A new research paper published in Oncotarget has highlighted how p53 affects cancer cell growth, treatment resistance, and potential drug targets, providing new insights that could improve future cancer therapies.

Researchers Jessica J. Miciak, Lucy Petrova, Rhythm Sajwan, Aditya Pandya, Mikayla Deckard, Andrew J. Munoz, and Fred Bunz from the Sidney Kimmel Comprehensive Cancer Centre and Johns Hopkins University School of Medicine studied the tumour-suppressing protein p53, which plays a key role in preventing cancer.

The p53 protein plays a crucial role in preventing cancer by stopping uncontrolled cell growth.

However, many cancers mutate or suppress p53, allowing tumours to develop and resist treatment.

In this study, researchers restored p53 function in colorectal cancer cells, which led to slower cellular growth, increased cellular ageing (senescence), and greater sensitivity to radiation therapy.

These findings suggest that p53 status influences cancer progression and response to treatment, making it a promising target for new therapies.

The study also examined hTERT-RPE1 cells; a type of non-cancerous human cell used in research.

When the TP53 gene was disrupted in these cells, they grew faster and became more resistant to radiation, reinforcing the idea that p53 helps prevent cancerous growth.

Another key discovery was a previously unnoticed p53 mutation (A276P) found in a subset of hTERT-RPE1 cells.

This mutation weakened p53’s ability to regulate certain genes but did not affect its ability to control calcium signalling, a process important for cell survival.

The unexpected appearance of this mutation suggests that even non-cancerous cells can acquire genetic changes that mimic early cancer development.

This insight could help scientists better understand how cancers evolve and become resistant to treatment.

“Cancers that retain wild type TP53 presumably harbour other clonal alterations that permitted their precursors to bypass p53-mediated growth suppression.”

A breakthrough in the study was the identification of two new p53-regulated genes that could be important for cancer treatment.

The first, ALDH3A1, helps detoxify harmful substances and may impact cancer cell resistance to oxidative stress.

The second, NECTIN4, is a protein found in many aggressive cancers, including bladder and breast cancer.

Notably, NECTIN4 is the target of enfortumab vedotin, an FDA-approved drug for bladder cancer.

These discoveries provide new potential drug targets and could lead to improved therapies for cancers that still retain some p53 function.

In conclusion, this research highlights the critical role of p53 in cancer biology and suggests that restoring p53 function could make tumours more vulnerable to radiation and chemotherapy.

The discovery of new p53-controlled genes provides new opportunities for targeted cancer therapies.

With further research, these findings could lead to new precision medicine strategies that leverage p53’s natural tumour-suppressing abilities.

Source: Impact Journals LLC