Scientists have discovered that the mechanism that causes cell aging can help people fight cancer. A new study from the University of Diderot in Paris showed that the targeted treatment of acute promyelocytic leukemia can cause a series of molecular events, make leukemia cells aging, and cure patients on this basis. Research indicates that this mode of action can also be used to treat other types of cancer. The article was published in the journal Nature Medicine under Nature.
The acute promyelocytic leukemia APL is caused by the fusion protein PML-RARA, which interferes with the signal transduction of nuclear receptors and the assembly of PML nucleosomes. At present, people usually use retinoic acid RA and arsenic for targeted treatment of this disease. Patients receiving this treatment can recover their health, but people do not yet understand the specific effects of these drugs on cancer cells. According to reports, APL is the only malignant disease that can be completely cured by targeted treatment.
Previously, Professor Hugues de Thés of Paris Diderot University found that the combination of retinoic acid and arsenic can trigger different pathways, leading to the degradation of PML-RARA, thereby clearing leukemia stem cells. But the researchers are still unclear about the relationship between these two events, so they further analyzed the cellular and molecular mechanisms of targeted therapy.
In this new study, the researchers revealed the necessary factors required to eradicate leukocytes, and showed a series of important events caused by drugs. Studies have shown that the treatment of retinoic acid RA and arsenic causes leukemia cells to enter the aging stage, thereby inhibiting their proliferation.
The researchers found that after drug treatment, p53 protein became the arbiter of cell life and death, it can trigger cell senescence through the PML nucleus. The PML nucleus is a spherical structure in normal cells, but PML / RARA in leukemia disrupts its structure. Studies have shown that the treatment of retinoic acid RA and arsenic can restore the PML nucleus, activate p53 and cause cell senescence. The loss of any link in this series of events (drug therapy, ML / RARA degradation, nucleosome reformation, p53 activation) will lead to treatment failure.
The combined treatment of retinoic acid and arsenic eliminates disease cells through the above mechanism and helps patients recover health. This treatment can save patients from receiving chemotherapy and avoid many serious side effects.
This study showed the mechanism of successful treatment of APL by retinoic acid RA and arsenic. The researchers pointed out that activating the same PML / p53 pathway in other types of cancer may also have a good therapeutic effect.
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