New look at why rare cancer often evades treatments

28 Sep 2023
New look at why rare cancer often evades treatments

Researchers at Boston Medical Center and Dana-Farber Cancer Institute conducted one of the first-ever analyses of neuroendocrine tumours (NETs) at single cell resolution, unlocking new insights into this rare and often hard-to-treat cancer.

The findings, published in Science Advances, represent a tremendous leap forward in understanding why these tumours are largely resistant to immunotherapy and provide key insights that could lead to future treatments.

“This study was a tour-de-force that catalysed the efforts and innovations of researchers across Boston – including Boston Medical Center and Dana-Farber Cancer Institute - and has resulted in a better understanding of the molecular drivers of these heterogeneous, difficult-to-treat tumours,” said co-author Matthew Kulke, MD, chief of haematology/oncology at Boston Medical Center, Co-Director of the BU/BMC Cancer Center, and the Zoltan Kohn Professor at Boston University Chobanian & Avedisian School of Medicine.

“The findings represent a potential first step towards opening up new potential treatments for patients who have neuroendocrine tumours.” 

Neuroendocrine cells are found in organs throughout the human body and send messages through hormones that help the body function.

In adults, NETs often originate in the gastrointestinal tract, pancreas, and lung. Despite new forms of treatment, the tumours remain difficult to treat and are largely resistant to immunotherapy, which has revolutionised treatments for other cancers.

In part, the reason for this challenge is that the understanding of the underlying biology of NETs was incomplete.

“This study provides remarkable insights about the heterogeneity of neuroendocrine tumours and the tumour and immune microenvironment,” said Jennifer Chan, MD, MPH, Clinical Director, Gastrointestinal Cancer Center, Dana-Farber Cancer Institute.

“We are currently building on this work with the aim to discover new therapeutic strategies that will advance the care of patients with neuroendocrine tumours.”

Through this study, researchers sought to understand both the tumours themselves and the surrounding cells in the tumour microenvironment.

Leveraging single cell sequencing allowed for an unprecedented view of the genes and signalling pathways that are involved in tumour progression and potential response to immunotherapy. 

The team uncovered previously unappreciated heterogeneity within neuroendocrine tumour subtypes and revealed potential evolution in tumour characteristics as they metastasize. At that resolution, they were also able to observe cells and related proteins in that microenvironment that suppress immune responses. Targeting those proteins could render these tumours more responsive to immunotherapy treatment.

Source: Boston Medical Center / DFCI

Article: Intertumoural lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumours