireia Moreno, Albert Morales, Carmen Guerra, Pilar Navarro*, Pablo García de Frutos*,

Soluble AXL is a novel blood marker for early detection of pancreatic ductal adenocarcinoma and differential diagnosis from chronic pancreatitis, eBioMedicine, Volume 75, 2022, 103797, ISSN 2352-3964, https://doi.org/10.1016/j.ebiom.2021.103797.

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