Authors: Yuming Li, Wenshu Lu, Jiarun Yang, Mark Edwards & Shisong Jiang
Survivin (SVN) is a member of the inhibitor of apoptosis (IAP) protein family that promotes cellular proliferation and inhibits apoptosis. Overexpression of SVN is associated with autoimmune disease, hyperplasia and tumours and can be used as a biomarker in these diseases. SVN is widely recognized as a tumour-associated antigen (TAA) and has become an important target for cancer diagnosis and treatment.
We reviewed SVN research progress from the PubMed and clinical trials focused on SVN from https://clinicaltrials.gov since 2000 and anticipate future developments in the field. The trials reviewed cover various modalities including diagnostics for early detection and disease progression, small molecule inhibitors of the SVN pathway and immunotherapy targeting SVN epitopes.
The most promising developments involve anti-SVN immunotherapy, with several therapeutic SVN vaccines under evaluation in phase I/II trials. SVN is an important new immune-oncology target that expands the repertoire of individualised combination treatments for cancer.
- SVN is found in multiple cellular compartments and in the extracellular matrix. Through activation of mitosis and inhibition of apoptosis, SVN promotes cell proliferation and survival.
- SVN is highly expressed in tumour tissues where it upregulates mitosis and enhances cell survival by downregulating apoptosis and cell death.
- SVN is a biomarker for tumour metastasis and progression and several clinical trials have demonstrated its value in cancer diagnosis and prognosis of tumour progression and metastasis.
- Clinical trials on small molecules to target SVN have not proved successful. One possible reason for this is that inhibition of SVN may lead to compensation mechanisms involving signalling by other IAP family members.
- In contrast, immunotherapies targeting SVN are starting to show significant potential. Strategies under evaluation include peptide vaccines, a recombinant overlapping peptide vaccine, dendritic cell-based vaccines and combination therapies.
- To avoid selection of tumour progression through expansion of SVN non-expressing clones, future treatments should target multiple tumour biomarkers in addition to SVN.