The current cancer therapies and drug design strategies developed are more precisely aimed at targeting the cancer cells. Primary challenge in selectively targeting cancer cells is to differentiate between the cancer cells and the normal cells. One such difference is enzyme telomerase activity which has been an exciting drug target as it is active in almost 85—90% of all human cancers but is inactive in normal human cells. Telomerase is a ribonucleoprotein that synthesizes telomeres. The increase in the activity of telomerase is seen very early during tumorigenesis and techniques such as the telomeric repeat amplification protocol (TRAP) assay have been useful in measurements of telomerase activity.
Molecular targets for Telomerase Inhibition
There are multiple molecular targets discovered in past towards telomerase based anticancer approach. The approaches have been directed at inhibiting all aspects of telomeres or telomerase biology through immunotherapy vaccines targeting telomerase, human hTERT-specific epitopes. It inhibits the transcriptional and translational activation of hTERT. Oligonucleotide and small molecule is regarded as one of the standard pharmacological approach where oligodeoxynucleotides are developed complementary to the hTERT mRNA leading to rapid cancer cells death by obstructing the telomeres structure. Suicide gene therapy is an extremely effective advancement where hTERT promoter-driven expression of a toxic gene restricts the expression of the tumors. Other approaches include telomerase disrupting agents such as G-quadraplex stabilizing molecules and antisense ribozyme or small interfering RNA agents targeting TERT mRNA or hTR.
Current Pipeline Scenario- A Graph Representation
Telomerase Inhibitors in Pipeline and Major Players
In recent years, two major biopharmaceutical companies Geron and KAEL-Gemvax (South Korean company) have established themselves as pioneers in telomerase inhibition approach. Since there are no telomerase inhibitors have been approved, these two companies may lead in providing the breakthrough. KAEL- Gemvax’s vaccine GV1001 has approached NDA after successful phase III study for pancreatic cancer. The company strongly believes in their lead drug candidate GV1001 as blockbuster potential and currently the most advanced therapeutic cancer vaccine in development targeting telomerase inhibition.
Geron Corporation relies heavily on their lead drug candidate molecule Imetelstat as telomerase inhibitor. In past Geron has witnessed several failures with stem cells therapies and cancer treatments thereby discontinued its all stem cell operations in 2011 and sold it to BioTime’s subsidiary Asterias Biotherapeutics. Geron is currently targeting the market of myelofibrosis which is dominated by Celgene, Novartis, and Incyte, although they don’t have dedicated treatments. So, this represents a major opportunity for imetelstat. Several types of cancers are being targeted using telomerase inhibitor which represents a major inclination and interests of these firms to establish in market.
Other companies coming up in the market with telomerase inhibiting drug candidates include Adamis pharmaceutical corporation and Oncolys Biopharma which are currently testing their drugs in clinical trials stage. With few companies reaching the clinical trial development stage and multiple cancers under investigation, telomerase inhibition remains a striking and useful target in future for biotech and pharmaceutical companies with multiple opportunities of escalation.
Written by Tarun Jain, Associate Analyst at DelveInsight
Report: Telomerase Inhibitors-Pipeline Insights, 2015
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