The human body has been designed in a way as to sustain itself in adverse situations, however many of our gene variations aren’t required on a daily basis, these genes and their consecutive amino acids produced are therefore shut down either by translation gap (preventive step), or the inactivation of the amino acid produced (reactive step). The amino acids are inactivated by phosphorylation of the amino acids, done by the protein kinase enzymes. Protein phosphorylation rids the body of proteins which are otherwise unnecessary, but during trouble, can be of immense value in restoring the balance of the body. Cancer is one such instance, wherein the body goes on uncontrolled replication of cells (Tumor). These proteins if present in active mode can act as regulators of cell death or control cell growth, hence activation of these proteins remain critical. This is done with the help of protein kinase inhibitors. These protein kinase inhibitors block the protein kinases and enable the action of these essential proteins, thus aiding in the regulation of cancerous cells.
Phosphorylation is done usually with the help of ATP (adenosine triphosphate). Kinase inhibitors can either act as a competitive inhibitor to ATP, the phosphorylating area, the enzyme substrate, or by binding to the enzyme’s allosteric site (site required for indirect enzyme action). One of the key enzymes being targeted by various drugs is the Tyrosine kinase. Kinases are also essential to phosphorylate certain known serine or threonine residues, and those required for insulin regulation, hence drugs used to inhibit tyrosine kinase should not (in practice) inhibit these essential kinases. Therefore drug molecules designed, are generally of small molecular weight, which have higher specificity. Multiple kinase inhibitors therefore need to be small molecular sized, so as to hive higher specificity. They also need to have multiple specificities, so as to reduce negative drug interactions, which may be caused by introducing various classes of inhibitors. One such multi kinase inhibitor drugs is Dasatinib, which is a novel drug, and acts similar to nilotinib and imatinib (previous multi-kinase inhibitors) but works more effectively and requires reduced follow up of once in 5 months only.
Cancer as of today, still is incurable in their advanced stages, the possibility of extending the life of patients to at least a year or few is thus readily accepted by most of the patients. Most of the Multi-kinase inhibitor drugs are used for advanced cancer conditions, e.g. leukemia, lung cancer, colorectal cancer, prostate cancer, renal cancer, etc to name a few. The treatment doesn’t guarantee a cure but merely extension and a fractional possibility of complete remission of cancer. It is therefore an area of great curiosity and focus, as the cancer market is ever growing due to lifestyle changes and increasing population, along with evolving diagnostic/detection procedures.
However the inhibition of natural enzymes comes with a heavy price, “chemotherapy” as Multi-kinase drugs are commonly known, is harmful for the normal functioning of liver and critical organs like the kidney and the lungs. It is therefore taken with utmost care and notification is given to the patient about the adverse side effects. These inhibitors are therefore accompanied by various other regulators and sometimes even antibiotics, which again have a negative effect on the liver. Hence some patients are conscious about the same and prefer death by cancer.
The market overall, remains positive for kinase inhibitors, innovations in the field have already showed more than 85% success rate, although the issue for addressing adverse conditions remains formidable, the future does look promising. The largest market for these drugs remains in the United States and the North American region. This was followed by the European region and the Asia-Pacific region, the European region giving higher volume and the Asia-Pacific region showing higher growth rate, although government subsidies results in forced reduction of prices. The rest of the world region looks promising, and shall show a good growth in the forecast period.
Some of the major players in the research and manufacture of these drugs include: Pfizer Inc., C. H. Boehringer Sohn AG & Co. KG, Genentech, Inc., Bristol-Myers Squibb Company, AstraZeneca plc, GlaxoSmithKline plc, Novartis International AG, etc, to name a few.
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