- Pancreatic cancer is one of the most aggressive forms of cancer as well as one of the least responsive to treatment
- An existing targeted anticancer therapy currently used to treat some leukemias and lymphomas may also be effective against pancreatic cancer
Barcelona, April 15, 2015. – Researchers from VHIO´s Mouse Models of Cancer Therapies Group have demonstrated the efficacy of a BTK inhibitor for the treatment of pancreatic cancer in preclinical mouse models. Ibrutinib, a targeted therapy already used to treat some leukemias and lymphomas, could also prove effective in the treatment of pancreatic cancer. The results of this preclinical study led by Laura Soucek and published in the journal Cancer Research, propose a new use for ibrutinib that could also open up novel therapeutic avenues for other fibrotic diseases.
Over the last few years Soucek´s lab has focused on the importance of mast cells in certain tumor types. Ibrutinib is a small-molecule BTK (Bruton’s tyrosine kinase) inhibitor that is both essential for the maturation of B cells implicated in some hematological cancers as well as vital for mast-cell activation. These considerations led the group to test the mast cell-inhibiting properties of this drug for the first time in an insulinoma mouse model. The results proved encouraging – so much so that they decided to further test the drug in models of pancreatic adenocarcinoma; the most common and aggressive pancreatic tumors exhibiting significant mast-cell infiltration and rapid cancer growth and spread. Patients with this disease are largely unresponsive to treatment and the survival rate is consequently low.
The findings were conclusive and tumor growth in mice decelerated. Ibrutinib was tested as both a monotherapy and in combination with gemcitabine (standard chemotherapy cancer of the pancreas), resulting in improved survival in mice, in both scenarios.
Commenting on the complexities of treating pancreatic Daniel Massó, Graduate Student of Laura´s group and first author of the paper explains, “Pancreatic tumors are found interspersed in dense fibroinflammatory stroma. A sort of ball of fibroblasts and collagen acts like a ´defense´ capsule which makes it difficult for chemotherapeutic agents to effectively reach the heart of the tumor”. This study has shown that ibrutinib clearly reduces this stroma, and as Daniel Massó observes, “our hypothesis is that this is one of the mechanisms which, together with standard chemotherapy, will improve survival.” Ibrutinib weakens the capsule and therefore might improve gemcitabine effectiveness.
A potential therapeutic avenue for pancreatic cancer
Although these results are reported at preclinical level using experimental models, given the aggressive nature of pancreatic tumor, the lack of therapeutic options available, and factoring in that the drug has already been approved and used to treat other cancers, next steps in establishing the use of ibrutinib for pancreatic cancer should be accelerated. “It usually takes several years for scientific discovery to enter clinical practice. In this instance, since the efficacy and safety of this agent in the clinic has been previously established and it has already been approved for some types of cancer, we can reasonably hope for the fast-track set up of a clinical trial aimed at validating the use of ibrutinib against pancreatic cancer”, observes Laura Soucek, Principal Investigator of VHIO´s Mouse Models of Cancer Therapies Group.
These findings also facilitate future studies aimed at establishing ibrutinib as a potential therapeutic option for fibrotic diseases, such as pancreatitis or hepatic fibrosis, for example.
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For more information please contact: Amanda Wren, Director of Communication,
Vall d´Hebron Institute of Oncology (VHIO), Tel: +34 695207886, Email: awren@vhio.net
