09 July 2020
Rare type of brain cancer reversed
Published online 31 December 2015
Premalignant and malignant lesions can be reversed by restoring the expression of p53 tumour suppressor gene.
Restoring p53 in premalignant hyperplastic and malignant p53-deficient pineal lesions, a rare kind of brain cancer, can reverse its malignant state, according to a new study.
Gene p53 acts as guardian against cancer through several mechanisms, including controlling the cell cycle. The loss or inactivity of this gene leads to uncontrollable cell division and eventually tumour formation, a multi-step process. At first, the tissue undergoes hyperplasia, which is increased cell division rate leading to encapsulated expansion of the tissue, that then turns malignant by invading the surrounding tissues.
But scientists from Lebanon, Qatar and the UK now show that restoring the deficient p53 in pineal gland tissues that underwent hyperplasia for short and long periods induced cellular senescence and cell cycle exit, and hence can reverse the premalignant state.
"Restoration of P53 can be effective in stopping pre-tumorigenic lesions, an approach that may be useful in patients with high-risk premalignant conditions," says co-author Raya Saab from the Children's Cancer Institute at the American University of Beirut in Lebanon.
However, the reversal needs a co-factor such as etoposide, a DNA damage inducer.
Maintaining the activation of p53 is mandatory, the researchers say, otherwise the senescent cells will re-invade the cell cycle.
“Combining the P53 restoration with therapies targeting the upstream signals responsible for inactivating the p53 gene may be most effective in malignant tumours,” says Saab.
Harajly, M. et al. P53 restoration in induction and maintenance of senescence - differential effects in premalignant and malignant tumor cells. ASM Molecular and Cellular Biology http://dx.doi.org/10.1128/MCB.00747-15 (2015)