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p53 is one of the most interesting targets for cancer therapy development, because more than 50% of cancer patients carry mutations in the TP53 gene encoding p53 protein
A recent study published in Cancer Discovery recently revealed the new functions of p53.
In cells, the function of p53 is inhibited by the naturally expressed MDM2 protein.
To their surprise, activation of p53 can lead to the expression of endogenous retroviral (ERV) sequences in the cell genome
Usually, an important role of p53 is to inhibit the expression of ERV sequences, but in this study, activation of p53 stimulated the expression of certain ERV sequences
Further studies have found that the expression of ERV sequence triggers the antiviral response of human cells, leading to an increase in the level of interferon with antiviral ability
▲P53 activated by drugs can stimulate antiviral interferon response, increase T cell infiltration, and promote the efficacy of immune checkpoint inhibitors (picture source: reference [2])
These results show that there is a synergistic effect between drugs that block MDM2 and cancer immunotherapy, which is worthy of further exploration
Aprea Therapeutics, a company co-founded by Professor Selivanova, is already developing a p53 activator
Note: The original text has been deleted
Reference materials:
[1] New cancer findings can give wider access to immunotherapy.