ISI provides a large menu of neuroendocrine biomarkers so that patients can be monitored. Unlike traditional cancers, neuroendocrine tumors have variable presentation and can be indolent for years then suddenly present with destructive effect. One patient with a large tumor may not experience symptoms for many years while another patient with a small tumor may suddenly experience rapid disease prorgession. In addition, functional tumors overexpress hormones that produce further symptomology. Symptoms can remain very vague for years (eg. fatigue, food fear) but then suddenly cause life threatening effects such as bowel obstruction. Neuroendocrine tumors were traditionally considered rare but clinicians now think they are more common than previously thought and that many patients suffer symptoms as they go undetected. And unlike traditional cancers such as colon or breast adenocarcinomas, they have a much higher probability of recurring even after complete resection. In fact, clinicians advise patients that tumor recurrence within 10 years is more certain than not. ISI’s selection of biomarkers includes 5HIAA, which is a breakdown product of serotonin that is often overexpressed by Nets. Elevated levels of 5HIAA were traditionally found in urine that portended recurrence. ISI was able to develop a plasma 5HIAA test and establish that elevated levels in the blood also correlate with a growing or recurring tumor.
ISI is constantly exploring the use of new biomarkers and is currently investigating UCHL1, which shows potential for diagnosing highly aggressive neuroendocrine carcinomas and monitoring treatment response, potentially detecting early-stage disease with greater accuracy than traditional markers like Chromogranin A (CgA) alone; research is also focused on utilizing biomarkers like PD-L1 to predict immunotherapy response in specific neuroendocrine tumor subtypes, particularly in high-grade neuroendocrine carcinomas. PD-L1 (programmed cell death ligand 1) is a protein marker that can be expressed on tumor cells, and its presence is often associated with a more aggressive tumor behavior, indicating potential for poorer prognosis and suggesting a possible role for immunotherapy with PD-L1 inhibitors in certain cases, particularly in high-grade NETs where the expression is higher; however, research is ongoing to fully understand its clinical implications in this cancer type.
- Shiqin Liu , Timothy Chai , Fernando Garcia-Marques, Qingqing Yin, En-Chi Hsu , Michelle Shen , Angus Martin Shaw Toland, Abel Bermudez , Alifiani B Hartono, Christopher F Massey, Chung S Lee , Liwei Zheng , Maya Baron, Caden J Denning, Merve Aslan, Holly M Nguyen, Rosalie Nolley, Amina Zoubeidi, Millie Das, Christian A Kunder, Brooke E Howitt, H Tom Soh, Irving L Weissman, Michael A Liss, Arnold I Chin, James D Brooks, Eva Corey, Sharon J Pitteri, Jiaoti Huang, Tanya Stoyanova. UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas. Cell Rep Med. 2024 Feb 20;5(2):101381. doi: 10.1016/j.xcrm.2023.101381. Epub 2024 Jan 19.
- Milon Mondal, Daniel Conole, Jaya Nautiyal & Edward W. Tate. UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology. British Journal of Cancer volume 126, pages24–33 (2022)
- Abir Salwa Ali, Seppo W Langer, Birgitte Federspiel, Geir Olav Hjortland, Henning Grønbæk, Morten Ladekarl, Staffan Welin, Lene Weber Vestermark, Johanna Arola, Pia Osterlund, Ulrich Knigge, Halfdan Sørbye, Patrick Micke, Lars Grimelius , Malin Grönberg, Eva Tiensuu Janson. PD-L1 expression in gastroenteropancreatic neuroendocrine neoplasms grade 3. PLoS One. 2020 Dec 14;15(12):e0243900. doi: 10.1371/journal.pone.0243900.
- Woojoo Lee, Min-ju Kim, Younghee Choi, Hyunchul Kim. PD-L1 expression and patient outcomes in gastrointestinal neuroendocrine neoplasm: a meta-analysis. Transl Cancer Res. 2021 May;10(5):2210–2218. doi: 10.21037/tcr-20-3482.