Pancreatic cancer is one of the most aggressive and highly deadly malignancies in existence. In Spain, more than 10,000 people are diagnosed each year, of which less than 10% survive more than five years after diagnosis. The problem is aggravated by the fact that it is a tumour that is difficult to diagnose in the early stages, when the chances of curing it are greater, since it does not cause symptoms until it has spread to other organs. In addition, an already complicated situation is compounded by a common resistance to conventional treatments.
In this hopeless context, studies such as the one recently published in the Journal of Experimental & Clinical Cancer Research give the necessary impetus to continue researching in the search for effective therapies that can increase patient survival.
The research has been co-led by the group of Dr. Atanasio Pandiella, principal investigator of the Cancer Research Center (CSIC-University of Salamanca) and CRIS Against Cancer, and the team of Dr. Gabriel Capellá, leader of the Hereditary Cancer research group and director of IDIBELL, as well as CIBERONC researcher. The synergy between the IDIBELL and CSIC teams has been key and is another example that scientific excellence and translational research in oncology are achieved collectively.
An innovative approach: guided missiles against cancer
The teams of Dr. Pandiella and Dr. Capellá have opted for the use of antibodies conjugated to cytotoxic drugs as a therapeutic strategy. These antibodies are a kind of guided missiles with the ability to selectively recognize molecules present in cancer cells and, in doing so, release the drugs that cause their death. Most importantly, they can do so in such a targeted way that they don’t damage surrounding healthy cells.
This strategy has been used in cancer research for some time, but, as Dr. Pandiella points out, it is a new field in the study of pancreatic cancer: “Antibodies conjugated to cytotoxic drugs have already demonstrated their efficacy in other types of tumors, with more than 200 clinical trials underway internationally. but until now, pancreatic cancer did not have such a strategy.”
Molecular architecture: the parts of the missile
To design this strategy, the researchers identified the TGFα protein as a therapeutic target in pancreatic cancer. Thanks to the analysis of samples from patients with this type of cancer, they saw that TGFα, essential for cell proliferation, was overexpressed in tumour samples compared to healthy ones and, in addition, that the elimination of its activity drastically reduced tumour proliferation. Thus, TGFα became the perfect molecular clue to reveal the presence of pancreatic cancer and, therefore, the weak point through which to attack pancreatic tumour cells.
On this basis, several monoclonal antibodies were developed capable of identifying TGFα and conjugates in different cytotoxic drugs, already used in the clinic, to be able to act against cancer once it has been recognized. Of all the combinations generated, two were selected for their specificity and effectiveness: what would be the guided missiles, 5F1 and 16B10.
And they worked: according to the results in animal models and cell cultures, the missiles managed to slow down and even induce tumor regression with minimal adverse effects.
Implications for the future
The results achieved represent a key advance in the development of new precision treatments against pancreatic cancer. The specificity of the treatment allows for selective targeting of tumor cells, minimizing damage to healthy tissue and potentially reducing side effects associated with conventional chemotherapy.
In addition, the study demonstrates, for the first time, the feasibility of using TGFα as a tumour target in therapies of this type. Thus, given that this molecule is also very present in other aggressive cancers, such as lung cancer, it opens the door to future applications in other tumors that are difficult to treat.
The Bellvitge Biomedical Research Institute (IDIBELL) is a research centre created in 2004 and specialising in cancer, neuroscience, translational medicine and regenerative medicine. It has a team of more than 1,500 professionals who, from 73 research groups, publish more than 1,400 scientific articles a year. L’IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Health Institute, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus d’Excelencia Internacional of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centres accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the HR Excellence in Research program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Centre of the AECC Scientific Foundation (FCAECC).