Breast Cancer Project

Features Projects
Principal Investigators: Dr Alberto Ocaña, Dr Atanasio Pandiella
Centres:  CHUA (University Hospital Complex of Albacete) – Albacete and CIC (Cancer Research Centre) – Salamanca

Background

Breast cancer is the most frequent type of cancer in women. It is estimated that one in 10 women may suffer from it sometime during their life. Although a large majority of breast cancer tumours are cured, even today 20% of patients are not. Resistance to treatment or the absence of specific therapies against certain types of breast cancer explains why certain tumours cannot be completely eliminated.

Project Description:

 

The breast cancer research projects headed by Atanasio Pandiella and Alberto Ocaña are focused mainly on two particularly aggressive types of breast cancer:

Triple -Negative Breast Tumours: Triple -negative breast cancer receives this name because the tumour cells lack certain molecules that define other types of breast cancer. These tumours have a very poor prognosis, and there is currently no specific therapy against them. Research in this field is therefore urgently required to develop effective therapies against these types of tumours.

Her2+ Breast Tumours: Her2+ breast cancers are very aggressive tumours, with cells presenting a large amount of the protein called Her2, which is the main reason for their transformation. Although there is a treatment against this type of tumours, a large number of patients develop a resistance to the treatments. This project is focused on finding out the mechanisms whereby the tumour cells avoid the treatment.

Advances made over the last year (2018-19):

Triple Negative Breast Tumours: Analysis of a huge volume of triple negative tumours has flagged several cell mechanisms that are altered in this type of tumour. One of these functions is the regulation of the cell cycle (in other words, when, how and under what circumstances a cell multiplies). On the basis of these findings, researchers have trialled in their lab, with great success, a combination of drugs that target some of these proteins together with other very novel compounds, known as BET inhibitors. The good data yielded by this research, published in the journal Oncotarget, are laying the foundations for a possible specific therapy that would be effective against these hard to treat tumours.

Her2+ Breast Tumours:

Our researchers are continuing to work on discovering why HER2+ breast cancer cells become resistant to the specific drugs developed for this type of pathology. These studies are generating a huge volume of results and feeding into several publications.

Two of the most important publications are related with a new drug called T-DM1. This is a very powerful treatment, but it does not always work. Our researchers have already identified two different mechanisms whereby tumour cells become resistant to these drugs. One of these mechanisms is related with the way the tumour cell traps and digests the drug  (published in Cancer Research), whilst the other is linked to the control of cell multiplication (published in Clinical Cancer Research). This might enable therapies to be used that neutralise these resistance mechanisms, thus favouring therapy based on T-DM1.

Trastuzumab is one of the classic treatments used against HER2+ tumours, but resistance also develops. Recently, a paper has been sent for publication in which the authors observe that when cells become resistant to this drug, the mechanisms that would cause them to die are altered. Furthermore, the results of a Phase II clinical trial have been published, demonstrating the effectiveness on patients of the combination of trastuzumab with another drug, dasatinib.

Immunotherapy Project for Triple Negative Breast Tumours:

The project has only recently been launched, but it is already advancing at great speed. Following an in-depth analysis of the proteins and genetic matter of triple negative tumour cells, 3 possible targets have been identified for antibodies loaded with drugs specifically designed to attack those cells. The team is currently developing a form of immunotherapy based on these data.

Achievements from pre 2018:

 

In Triple -Negative Breast Tumours: using bioinformatics tools, a large number of triple-negative tumours have been analysed, identifying a series of cellular functions specifically altered in these types of tumours. A panel of compounds specifically intervening on these functions of tumour cells is currently being tested, and could result in the development of new drugs in the future. Once it is established which compounds are the most effective, trials will be undertaken in animal models to continue assessing the effectiveness of possible treatments. As a result of this research, in January 2017 an article was published in the publication Oncotarget.

Her2+ Press Tumours: During the year, cell and animal cultures resistant to current treatments have been established. To date, results in cellular lines have allowed identifying interesting genetic programs and gene alterations in tumour cells that could explain resistance to currently drugs.