General
Tianwei Chen from the Walter and Eliza Hall Institute of Medical Research (Melbourne, Australia) will be visiting Amsterdam UMC on the 6th of May.
As part of her visit, Tianwei will deliver a lecture at Amsterdam UMC, location VUmc PK1Y141 on Monday 6th May at 3 pm. She will delve into the topic of the role of mutant TP53 in lung cancer, using genetically engineered mouse models.
Tianwei Chen is a PhD student at the Walter and Eliza Hall Institute of Medical Research, co-supervised by Associate Professor Gemma Kelly, Professor Kate Sutherland, and Professor Andreas Strasser.
Her research focuses on investigating the role of mutant TP53 in lung cancer using genetically engineered mouse models. TP53, a tumor suppressor gene, is mutated in approximately 50% of human cancers, leading to poor therapeutic responses. Mutant TP53 proteins have been found to promote tumor development through various mechanisms, including loss of function (LOF), dominant negative effects (DNE), and gain of function effects (GOF).
Despite extensive research efforts, the relative contributions of these effects to tumorigenesis are largely unknown. Tianwei's PhD study aims to understand the importance of these effects in the initiation and expansion of lung adenocarcinoma (LUAD). Using novel LUAD mouse models with inducible mutant Kras-G12D and switchable Trp53 status, Tianwei and her team are unraveling the immediate and long-term effects of different Trp53 states on tumor growth.
Preliminary data shows that converting mutant Trp53 back to wild-type Trp53 induces cellular senescence and cell cycle arrest in LUAD cells in vitro, significantly delaying tumor progression in vivo and improving overall survival in mice. Conversely, converting mutant Trp53 into a Trp53 knock-out state does not delay tumor growth. Additionally, restoring wild-type Trp53 enhances the effectiveness of the KRAS-G12D inhibitor MRTX1133 in killing lung cancer cells in vitro.
These findings highlight the critical role of the LOF effects of mutant TP53 in sustaining the expansion of mutant KRAS LUAD. Furthermore, the restoration of wild-type Trp53 shows synergistic therapeutic effects with MRTX1133, offering promising implications for the development of novel therapeutic approaches for lung cancers expressing mutant TP53.