New therapeutic target cell against breast cancer
José Pichel Andrés/DICYT Scientists of Cancer Research Center of Salamanca have identified the protein R-Ras2, also known as TC21, as a therapeutic target cell against breast cancer, that is, a molecule on which, in theory, drugs to combat this illness can act. After five years of work, the researchers of this center, a mix of CSIC and the University of Salamanca, have verified that while eliminating this protein in lab rats, the growth of primary tumors has stopped and lung metastasis has been avoided. This work has been published today at the renowned scientific magazine Nature Communications.
“We wished to know if inhibiting this protein had any effect on tumor growth and the metastasis”, explains to DiCYT Xosé Bustelo, CSIC research professor, who works at CIC. Besides, the scientists have a no less important second objective: check if inhibiting TC21 had any negative side effect which could dismiss treatments that attack this molecule.
The answers of these two questions mean a potential advance against breast cancer. On one hand, “if we get rid of the protein, the animals are healthy, they do not have such serious alterations that make us dismiss therapies”, comments the scientist. On the other hand, the role of TC21 is extremely relevant for the development of the illness. Suppressing this molecule avoids the growth of two most frequent breast cancer subtypes, the ones called Her2 positive (because they have a high expression of biomarker Her2) and the triple negative (which express neither Her2 nor the estrogen and progesterone receptors). In addition, “curiously, the elimination of this protein does not prevent the cells from leaving the tumor and going to peripheral tissues; however, once they reach them, they cannot survive”, comments Bustelo, which explains why there is not any register of lung metastasis.
Avoiding compensatory mechanisms
The study has also allowed the overcoming of an important setback which frequently happens in these kinds of researches. “When you make use of therapies, you play against the evolutionary process, because tumors have multiple mutations and, if you kill cells which have a specific target cell, you can favor the growth of others that have other alterations to compensate it”, adverts the expert. In this case, in spite of the fact that in the animal models which did not have the protein the tumor had not developed at the first moment, it would develop after a while due to the existence of compensatory mechanisms, which supplied the function of the missing protein. “We could characterize these mechanisms and we can prevent them”, points out Bustelo.
The research work, of which Mercedes Dosil’s lab, of CIC, also participates, has been financed by the Spanish Association against Breast Cancer Scientific Foundation since 2009 and is expected to end in September, 2014. The idea was to study the role of this protein in a physiological level and strength as therapeutic target cell in distinct kinds of cancer. The article which appears today in Nature Communications is centered in breast cancer; however, the scientists also have positive data in lymphoid and hematopoietic tumors which have not been published yet.
The next phase of the research is the development of drugs which can inhibitTC21and the group of Balbino Alarcón, a scientist of Molecular Biology Center ‘Severo Ochoa’ of Madrid has a special role in this part of the research. The scientists have already identified a series of active molecules; however, their effects have to be checked in cells, animals and patients; and, nowadays, their development is in a Spanish enterprise’s hands. “The development of inhibitors takes time and it may not succeed if one does not have the desired effects but unfavorable ones”, says Bustelo.
The protein in other tumors
On the other hand, the scientists have been analyzing the role of the protein in other tumors. The most advanced case is the lymphoid and hematopoietic tumors, but they have also been working on ovary cancer. Nevertheless, every kind of tumor has different biological signals and answers. “We suppose that part of the problem will be common compared to what we have seen in breast cancer, but we cannot exclude different processes”.
Nowadays, 85% of women who have been diagnosed with breast cancer are cured, but “we still have the problem of some tumors which are resistant to most of therapies”, comments the CIC researcher. Metastases are also difficult to treat, so the objective of this advance is to obtain complementary treatments combined with current therapies, which may help fight breast cancer that still causes many deaths.