During the recent years scientists have discovered more details about cellular genomes, gene mutations and mechanisms involved in cancer development and spreading. This led to hopes that soon there will be more targeted cancer therapies which will be more efficient and less toxic. But this is not happening yet?
The main challenges are cost and time and also difficulties to identify potent, selective drug-like inhibitors for majority of cancer mechanisms. For example, RAS family of oncogenes is known to a long time for its involvement in cancer, however there are still no targeted inhibitors. Another examples are non-coding RNAs which were shown to have important role in many diseases including cancer, and yet it is very difficult to create traditional targeted inhibitors against them.
The opportunities of antisense therapies
Antisense therapies used the well-established Watson-Crick hybridization rules and could be used to alter RNA metabolism. Targeting RNA could be more efficient than targeting proteins which often have multiple homologous family members. Another advantage is that antisense drugs do not change significantly their properties from one drug target to another.
Recent developments in antisense therapies
Some of the targets of antisense therapies are liver genes. In some cases, the RNA drugs were able to nearly completely remove liver derived protein from the plasma. Another organ which was a target of antisense therapies is kidney. Central nerve system is another target of antisense therapies. Surprisingly muscles have shown to be also a very good target for RNA therapies and there are studies exploring their usage in myotonic dystrophy.
However, targeting outside the kidney and liver has proven difficult due to various reasons like short live of RNA, limited potency and difficulties to target the cell RNA. Recent studies have shown that not all cell RNAs are sensitive to the antisense therapy.
Majority of the current antisense therapies use the RNase H mechanism. Clinical experience in oncology is so far limited, however their application is under investigation in prostate and lung cancer. Recent glioma study has shown increased survival rates in patients treated with antisense therapies (39.1 months) in comparison to standard chemotherapy (21.7 months).
In conclusion while it is still early to assess the benefits of antisense therapies due to limited clinical experience there is clearly a potential in them. In the future antisense technologies could be used to target drug resistant mutations and personalised therapies which target patient specific mutations. They could also be used to target specific pathways which are currently difficult to alter.
Source: Antisense therapies for cancer: Bridging the pharmacogenomic divide
Author: Olga Peycheva
Olga is a clinical research professional who has been working in clinical research since 2005. She has extensive experience in clinical research in Eastern and Western Europe.
Originally published on 7 July 2020
