Gataparsen

Survivin is widely overexpressed in many forms of cancer and studies have related high survivin expression with poor survival rates. Although, there have been several attempts to target survivin, most therapeutics haven't shown substantial success in clinical trials therefore, authors wish to attract the focus towards many recent therapeutic innovations to target survivin.

Survivin plays an essential role in the cell cycle progression, apoptosis, cell stress response, drug resistance and angiogenesis therefore the prognostic and targeting benefits of survivin have been underestimated. An update on the current and existing therapeutic strategies implemented to target survivin is provided. Therefore, the reader will gain an insight into the recent patents targeting survivin. The review has emphasised on patents for quantification of survivin, survivin peptides as immunotherapeutics, application of survivin promoters, RNA interference of survivin, small molecules inhibitors of survivin and nanoparticles targeting survivin. The review also encompasses the survivin targeted therapeutics being implemented at clinical stages which include survivin targeted immunotherapeutics, peptide-based vaccines, antisense oligonucleotides and chemical inhibitors.

We reviewed recent patents based on preclinical anti-survivin therapies reported to date and it was concluded that gataparsen has been most widely used for anti-survivin therapy in clinical trials. It was also concluded that most therapeutic patents were focussed on development of natural anti-survivin therapeutics such as anti-survivin peptides or survivin anti-sense oligonucleotides in the recent years therefore, proving that natural proteins and nucleic acids has an upper hand over chemicals and synthetic drugs.

Chemoresistance is mediated, in part, by the inhibition of apoptosis in tumor cells. Survivin is an antiapoptotic protein that blocks chemotherapy-induced apoptosis. To investigate whether blocking survivin expression enhances docetaxel-induced apoptosis in patients with non-small-cell lung cancer (NSCLC), we compared the antitumor activity of the survivin inhibitor LY2181308 plus docetaxel with docetaxel alone. We used change in tumor size (CTS) as a primary endpoint to assess its use in early decision-making for this and future studies of novel agents in NSCLC. Patients (N = 162) eligible for second-line NSCLC treatment (stage IIIB/IV) with an Eastern Cooperative Oncology Group performance status of 0 to 1 were randomized 2:1 to receive LY2181308 (750 mg intravenously, weekly) and docetaxel (75 mg/m intravenously, day 1) or docetaxel alone every 21 days. CTS from baseline to the end of cycle 2 was compared between the two treatment arms. The mean (SD) tumor size ratio for LY2181308/docetaxel and docetaxel was 1.05 (0.21) and 1.00 (0.15) (p = 0.200), respectively, suggesting no significant improvement in antitumor activity between the arms. Because there was also no significant difference between the two arms for progression-free survival (PFS) (2.83 months with LY2181308/docetaxel and 3.35 months with docetaxel [p = 0.191]), both arms were combined. Using the combined arms, CTS correlated with PFS (PFS = 4.63 months in patients with decreased CTS compared with 2.66 months in patients with increased CTS), supporting its use in early decision-making in phase II studies.