﻿Hypoxia in the TME is usually related to increased resistance to apoptosis, angiogenesis, and migration [206]. of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets. strong class=”kwd-title” Keywords: Breast tumors, Purinergic receptors, Ectonucleotidases, Tumor progression, Therapeutic possibilities Introduction Considering the relevance of breast cancer (BC) in the health scenario, it becomes even more relevant to understand the pathophysiological pathways involved in its development and control. In this context, the relationship between the purinergic system and the processes of survival, proliferation, invasion, and migration of breast tumor cells emerges. This correlation opens therapeutic possibilities that until then were not used to control BC. Taking this information into consideration, we seek to build a bibliographic review using the databases Pubmed, Scielo, Lilacs, and ScienceDirect, which addressed the main aspects of BC and its correlations with the purinergic system, visualizing new therapeutic possibilities and addressing those that are under development, allowing the discussion of topics that may evolve to improve the prognosis and quality of life of thousands of people affected by this neoplasm. Epidemiology The BC is one of the three most common cancer types in the world, after lung and colon cancer [1], and is the most frequent cause of death in women [2, 3]. According to Globocan [4], around 2.09 million women worldwide were diagnosed with this neoplasm in 2018, of which 626 thousand deaths occurred as a result of the disease. Annually, 1.7 million new cases are diagnosed, which means one case every 18?s [5]. In the USA, BC represents 14% of newly diagnosed cancers [6], and the estimate for 2020, for women, is about 276 thousand new cases and 42 thousand deaths [7]. In BRD4770 view of this, it is notable that despite significant advances in the research scenario, BC is still a worldwide public health problem, and thus, it represents a priority in medical research [8]. Risk factors In women, the etiology of BC is multifactorial, involving environmental (most prevalent) and genetic factors. Among the environmental factors, the female gender stands out; advanced age; the race, that although BC in the USA is more prevalent in white women [9], black women are more likely to have human epidermal growth factor type 2 receptor (HER2) positive cancer [6, 10, 11], be more aggressive and with a worse prognosis [12, 13]; increased weight and body fat (mainly in postmenopause) [14, 15]; high levels of endogenous estrogen in the postmenopause [16, 17]; early menarche (before age 13) and late menopause [18]; nulliparous women with late first pregnancies [19, 20]; alcohol consumption [21C24]; and tobacco use (including secondhand smoke) [25C27]. In addition, protective factors are breastfeeding [28] and physical activity [29]. On the other hand, in relation to genetic factors, family history and gene mutations are involved. As for family history, studies have shown that the risk for BC increases twice as much, if the woman has an affected first-degree relative [30, 31]. Genetic mutations, in turn, happen directly in only 5% of cases, and can occur mainly in the BRCA, p53, STK11, CDH1, PALB2, and PTEN genes and in the mismatch repair genes [9]. Only within the BRCA1 gene, more than 1800 mutations have been identified, BRD4770 a fact that increases the risk of BC for men and women [3]. Pathogenesis The BC occurs when there is unregulated cell growth within any of the components of the breast (lobes, ducts, adipose tissue, and lymphatic tissue) [32]. About 80% of BC cases start in the mammary duct epithelium [33]. This unregulated growth starts with modifications in the cell cycle, due to changes in genetic information [9]. Normally, it begins with an uncontrolled proliferation, loss of normal cellular characteristics, loss of responses Rabbit Polyclonal to ARHGEF11 to growth and proliferation-inhibiting factors, and a change in metabolism that favors tumor cell populations [34]. Lastly, it results in a painless breast nodule [3]. After the formation of the breast nodule, BC can advance to other tissues. The metastatic process involves changes in cell adhesions and the extracellular BRD4770 matrix, which.