Listen to a blog summary of a research paper selected as the cover for Volume 14, Issue 8, entitled, "Wild type and gain of function mutant TP53 can regulate the sensitivity of pancreatic cancer cells to chemotherapeutic drugs, EGFR/Ras/Raf/MEK, and PI3K/mTORC1/GSK-3 pathway inhibitors, nutraceuticals and alter metabolic properties."

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Patients over the age of 50 years old who have been diagnosed with pancreatic cancer have a poorer rate of survival compared to younger patients. This means that pancreatic cancer is a disease associated with aging. The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC) and it is frequently diagnosed in its later stages. PDAC is often refractive to chemotherapies and develops resistance to inhibitors and other drugs. Therefore, there is a critical need for researchers to discover novel strategies to overcome drug resistance in PDAC cells.

One potential strategy is to focus on a key gene known for its involvement in many cell processes, including drug resistance and metabolism: TP53. The TP53 gene is often mutated or deleted in cancer cells, which can lead to drug resistance and cancer metastasis. In PDACS, this tumor suppressor gene has been shown to be mutated in 50–75% of patients.

“Many genes have been implicated in PDAC including KRAS, TP53, CDKN2A, SMAD4 and PDGFβR [3, 8, 9, 18–22].”

In a new study, researchers—from Brody School of Medicine at East Carolina University, Università di Bologna, University of Parma, and University of Wroclaw—further elucidated TP53’s role in drug resistance in PDAC cells. On April 27, 2022, their research paper was published in Aging (Aging-US) on the cover of Volume 14, Issue 8, and entitled, “Wild type and gain of function mutant TP53 can regulate the sensitivity of pancreatic cancer cells to chemotherapeutic drugs, EGFR/Ras/Raf/MEK, and PI3K/mTORC1/GSK-3 pathway inhibitors, nutraceuticals and alter metabolic properties.”

Full blog - https://aging-us.org/2022/05/tp53-restoration-sensitizes-pancreatic-cancer-to-multiple-drugs/

DOI - https://doi.org/10.18632/aging.204038

Corresponding author - James A. McCubrey - [email protected]

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Keywords - aging, TP53, targeted therapy, PDAC, metabolic properties, chemotherapeutic drugs

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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