2024-01-10 06:15:52
Breast cancer is the most common cancer among women; one in eight suffers from it. Receiving this diagnosis is an event that changes the life of any woman, due to the feelings that emerge and the uncertainty about what is to come. The earlier it is detected, the better the cure options, which is why breast self-knowledge, mammography and periodic consultation with a specialist are so important.
This disease consists of the abnormal multiplication of breast cells. There is no single cause that causes it but it is the product of different risk factors and lifestyles, with both non-genetic and genetic components. Of the latter, only between 5 and 10% are hereditary and can predispose to contracting the disease.
The main factors that increase the risk of developing breast cancer are age, especially after age 50, personal or family history of breast or ovarian cancer, treatment with radiation therapy to the breast, treatment with hormones, such as estrogen and progesterone after menopause, onset of menstruation at an early age or menopause at a later age, advanced age at the time of first birth or never having had children, obesity, sedentary lifestyle, drinking alcohol.
Women with breast cancer have various options to treat the disease that will depend on each individual, their health status, the type of tumor and other issues that the doctor evaluates. Some are surgery, radiotherapy, hormone therapy, chemotherapy and molecular therapy. Most require several of these strategies to combat it.
Surgery and radiotherapy are types of local treatment, that is, the tumor in the breast and/or lymph nodes is removed or destroyed. On the other hand, hormone therapy, chemotherapy and molecular therapy are systemic treatments, which means that the disease is fought throughout the body, through the blood.
A team from the Institute of Experimental Genetics of the Faculty of Medical Sciences of the National University of Rosario (UNR) in Argentina studies new therapeutic strategies to attack breast cancer, specifically the triple negative subtype, one of the most aggressive and difficult to treat. .
These strategies consist of metronomic chemotherapy and drug repositioning.
As Dr. Graciela Scharovsky explains to Argentina Investiga, the first consists of administering drugs in doses lower than the maximum tolerated doses that are routinely used to treat patients but chronically, at regular intervals, without long periods of rest.
As in the usual treatment the maximum tolerated doses are given, and these are toxic, the patient must then have periods of rest to recover; perhaps be hospitalized and receive other drugs to counteract these toxicities. “The problem is that, in these rest periods, the cells that did not die and are more resistant to the therapy begin to proliferate,” highlights the researcher.
From there arises the proposal of metronomic chemotherapy, in terms of giving low doses but without that rest. These doses do not act so much on the tumor cell but on its environment, such as the blood vessels that the tumor needs for nutrition and oxygen. Administering them chronically prevents the tumor from continuing to nourish itself and stops its growth. Another difference is that chemotherapeutic drugs not only kill tumor cells, but also other proliferating cells such as those of the immune system. In contrast, the use of low doses of certain chemotherapy drugs stimulates the response rather than inhibiting it.
Regarding drug repositioning, it consists of assigning new therapeutic objectives to medications designed for other pathologies and administering them in combination with other treatments. For example, “a chemotherapeutic such as cyclophosphamide and together with losartan, known to treat hypertension, have an important joint antitumor effect.” It should be noted that they are used in doses that generally do not cause toxicity and can be administered orally. Likewise, since these drugs are off-patent, they are available as generics and are cheaper.
Two researchers on the team. (Photo: National University of Rosario / Argentina Investiga)
Better life quality
The UNR team has been working on these lines of research for more than 25 years. Dr. María José Rico says that the studies begin with preclinical experimentation, in vitro tests, then with animals and subsequently there are several stages that must be completed to reach the clinical trial. For example, the combination of cyclophosphamide plus celecoxib – an anti-inflammatory – could be brought to the clinic in a phase I/II trial with patients with advanced breast cancer, “with very good results.”
Professionals analyze the effect of these combinations and study the cellular and molecular mechanisms by which this effect is produced, which allows us to know what is being attacked and what could be added to the therapy. And, on the other hand, they maintain permanent interaction with clinical oncologists, who are the ones who care for patients.
The truth is that these new combined therapies reduce the growth of tumors, inducing, in some cases, total regressions. Antimetastatic effects were also detected. “What is achieved is to prolong the time of life while maintaining good quality, due to the low toxicity of the treatment,” they state and highlight that in half of the patients studied a prolonged progression-free survival was obtained.
Because of this, researchers are working to make these therapies part of the official treatment battery, perhaps in advanced stages of the disease or combined with others. “Probably, the first stage requires a strong shock with the maximum tolerated dose and then, to prevent resistant cells from growing and forming metastases, including these new therapies,” says Scharovsky, who explains that they are not yet official because they need to add a greater clinical evidence.
It should be noted that, although these therapies are being investigated in several countries, the UNR team was a pioneer in establishing the combination of the drugs cyclophosphamide with celecoxib and losartan for breast cancer, whose encouraging results were published in different academic journals. The latest results obtained, using cyclophosphamide and losartan, were published in the academic journal Oncotarget.
Currently, they are also developing another line of research on breast cancer in animals that have this disease and metabolic syndrome with good preclinical results. “The combination of obese patients with metabolic syndrome and the development of breast cancer is very common, which makes therapy difficult,” they explain.
Doctors Graciela Scharovsky, María José Rico, Viviana Rozados and Leandro Mainetti are part of the team at the Institute of Experimental Genetics of the UNR Faculty of Medical Sciences. (Source: National University of Rosario / Argentina Investiga)
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