Release date: 2018-05-29
The more you know about the mechanisms that contribute to tumor cell survival, the more likely it is to destroy the tumor. An article published online by Cancer Cell on May 24th shows that the research team led by ICREA researcher Angel R. Nebreda revealed a new protective mechanism for breast cancer cells and identified new therapeutic targets. Funded by the European Research Council (ERC).
Breast cancer is one of the most lethal tumors in women, causing 521,000 deaths worldwide each year. It can be divided into three types: estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) positive or Three negative. Among them, three negative breast tumors accounted for 15% of breast tumor cases. The only effective treatment method is chemotherapy. The other two breast tumors can also use targeted therapy. Therefore, this study may be used to improve the treatment of triple negative breast cancer. Flat road.
The experiment was carried out in a mouse model of triple-negative breast tumors. The researchers found that p38α protein (hereinafter referred to as p38) protects tumor cells by opening a DNA repair mechanism, and p38 protects tumor cells from DNA errors or excessive accumulation of mutations. "Tumor cells tend to accumulate DNA damage, but in some tumors this accumulation is more, and we have observed that these cells are more dependent on the activity of p38," Nebreda explained.
Block p38 to optimize chemotherapy
The researchers used p38 inhibitors to block the role of this protein in tumor cells, and these inhibitors have been used in patient-related clinical assays in other diseases. In this study, p38 inhibitors were used in combination with traditional chemotherapy drugs, taxanes such as paclitaxel and docetaxel. As expected, tumor cells treated with combination therapy showed greater genomic instability, meaning that they carried more DNA damage and more chromosomal variation. Therefore, these tumor cells are largely killed, and the tumor mass is largely atrophied.
Subsequently, the researchers used nine tumor cells from patients to establish a mouse model, and found that in seven of them (including ER and triple negative), the anti-tumor effect of taxanes when enhancing the use of p38 inhibitors Increased or prolonged anti-tumor time.
"The taxane prevents cell division by destroying the chromosome and causing chromosomal instability. As speculated, p38 blocks this effect, and if the function of this protein is turned off in cells, the anticancer effect of taxanes It will become more effective," said the first author of the article, Begoa Cánovas.
Differentiate between different types of patients
There are two types of tumor cells left untreated for treatment, and the researchers believe they have found a possible explanation and can therefore distinguish between different patients, who have observed that the effectiveness of treatment depends on the chromosomal instability of tumor cells. The degree of instability, the more effective the treatment.
"From an application point of view, this is one of the most interesting findings of this study, because the method for determining tumor chromosomal instability is simple, but our findings require more experimental confirmation," Nebreda said. He expressed the hope that more laboratories would participate in the study, and if the results were confirmed, later pharmaceutical companies could begin to test the effectiveness of this combination therapy in clinical trials.
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"Tumor cells evade death through in extremis DNA repair"
Source: Medical Valley
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