A new study from the University of Oklahoma offers a new understanding of large cellular neuroendocrine cancer (LCNEC), a rare and aggressive type of lung cancer.
Currently, LCNEC has a high chance of metastasis, lacking standard treatment, and survival rates are low.
“We don’t understand much about it given the rarity of this cancer,” said Abdul Rafeh Naqash, a medical oncologist and associate professor at the University of Oklahoma School of Medicine and a co-author of the study.
“This study looked at two types of information: the tumor and its subtyping, as well as molecular data that will help us understand the clinical outcome.”
The most detailed study of rare lung cancer in the world
This new study is considered to be the most comprehensive characterization of LCNEC to date.
To better understand how this rare lung cancer works, the researchers analyzed data from 590 patients from numerous healthcare systems in the US and Europe.
To better understand the molecular composition of LCNEC, the research team partnered with Caris Life Sciences to provide a comprehensive molecular profiling data set.
They found that LCNEC shares characteristics with the better known small cell and non-small cell lung cancers, but also did not resemble aspects of LCNEC. Machine learning helped to distinguish between those unclassified tumors.
The role of proteins in avoiding the immune system
The researchers also discovered promising news about proteins involved in LCNEC. A protein called FGL1 plays a role in helping cancer avoid the body’s immune system by abolishing immune cells.
However, current drugs are available to inhibit FGL1, potentially leading to immune cells reactivation and killing tumors.
James Hamrick, chairman of the Charis Precision Tumor Alliance for Charis Life Sciences, explained:
“As this series of scientific research continues, we look forward to improving outcomes for patients with LCNEC.”
LCNEC does not respond well to immunotherapy
Furthermore, the researchers found that LCNECs tend to have less invasion into immune cells, a type of T-cells. This means that T cells cannot recognize and attack tumor cells.
The T-cell discovery indicates that LCNECs do not respond to immunotherapy in a similar way, as researchers found in testing clinical data. Patients with LCNEC were not better when receiving immunotherapy alone or in addition to chemotherapy.
Looking to the future: clinical trials for more accurate treatment
Because there are no LCNEC Food and Drug Administration-approved treatments, clinicians often have two schools of ideas about how to treat cancer as small cell lung cancer or non-small cell lung cancer.
Naqash said he hopes the study will set a stage for clinical trials so that it will eventually be found.
“This is one of the first attempts to unravel molecular heterogeneity within large cellular neuroendocrine carcinomas and to understand the clinical outcomes for current therapeutic approaches,” he said.
“What we’re trying to show in this paper is that one size doesn’t fit all. There’s a lot of complexity in LCNEC.”
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