Cell Rep: Study reveals therapeutic targets for malignant lung cancer

December 4, 2020 //--- Currently, about one-third of lung adenocarcinoma patients can be effectively treated with targeted therapies, but for the other two-thirds of these cancer patients, treatment options are fewer.
in a recent study, Scientists at Memorial Sloan Kettering reported new findings about a particularly aggressive substum of lung adenocarcinoma, driven by two mutations that often occur simultaneously, called KEAP1 and STK11.
changes in the characteristic molecules of these tumors prevent a cell death process called Ferroptosis.
the study was published in the journal Cell Reports on December 1, 2020.
(Photo Source: www.pixabay.com) Ferroptosis is a type of programmed cell death that relies on iron.
was discovered less than a decade ago, but it has become an important target for cancer treatment and drug treatment for other diseases.
when ferroptosis does not work properly, cells may grow uncontrolled.
two genes, STK11 and KEAP1, work together to create a special micro-environment.
combination of these two gene mutations has been found in more than 10 percent of lung adenocarcinomas, so drugs that can successfully target this change will have a meaningful impact.
In this study, lead author Corrin Wohlhieter used the gene editing tool CRISPR to create three types of cells: some with STK11 genes being knocked out, some with KEAP1 genes being knocked out, and some with two genes being removed.
, she isolated each of the three cell types and studied them separately in the lab.
by analyzing the behavior of the cells, she was able to identify which other genes were activated when STK11 and KEAP1 were lost.
" lung cancer is often very heterogeneic, so without such controlled trials, it is difficult to isolate changes attributed to a particular gene or group of genes.
by creating these genes to knock out cell lineages, we can really focus on the cells that have these mutations and link any behavior we observe to the presence or failure of these factors.
researchers found that cells with both STK11 and KEAP1 mutations also had high levels of expression of other proteins that made them resistant to Ferroptosis.
one of the proteins, called SCD1, is a particularly good target for these tumors, the authors note.
our existing SCD1 inhibitors are not working very well, many MSK laboratories are actively working on strategies for Ferroptosis abnormalities in targeted cancer cells," he said.
" (Bioon.com) Source: Unexpected find reveals new target for aggressive form of lung cancer Original source: Corrin A. Wohlhieter et al, Concurrent Mutations in STK11 and KEAP1 Promote Ferroptosis Protection and SCD1 Dependence in Lung Cancer, Cell Reports (2020). DOI: 10.1016/j.celrep.2020.108444。