In a new study published in Nature Cell Biology, researchers used CRISPR/Cas9 in vivo somatic engineering to make mouse models of small cell lung cancer (SCLC) that either expressed KDM6A (KDM6A-WT) or were inactivated for KDM6A (KDM6A-Mutant). KDM6A is an epigenetic modifier that is mutated in human SCLC.
KDM6A inactivation in an autochthonous SCLC mouse model promotes NEUROD1 expression leading to SCLC tumors that express both ASCL1 and NEUROD1. a, Schematic of the adenovirus used for IT injection into the lungs of LSL-Cas9 mice to generate autochthonous SCLC tumors that are Kdm6a inactivated or Kdm6a WT. RPP: sgRb1, sgTrp53, sgRbl2; sg"T": sgKdm6a or sgControl .
Mutations in epigenetic drivers like KDM6A can lead to plasticity in different subtypes of SCLC. A surprising observation is that a single mutation can have a profound impact on these subtypes. Although KDM6A is likely not a good drug target directly, as its loss promotes intra-tumoral heterogeneity, this work suggests that identifying epigenetic drivers that when inhibited promote SCLC subtype plasticity toward more homogenous molecular subtypes may be effective strategies to combine with other therapeutic approaches that selectively target a subtype vulnerability.
Future studies will focus on identifying other druggable epigenetic drivers that may oppose the function of KDM6A or when inhibited block intra-tumoral subtype heterogeneity.Leslie Duplaquet et al, KDM6A epigenetically regulates subtype plasticity in small cell lung cancer,
Danmark Seneste Nyt, Danmark Overskrifter
Similar News:Du kan også læse nyheder, der ligner denne, som vi har indsamlet fra andre nyhedskilder.
The hidden gem Glasgow park packed with nature and a wee cafe everybody lovesNewlands Park is squirrelled away in the southside and might not be known by most but it's a great place for young families and dog walkers and even offers a great wee cafe that people love to eat in.
Læs mere »
Hope Your Flowers Bloom: Nature and working class masculinity explored in new playBILLY Connolly famously called inner city schemes “deserts wi’ windaes” and for Clydebank-born Raymond Wilson the description resonates.
Læs mere »
Calls for ‘ecocide’ law to punish those who destroy nature like war criminalsScotland could become one of the first countries to establish a specific crime for mass environmental destruction as championed by late Scots barrister Polly Higgins.
Læs mere »
A KRAS solution method overcomes the undruggable obstacleResearch conducted by Revolution Medicines, California, and Memorial Sloan Kettering Cancer, New York, has developed a method to bypass the undruggable nature of a common oncogene mutation that drives cancer development and resistance to existing therapies.
Læs mere »
Small boat migrant arrivals top 25,000 since start of Sunak premiershipLabour accused the Prime Minister of failing to get a grip on the migrant crisis in the English Channel.
Læs mere »
Small boat migrant arrivals top 25,000 since start of Sunak premiershipLabour accused the Prime Minister of failing to get a grip on the migrant crisis in the English Channel.
Læs mere »