Genesde proliferacioń y apoptosis como factores predictivos y pronósticos en el ćancer de mama: Hacia una medicina personalizada

Multiple immortal cell lines are characterized by genetic alterations such as mutations of key genes in apoptosis induced by chemotherapy. This explains why some tumors without prior treatment are chemically resistant (innate tumor resistance). The coamplification of HER-2/neu and topoisomerase II plays a role in chemo-sensitivity. Apoptosis is an important regulatory mechanism in cell growth and development that leads to carcinogenesis. By losing the balance between cell proliferation and cell death or apoptosis, increases the rate of tumor growth or remission.Because many antineoplastic drugs require apoptotic pathway to induce cell death, the parameters of cellular proliferation and apoptosis are targets of study as predictors of response to chemotherapy. It has been shown that tumor cell proliferation is a factor in locally advanced breast cancer (LABC) using doxorubicin as neoadjuvant therapy, and assessing the mitotic rate and the levels of Ki-67 protein. We have also shown a significant association between the rate of cell proliferation (high mitotic frequency) and resistance to doxorubicin in a subset of tumors expressing wild p53 protein and wherein the mutated p53 gene status was the only predictive factor of chemo-resistance. So far, there is no clinic in the molecular factors predictive of response or resistance to chemotherapy. Some markers have been analyzed in several studies of patients with breast cancer in recent years. Among these are the HER-2/neu and p53 genes, which appear to be the most important. There is a relationship between TP53 mutations that affect the response to anthracyclines in patients with locoregional advanced breast cancer. Some studies suggest that specific TP53 mutation can confer resistance to anthracyclines. DNA microarrays represent a new tool for studying gene expression profiles in human tumors. Other genomic studies will be useful for studying protein expression profiles (proteomics) in cancer.