Could Targeting Supra-Carcinoids be the Future of Lung NET Research?

Lynnette Fernandez-Cuesta, PhD, team leader at the International Agency for Research on Cancer (IARC-WHO), is spearheading a transformative shift in the understanding of lung neuroendocrine neoplasms. Backed by the Petersen Accelerator Grant from the Neuroendocrine Tumor Research Foundation (NETRF), her work addressed the complex biological spectrum of lung tumors, including small cell lung cancer (SCLC), large cell neuroendocrine carcinomas (LCNEC), and carcinoids.

A decade of research led by Fernandez-Cuesta has unveiled supra-carcinoids, a newly identified biological entity. While these tumors mimic the morphology of standard carcinoids, they exhibit the aggressive molecular and clinical behavior typically seen in SCLC. Her team has also identified specific evolutionary trajectories and sub-groups, such as early-onset tumors that preferentially affect women.

With the support of the Accelerator Grant, Fernandez-Cuesta aims to utilize single-cell RNA sequencing and proteomics to characterize the heterogeneity of these aggressive cell pockets. By identifying the "key players" in tumor progression, her team seeks to translate high-resolution biological data into clinically accessible biomarkers. This research moves the field closer to real-time interception strategies, offering hope for earlier detection and targeted intervention for patients who are high-risk.

CancerNetwork: Are you able outline the research you conducted that resulted in your receipt of the Petersen Accelerator Grant?

Fernandez-Cuesta: Over the past 10 years, I have worked in the field of lung neuroendocrine neoplasms, including SCLC, LCNEC, and lung NETs, also known as carcinoids. This research has led to findings that have defined the current knowledge in the field. Investigating these diseases led to the discovery of supra‑carcinoids, a new biological entity with the morphology of carcinoids but the molecular and clinical behavior of the more aggressive SCLC and LCNEC. We have also uncovered other groups of lung neuroendocrine tumors, including a group of early onset tumors that occur preferentially in women, and we have discovered evolutionary trajectories that lead to each of these groups. These breakthroughs have opened new avenues for understanding who develops lung neuroendocrine tumors, as well as how and why for tumors with aggressive behavior.

How do you plan to apply the grant to the next steps of your research?

The obtained funding is aimed at depicting all the key players in the development of these aggressive supra‑carcinoids and subsequently identifying potential strategies to intercept their progression. Many tumors seem to be heterogeneous, with small pockets of aggressive supra-carcinoid cells among many less aggressive tumor regions. With the grant, we will have the means to characterize these aggressive cells to understand what makes them unique and thus find ways to detect them earlier and target them.

How do you envision the integration of single-cell RNA-sequencing and proteomic data into routine clinical workflows to guide real-time interception decisions for high-risk patients?

The new technologies are not specifically designed for the clinic but rather to provide the depth needed to depict the biological processes. Once our understanding is sufficiently deep and we have high-resolution information, the goal is to identify key biomarkers of a given process that can be used as surrogates of the biological process and can be assessed using more clinically friendly technologies, such as targeted sequencing, targeted transcriptome, immunohistochemistry or fluorescence in situ hybridization.

Is there anything else that you would like to highlight?

I would like to thank NETRF for their continuous support. This is the fourth time they have funded the research undertaken by our team, and without them, we would not have been able to make such progress in the field of rare lung neuroendocrine tumors.

Reference

Characterization of supra-carcinoids cell states to inform interception strategies. Neuroendocrine Tumor Research Foundation. Accessed March 12, 2026. https://tinyurl.com/mrehxemy