Small-cell lung cancer (SCLC) accounts for around 15% of all lung cancer cases. Despite recent advances, researchers have few tools to help determine those patients who are likely to have them. According to a study published in Cell Reports Medicine, scientists have identified a stem-like state in small-cell lung cancer that identifies patients with exceptionally poor outcomes following chemotherapy.
SCLC-SL Subtype Linked to Poor Survival Outcomes
This newly identified state is called SCLC-SL and was associated with shorter survival among patients with extensive-stage small lung cancer. This implies that the disease has spread beyond one side of chest. “We identified a previously unrecognized stem-like regulatory state of small-cell lung cancer by examining how DNA is packaged and which regions of the genome are accessible to the tumor cell,” said Anish Thomas, MD, the Roswell Park Professor of Hematology and Oncology and senior author of the study.
Researchers Use Chromatin Analysis to Classify SCLC
In this study, the team has analyzed the chromatin landscape of SCLC and examined the regions of genome which are accessible to the tumor cells. Most previously SCLC classification systems have relied on bulk gene-expression profiles and the limitation of this approach is that RNA measured from a tumor reflects a mix of cancer cells and surrounding immune and stromal cells. With the purpose of overcoming this, the researchers analyzed patient-derived xenograft tumors. They used a technology called ATAC-seq to map chromatin accessibility. The team then integrated data with gene-expression profiles from over 800 tumors across multiple patient cohorts.
SCLC-SL Patients Show Shorter Median Overall Survival
In the clinical trial, patients with SCLC-SL tumors had median overall survival of 7.41 months in comparison to 15.9 months for the immune-active subtype and 12.6 months for neuroendocrine subtype. According to the study, the association remained significant even after accounting for liver metastases, brain metastases and elevated lactate dehydrogenase levels.
Stem-Like Tumor State May Offer New Research Directions
“To our knowledge, this is one of the first studies to show that a SCLC molecular feature has independent prognostic significance after accounting for established clinical risk factors, including liver and brain metastases and serum levels of LDH,” Thomas said.
Their findings also suggest that SCLC tumors are more dynamic. The team now plans to determine what drives tumors into the stem-like state and whether this process can be reversed or prevented.
The information shared in this blog is for educational purposes only.
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