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Current Scenario and Impending Options in Colorectal Cancer Targets


When I studied pharmacology my Professor defined chemotherapy as “thrashing up the patient with a cricket bat in the hope that you get the cancer on a winning streak”.

Chemotherapy has plentiful of benefits, but the adverse effects can be noxious. We pharmacologists call “off-target toxicity” where the drug agents will kill the healthy cells as well as cancer cells. Whereas, the novel, targeted therapies are often designated as “silver bullets”. In my view, the targeted therapies are heat-seeking missiles designed to find and attack cancer but leave normal cells alone.

The history of targeted therapies goes the way back to 1960, when the Philadelphia researchers identified a chromosomal abnormality in a type of cancer chronic myelogenous leukaemia (CML).Later it was named as Philadelphia Chromosome but the researchers have no clue. However, it triggered lot of questions like, How did it came? What did it do? Was it beneficial or harmful?

After some years of extensive research, the scientists identified that Philadelphia Chromosome made a protein called BCR-ABL that would develop CML. The CML is BCR-ABL dependent and it can’t survive without it .However, the non cancerous, healthy cells are BCR-ABL independent don’t rely on this protein. So, if scientists target to block the protein BCR-ABL it would stop the cancer cell from working and become inactive.

At last, in the early 20th century FDA approves “Gleevec” a drug that blocks BCR-ABL to treat the patients with CML. “Gleevec” tremendously increased the patient population five year survival from 30% to 89%.

Recently, Colorectal cancer (CRC) has a high impact on health scenario. It is accountable to 800,000 new incidents diagnosed annually throughout the world.

Although a number of treatment options are available for CRC patients, including surgery, standard chemotherapy with 5-fluorouracil (5-FU) based regimens, the targeted therapies gains more attention. The molecular therapies targeting different mechanism were as follows,

However, the above said targeted cancer therapy has lot of adverse effects and the overall colorectal cancer survival rates are also low.

So, is there any novel target therapy to decrease the side effects and improve the survival rates?

Yes. Recently neuropeptide research gaining more attention and one such type is gastrin-releasing peptide (GRP) involved in the proliferation, local invasion, metastasis and angiogenesis of many tumors including CRC. GRP belongs to bombesin (BN)-like peptide family and normally functions as a gastrointestinal hormone and neurotransmitter. However, according to oncology perspective, GRP blocks the growth and differentiation of various tumors including CRC. GRP receptors (GRP-Rs) are highly populated in human CRC and human CRC cell lines when compared with normal colonic epithelial cells. So, the scientists may develop a target approach based on the following mechanism,

Recently, the molecules RC-3095 and RC-3940-II have showed potent inhibitory activity on several experimental cancers including CRC in vitro and in mouse xenografts in vivo. Further, a Phase I clinical trial with BN/GRP antagonist, RC-3095 is currently under progress and may expect a favorable outcome.

In my opinion, there are various potential targets are available for chronic diseases like diabetes, rheumatoid arthritis, cancer etc. By identifying the potential therapeutic targets, the outcome of treatment can be improved and adverse effects can be minified.

Do you feel stagnate to derive research concepts?

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