Although clinically well tolerated and effective, existing cancer therapies are expensive and have long term side effects. The cost of some chemotherapy and immunotherapy infusions is three times the average monthly income of the American full-time salary workers. Therefore, improved cancer targets are being actively under intense investigation.
A new era of gene therapy is in progress for the possibility of a cure for cancer. Scientists are trying to introduce genes in tumours via genetically engineered vectors (adenovirus, retrovirus). The tumour cell surface antigen is being matched with a vector for successful acceptance and adsorption. However, identifying new targets to improve existing therapies could generate higher expectations. Few studies have indicated that the telomere is the Achilles’ heel of cancerous cells, as it serves to protect the chromosome from end-to-end fusion and/or degradation (chromosome instability). Much like a shoelace tip, the telomere is located at the end of a chromosome and consists of tandem DNA repeats, whereas telomerase is the associated enzyme which helps to replicate the telomeric end. The telomerase is turned off during normal cell division, resulting in senescence (cell division halted) or apoptosis (cell death). However, cancerous cell lines maintain the telomere length and therefore, can divide indefinitely. Interestingly, alterations in telomerase activity utilizing a modified telomerase enzyme or antisense oligonucleotides in various cancer cell lines have resulted in apoptosis or differentiation (potency for cell division halted). Therefore, telomerase inhibition could be a potential strategy for cancer treatment.
Telomerase based treatments
Telomerase inhibitors
However, telomerase inhibition based treatments are being designed by various groups of scientists. The program mainly includes telomerase inhibitors, telomerase vaccines, and engineered oncolytic viruses. Briefly, telomerase inhibitor is an oligonucleotide, which is also called GRN163L. It directly binds with the active site of telomerase and therefore inhibits its activity. After that, the enzyme cannot replicate the telomeric end of cancer cells anymore, which halts the cell cycle. This therapy is already successful in lung, breast, prostate, and liver cancers at culture levels and work is in progress for animal studies.
Telomerase vaccines
Tumour-associated antigens to develop immunity against tumour exists in both human and animal models. Unfortunately, these antigens are very specific and vary for types of cancer and even immunity of an individual. Therefore, the target for vaccine preparation is uncertain today. However, studies claim that telomerase could be the universal target, as expressed in the majority of cancer cells. Earlier, clinical trials for vaccine formulation on human telomerase reverse transcriptase (the catalytic subunit of telomerase) results in specific immune responses. Hence, a broad spectrum second-generation vaccine is highly possible.
Oncolytic virus
Another strategy includes the oncolytic virus, which kills cancer cells by oncolysis. The direct destruction of malignant cells also requires specific genetic or epigenetic targets present only in such cells. The modern genetic engineering research is now designed using telomerase specific gene with a viral vector. The construct is designed so that only telomerase (hTERT) could express this promoter, which finally leads to selective viral replication and oncolysis of the cell. This strategy has already recorded several milestone achievements, and this could be particularly useful for internal organ tumour treatment where surgery is not easy.
Conclusion
In summary, the study revealed that telomere indeed could be a new and improved target for cancer treatment. However, this field is progressing considerably and is rapidly gaining medical and scientific acceptance. As many technical and conceptual problems are yet to be solved so research still needs to focus on telomerase inhibitors, telomerase vaccines and engineered oncolytic viruses are promising candidates for the treatment of human malignancies.
