In the last 40 years, the life expectancy of women with endometrial cancer has not been extended. The therapeutic options to treat this cancer are limited, and when a patient stops responding to the main treatment there are very few alternatives to fight the cancer.
Now, a team of researchers from the Bellvitge Biomedical Research Institute (IDIBELL) in Hospitalet de Llobregat, Barcelona; the Catalan Institute of Oncology (ICO) and the Bellvitge University Hospital (HUB) in Hospitalet de Llobregat, has generated a mouse model capable of faithfully mimicking human endometrial tumors. This new model, which is generated from a biopsy of the original tumor, can be the basis for research into new treatments and, more importantly, allow each tumor to be studied individually to define the best treatment for each patient.
Dr. David Llobet-Navas, principal investigator at IDIBELL and one of the three project leaders, explains: “This new model will allow us to study in real time what is the best therapeutic option for that specific patient and advance the evolution of the disease, and thus be more effective and avoid unwanted side effects.”
To generate the model, the team led by Laura Devis-Jauregui, from IDIBELL, implanted a biopsy of the human tumor in the same mouse tissue in mice. In total, in this project, 15 mice with 15 different human endometrial tumors have been studied.
After implanting the tumors into the mice, allowing them to evolve for approximately 100 days, the researchers determined that the implants maintain the molecular and morphological characteristics of the original tumors, making them a great model for research.
“Cancer is not a homogeneous disease, on the contrary, each case is different and there are many factors involved, not only genetic, but also the environment in which the tumor is found. That is why this model is so useful to us, since it reproduces the behavior of a human tumor in its environment”, says Dr. Alberto Villanueva, also project leader, and head of the research group at IDIBELL and the Catalan Institute of Oncology.
Members of the research team. (Photo: IDIBELL)
Between 15 and 20% of patients with endometrial cancer develop resistance to treatment, which is a big problem when there are no effective therapeutic alternatives. Consequently, the life expectancy of these women is less than one year.
In this study, thanks to the new model, it has been verified that tumors that present a specific mutation in the HER2 gene are sensitive to a drug called trastuzumab. In previous studies and clinical trials currently underway, the possible effectiveness of this compound had already been pointed out in a small percentage of patients with endometrial carcinoma. This study opens the range of therapeutic opportunity to more patients.
“We have generated a model that can boost endometrial cancer research, especially the exploration of new therapeutic pathways, since we have verified that we can reproduce genetic profiles in tumors that reveal unexpected vulnerabilities”, says Dr. Xavier Matias-Guiu , head of the IDIBELL gynecological cancer research group and Head of the HUB’s Pathological Anatomy Service.
El estudio se titula “Generation and Integrated Analysis of Advanced Patient-Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer”. Y se ha publicado en la revista académica Advanced Science. (Fuente: IDIBELL)