2023 World Conference on Lung Cancer (Posters)-EP03.06. Synthetic Lethality Targeting Programmed Cell Death Reverses the Osimertinib Resistance Induced by ARID1A Deficiency in LUAD

EP03.06. Synthetic Lethality Targeting Programmed Cell Death Reverses the Osimertinib Resistance Induced by ARID1A Deficiency in LUAD - PDF(Slides)

Back to course

Pdf Summary

The study conducted by Dantong Sun and colleagues from the Cancer Hospital Chinese Academy of Medical Sciences in China investigates the role of ARID1A in lung adenocarcinoma (LUAD) and the potential treatment approaches for ARID1A deficient LUAD. ARID1A deficiency has been found to promote cell growth and metastasis while rendering targeted therapy ineffective in LUAD. The researchers employed multi-omics methods to identify potential pathways and validated their findings through western blotting. They assessed the proliferative ability of ARID1A deficient LUAD cells through colony formation and 3D culturing, and evaluated their sensitivity to inhibitors using MTS assays. They also analyzed patients' sections through IHC.<br /><br />The results of the study showed that ARID1A deficient LUAD cells exhibit increased tumorigenic and proliferative ability, as well as resistance to the targeted therapy drug osimertinib. The researchers identified a novel EZH2/E2F1/PTEN axis impacted by ARID1A, which potentially regulates programmed cell death (apoptosis and autophagy) and P53 degradation. This axis ultimately affects disease progression and osimertinib sensitivity. The study suggests that EZH2 inhibitors can induce synthetic lethality in cells lacking ARID1A by targeting the EZH2/E2F1/PTEN axis and influencing MDM2 and proteasomal function. Therefore, the researchers propose therapeutic strategies for ARID1A deficient LUAD using EZH2, MDM2, and proteasomal inhibitors.<br /><br />In conclusion, ARID1A deficiency leads to cancer progression and osimertinib resistance in LUAD through the EZH2/E2F1/PTEN axis. The study highlights the potential of therapeutic strategies targeting this axis for the treatment of ARID1A deficient LUAD.

Asset Subtitle

Dantong Sun

Meta Tag

Speaker Dantong Sun

Topic Tumor Biology: Translational Biology - Translational Therapeutics

Keywords

ARID1A

lung adenocarcinoma

LUAD

ARID1A deficiency

targeted therapy

tumorigenic ability

osimertinib resistance

EZH2/E2F1/PTEN axis

programmed cell death

therapeutic strategies