Susanna Greer: Lung Cancer Knocked on the Wrong Door
Susanna Greer, Chief Scientific Officer at the V Foundation for Cancer Research, published the following newsletter on LinkedIn:
“This week’s Cool Cancer Find has significant implications for cancer research and the potential for impact on lung cancer patients, particularly those with lung adenocarcinoma, which is the leading cause of cancer-related deaths worldwide.
The V Foundation grantee Dr. Carla Kim and her team of researchers at Boston Children’s Hospital published an impactful study highlighting the role of surfactant-producing alveolar type 2 cells, which normally help repair lung tissue by developing into alveolar type 1 cells.
Dr. Kim and her colleagues show how these cells are involved in the early stages of lung adenocarcinoma development when they carry mutation in the gene KRAS.
To understand how this works, imagine a neighborhood where houses (lung cells) can change and repair themselves after a bad storm (an injury). Normally, one type of house, let’s call them Type A houses, can transform into another type, Type B houses, to help with the repairs.
Before these houses start repairing themselves, they enter a phase where they temporarily stop doing normal things. However, if a criminal (the KRAS mutation) moves into the neighborhood during this phase, it hijacks this phase to build secret hideouts, leading to more crime (in this case cancer) in the neighborhood.
By studying this phase, Dr. Kim and her team discovered that these hideouts have weaknesses we can exploit —like faulty doors (called integrin and SRC signaling pathways)—that can be targeted to stop the criminal activity.
Although previous attempts to fix these doors didn’t work well in well-established crime areas, the new findings from Dr. Kim’s lab suggest that targeting these weak points early, along with other strategies (like combining SRC and KRAS inhibitors), could be much more effective.
This could lead to new ways to prevent the crime wave in the first place (lung cancer!) from taking over, keeping the neighborhood safe and healthy.
Moreover, Dr. Kim and her team found that targeting these faulty doors with specific small molecules (like integrin and SRC inhibitors) could prevent the criminals from establishing their hideouts in the first place.
Although previous attempts to use SRC inhibitors like Dasatinib failed in treating advanced lung cancer, this study suggests that using them in combination with KRAS inhibitors (like MRTX1133) at early stages could be more effective. Additionally, they discovered that inhibiting KRAS induces a Type B-like state in normal Type A cells. Incredible, right?!
Overall, these findings highlight the potential for new therapeutic strategies that target the unique injury-associated transitional cell states driven by mutations, offering a promising approach to intervene in early-stage lung cancer and prevent its progression.
Follow Dr. Kim and her lab here and and read her paper at Early-stage lung cancer is driven by a transitional cell state dependent on a KRAS-ITGA3-SRC axis.”
Source: Susanna Greer/LinkedIn