The Potent Anticancer Drugs: Vincristine and Vinblastine
With the growing incidences of cancers worldwide, many cancer researchers are finding ways to combat this deadly disease. Also, scientists from all over the world have joined hands for the development of cancer drugs to be administered to cancer patients prolonging their survival. A drug takes several years to reach to the market passing through the various stages of approval. There are at present three main stages of development a drug has to pass, this includes the preclinical, clinical, and post-clinical research. Discovery of new cancer drugs may take place in three different ways: First include the accidental discovery, such discoveries are rare, the second include the discovery of anticancer drugs from the plants, fungi, and animals. While the third includes the study of cancer cells and developing a drug accordingly so that it can inhibit its growth process, leading to the cancer cell death. Moving on to the topic of interest, vincristine and vinblastine, which are the potent anticancer drugs for the treatment of certain cancers which include leukaemia, Hodgkin's and non- Hodgkin's lymphoma, thyroid cancer, brain tumour, advanced stage testicular cancer, and advanced stage breast cancer among the treatment of other cancers as well. These are obtained from the well-known plant Catharanthus roseus, the “sadabahar” plant in Hindi language. Vincristine and Vinblastine are known as clinic alkaloids, known as vinca alkaloids, alkaloids in plants, byproducts of the plant metabolism, play a significant role in providing protection against insect or animal attacks. This property of the alkaloids is exploited for providing protection against diseases in the form of drugs.
The anti-leukaemia drug, Vincristine is in demand, but has a very low yield from the source plant in comparison to the Vinblastine which is more than 1000 times in yield. This has however affected the price as well, the one with lower yield and high demand leads to being highly expensive. Whereas on the other hand, the Vinblastine costs one third of the Vincristine. Hence, to avoid high price, Vinblastine is being used as a parent drug for obtaining Vincristine via structural modifications.
Keeping in view the high price of the above-mentioned drugs, researchers moved on to experimentation with the extraction of these life-saving drugs from the plant-associated fungi. Hence, by the identification of fungi strain for the production of vincristine and vinblastine, the drugs were purified by using Thin Layer Chromatography (TLC) and HPLC, further characterized using UV-Visible spectrophotometer, ESI-MS and H NMR.
The mechanism of action of these drugs against cancer cells include the binding of the intercellular tubulin, in tumor cells, vincristine and vinblastine act by inhibiting the DNA repair and RNA synthesis mechanisms and blocks the DNA-dependent RNA polymerase.
With the generic name, vinblastine, this is available in the market by the brand name, Velban. The trade names for vincristine consist of Oncovin ®, Vincasar Pfs ®. Alternate names include, Vincristine Sulfate, LCR, VCR. These drugs are administered into the patient’s body through IV injection and are well-tolerated. However, some patients may experience discomfort in the form of side effects. At the time of dosing, the nurse or the medical personnel giving the medication must be trained in advance. This is due to the fact that the Vincristine is a vesicant, and may cause severe tissue damage and blistering in case of being escaped from the vein.
The global incidence of leukaemia according to the WHO analysis is higher in males with male to female ratio equal to 1.4. The prevalence is higher in Australasia, Australia and New Zealand, followed by the North America, and Western and Northern Europe. The success rate for treating advanced stages of cancer by vincristine and vinblastine without damaging other organs is still a topic of concern. Efforts are being made in this direction where these drugs can be used in combination so that the side effects can be reduced. However, for the treatment of several haematologic and non-haematologic malignancies, the concept of combination therapies and antibody drug conjugates is being practiced widely in the form of research and in the form of treatments as well on the global level. The current focus is being laid on the targeted drug therapies for the treatment of cancers where only the cancer cells are killed while the normal cells are safe. Antibody drug conjugates do have the ability to differentiate between the cancer cells and the normal cells. This would definitely help a wide range of patients suffering from cancers and in future we would have safe medications for cancers as well.