Researchers evaluate survivin expression in neuroendocrine tumors

Reviewed by Emily Henderson, B.Sc.Jun 10 2020

Volume 11, Issue 23 of @Oncotarget reported that tissue microarrays of 132 patients were stained for survivin using immunohistochemistry and correlated with outcomes.

Using a genomic database, the authors then correlated survivin mRNA expression with the radiosensitivity index in 52 samples of Neuroendocrine tumors. Finally, they studied the effect of radiation on survivin expression in human cell lines and the impact of knock-down of BIRC5 on cell proliferation and radiation sensitivity.

The authors found that survivin positivity by IHC correlated with shorter survival.

Radiation exposure increased BIRC5 gene expression in a human carcinoid cell line.

Survivin expression in Neuroendocrine tumors correlates with an inferior survival and survivin expression in human carcinoid cell lines increases after exposure to ionizing radiation.

Neuroendocrine tumors (NET) are a heterogeneous group of neoplasms that arise from neuroendocrine cells or their precursors."

Dr. Renuka Iyer, Department of Medicine at Roswell Park Comprehensive Cancer Center in Buffalo, New York

NET can occur throughout the body but is mostly associated with the digestive or bronchopulmonary systems.

Classification of NET ranges from well-differentiated neuroendocrine tumors to poorly differentiated neuroendocrine carcinomas based on their morphology and histological grade assessed by the Ki-67 proliferation index or a number of mitoses per 10 high-powered fields.

Tumors that progress on first-line therapies has limited systemic options that include cytotoxic chemotherapy, molecularly targeted therapy, interferon- and more recently, peptide receptor radioligand therapy.

To test the potential of survivin as a prognostic marker and therapeutic target the authors evaluated survivin expression in NET and correlated it with clinical outcomes using annotated tumor tissue microarrays from patients with NETs. To better understand the role if any survivin in NETs of lung origin, using a genomic database the authors correlated the survivin mRNA expression with sensitivity to radiation using the validated radio-sensitivity index.

Finally, to determine if survivin targeting may increase response to radiation, the authors assessed change in survivin expression in a pulmonary carcinoid cell line in response to radiation and effects of survivin knockdown using si RNA on cell proliferation and radiation sensitivity.

The Iyer Research Team concluded in their Oncotarget Research Paper that these observations led to attempts at creating a vaccine that can trigger a stronger immune response against survivin.

Several vaccine approaches targeting survivin have been evaluated in clinical or pre-clinical studies, including dendritic cell vaccines, DNA vaccines, and peptide vaccines, with variable responses.

More recently, researchers at Roswell Park developed a survivin long peptide-mimic vaccine, Sur Vax M, that was shown to generate survivin-specific immunological response through activation of CD8+ CTL as well as CD4+ helper T cells.

Based on the safety and efficacy signal of this vaccine in malignant gliomas that are survivin positive by IHC and our finding of survivin being a prognostic marker and present in NETs, the authors find survivin to be a potential target in NET and have begun a pilot trial of Sur Vax M in survivin expressing NETs. Its association with RSI makes it an attractive candidate to be targeted using combination strategies using PRRT upon completion of further preclinical studies testing Sur Vax M, survivin antibodies and CAR T-cell approaches to guide optimal therapy and sequencing schedule.