Study uncovers target to overcome resistance in ARID1A-mutant cancers
MD Anderson Research Highlight July 16, 2025
Many ovarian clear cell carcinomas (OCCCs) have mutations that inactivate the ARID1A tumor suppressor and are associated with resistance to standard treatments and poor patient prognoses. To provide insights into the underlying mechanisms, researchers led by , examined ARID1A-mutant OCCC cells. They found that ARID1A mutations create a dependence on the alanine amino acid through regulating alanine transporter proteins including SLC38A2, which acts as a gatekeeper to support rapid cancer growth. Inhibiting SLC38A2 led to reduced alanine, slowed cell growth and tumor shrinkage. Additionally, SLC38A2 inhibition enhanced the activity of immune checkpoint blockade in vivo and chimeric antigen receptor (CAR) T therapy in vitro. These results suggest that targeting alanine transport alone or in combination with immunotherapy is a promising therapeutic strategy for ARID1A-mutant cancers. Learn more in .
This study deepens our understanding of this difficult cancer type and hopefully lays the groundwork for targeting alanine transport as a therapeutic strategy.