A new study from the University of Oklahoma has provided a new understanding of large cell neuroendocrine carcinoma (LCNEC), a rare and aggressive type of lung cancer.
Currently, LCNEC has a high chance of metastasis, no standard treatment and a poor survival rate.
“Given the rarity of this cancer, we have not understood a lot about it,” stated Abdul Rafeh Naqash, a medical oncologist and associate professor of medicine at the University of Oklahoma College of Medicine and co-senior author of the study.
“In this study, we have examined two types of information: molecular data, which helps us understand this tumour and its subtyping, and clinical outcomes.”
The world’s most detailed study of a rare lung cancer
The new study is considered to be the most comprehensive characterisation of LCNEC to date.
To better understand the workings of this rare lung cancer, the research team analysed data from 590 patients across numerous health systems in the United States and Europe.
To better understand the molecular makeup of LCNEC, the research team partnered with Caris Life Sciences, which provided comprehensive molecular profiling datasets.
They found that LCNEC shares features with the better-known small cell lung cancer and non-small cell lung cancer, yet there were aspects of LCNEC that didn’t resemble either. Machine learning helped to differentiate those unclassified tumours.
Protein’s role in evading the immune system
Researchers also found promising news regarding a protein involved in LCNEC. The protein, called FGL1, plays a role in helping cancer evade the body’s immune system by deactivating immune cells.
However, current drugs are available to inhibit FGL1, potentially resulting in the reactivation of immune cells and killing the tumour.
James Hamrick, chairman of the Caris Precision Oncology Alliance at Caris Life Sciences, explained: “This highly collaborative study provides insights into the biology of LCNEC and suggests new avenues for treatments.
“We look forward to improvements in patient outcomes in LCNEC as this line of scientific inquiry continues.”
LCNEC doesn’t respond well to immunotherapy
In addition, researchers found that LCNEC tends to have less infiltration of a type of immune cell called T cells, which means the T cells are not as likely to recognise and attack tumour cells.
The T cell finding also indicates that LCNEC will not respond as well to immunotherapy, as the researchers found in their examination of clinical data. Patients with LCNEC did not fare better when receiving immunotherapy, either alone or in addition to chemotherapy.
Looking to the future: Clinical trials for more precise treatments
As there is no Food and Drug Administration-approved treatment for LCNEC, clinicians are often of two schools of thought regarding how to treat the cancer – either as small cell lung cancer or non-small cell lung cancer.
Naqash said he hopes the study sets the stage for clinical trials so that a more precise treatment for this rare lung cancer can ultimately be found.
“This is one of the first attempts at unravelling the molecular heterogeneity within large cell neuroendocrine carcinoma, as well as understanding clinical outcomes to the current treatment approaches,” he said.
“What we are trying to show in this paper is that one size does not fit all. There is a lot of complexity in LCNEC.”