Inhibiting the protein Galectin-1 (Gal1) could become the first effective treatment for slowing the progression of the most common type of pancreas cancer, pancreatic ductal adenocarcinoma, for which, at present, there is no type of curative treatment available.
This type represents 85% of the pancreatic cancer cases diagnosed and, despite its prevalence being only 3%, it is fourth in the number of deaths related with this disease. The low survival rates are caused by the fact that there is no way of diagnosing it early, because symptoms are mild and, when they are detected, the cancer is often at advanced stages, combined with the fact that it does not respond to conventional treatments.
Inhibiting this protein lengthens lifespan in animals; their tumours progress more slowly, are less aggressive and have lower metastasis rates
Four routes of approach
Ductal tumours of the pancreas develop within a particular tumoral micro-environment, which is considered one of the keys for understanding their development and their resistance to conventional chemotherapies, as well as the lack of success of new treatments, such as immunotherapy. Within this environment, which is favourable to tumour cells and which isolates them from the immune system and from treatments, there are some cells called fibroblasts which are responsible for the production of large quantities of Galectin-1. This protein plays a vital role in the entire process of the tumour’s growth. It increases its proliferation, migration and invasion, in other words, it makes it more aggressive. It also plays a key role in the creation of an environment favourable to its growth and, at the same time, it keeps the immune system depressed, which enables the tumour to remain invisible.
Faced with the complexity of tackling these kinds of tumour, researchers have worked with four different approaches to try to reconstruct the final puzzle presented by the role of Gal1 in pancreatic cancer. Studies have been conducted in vivo, with a transgenic model in mice to see how the inhibition of this protein affects tumour development, and also three other strategies with human cells: in vitro, in vivo, with mouse models, and large-scale molecular genomic studies.
Inhibiting Gal1, a pathway for treating pancreatic cancer
The results obtained indicate that inhibition of Gal1 slows down tumour growth and re-establishes the vigilance of our immune system to recognise and reject tumour cells, which makes it difficult for the tumour to continue progressing. In this sense, the researchers indicate that “when Gal1 is eliminated from the tumours, the animals live for a longer time because the tumours progress more slowly, are less aggressive and have lower metastasis rates”. However, this is a pre-clinical study with animals and new studies need to be carried out to validate the inhibition of Gal1 as a therapeutic alternative in humans.
Orozco CA, Martínez-Bosch N, Guerrero PE, Vinaixa J, Dalotto-Moreno T, Iglesias M, Moreno M, Djurec M, Poirier F, Gabius HJ, Fernández-Zapico ME, Hwang RF, Guerra C, Rabinovich GA, Navarro P. Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor–stroma crosstalk. PNAS April 3, 2018; 1165(16): E3769-E3778.