Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. (https://pubmed.ncbi.nlm.nih.gov/38181741/)
These scientists wanted to learn more about a type of lung cancer called small cell lung cancer (SCLC). They studied samples of tumors and nearby lung tissues from 112 patients who had not yet received any treatment for their cancer.
The scientists used a special technique called proteogenomic characterization, which means they looked at both the genes and the proteins in the samples. They wanted to understand how the genetic changes in the cancer cells affected the proteins and how this influenced the behavior of the cancer.
By analyzing the genes and proteins together, the scientists discovered that certain genetic changes, like mutations in a gene called FAT1, deletion of a gene called RB1, and loss of a part of chromosome 5, were important for the development of SCLC. They also found two biomarkers, which are like signs that can help doctors predict how the cancer might behave. These biomarkers were called HMGB3 and CASP10.
The scientists then wanted to understand how HMGB3 affected the cancer cells. They found that when HMGB3 was overexpressed, which means there was too much of it, it made the cancer cells more likely to move around the body. They also discovered that HMGB3 controlled the activity of certain genes that are important for cells to stick together.
Next, the scientists studied how the immune system was involved in SCLC. They found that a mutation in a gene called ZFHX3 was linked to a strong immune response in the cancer. They also noticed that when the cancer cells had high levels of DNA damage, which is like a problem with their genetic material, it could actually suppress the immune system and make it harder for the body to fight the cancer.
The scientists then grouped the SCLC samples into four different subtypes based on their genes and proteins. Each subtype had its own weaknesses that could be targeted with specific treatments. To make sure their findings were correct, the scientists tested these treatments on cancer cells grown in the lab and also on mice that had been given SCLC from patients.
Overall, this study helped the scientists understand more about SCLC and how it behaves. It also gave doctors and researchers valuable information that can be used to develop better treatments for patients with this type of lung cancer.
Liu Q., Zhang J., Guo C., Wang M., Wang C., Yan Y., Sun L., Wang D., Zhang L., Yu H., Hou L., Wu C., Zhu Y., Jiang G., Zhu H., Zhou Y., Fang S., Zhang T., Hu L., Li J., Liu Y., Zhang H., Zhang B., Ding L., Robles AI., Rodriguez H., Gao D., Ji H., Zhou H., Zhang P. Proteogenomic characterization of small cell lung cancer identifies biological insights and subtype-specific therapeutic strategies. Cell. 2024 Jan 4;187(1):184-203.e28. doi: 10.1016/j.cell.2023.12.004.