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Breast cancer, with its ever increasing number of victims, has become a potential target for the pharmaceutical industries. Fear, pain, stigma and a lot of other such words have associated with breast cancer. The possible cures including chemotherapy with hair loss or surgeries with breast amputation are even horrible to think about. There is undoubtedly a strong need to develop better screening methods for early diagnosis as well as efficacious drugs that can selectively kill the target cells without awful side effects. High throughput screening shows a ray of hope in this context. It is a robust and pragmatic approach towards the designing of newer and better drugs that can selectively target cancer cells. Genes Involved in Breast Cancer As many other types of cancer, breast cancer also involves the abnormal and uncontrolled of cells. This uncontrolled growth of cells may lead to the formation of tumors that can metastasize in chronic stages. Such cancer occurs due to mutations in some critical genes which result in unchecked division of cells. BRCA1, BRCA2, CDH1, PTEN, STK11, TP53, AR, ATM, BARD 1, BRIP1, CHEK2, DIRAS3, ERBB2, NBN, PALB2, RAD50, RAD1 are the major genes which are linked directly or indirectly in the onset of breast cancer. Most of the breast cancers are not inherited. However, two breast cancer related genes (BRCA1 and BRCA2) have found interesting position in the context of medicinal research because they are responsible for hereditary breast cancer [1]. Of these genes BRCA2 is known as tumor suppressor gene. As the name indicates the protein produced from BRCA2 helps to suppress tumor growth in normal cells. BRCA2 interacts with various other proteins in the cell and helps to repair damaged DNA. The mechanism of action of BRCA2 is elaborated in the following figure which shows the interaction of BRCA2 with RAD51, BRC1-4 and other proteins in order to repair damaged DNA [2]. Breast Cancer Cells are deficient of BRCA2 About 800 mutations in the BRCA2 gene have been identified that result in nonfunctional versions of this gene. When this gene is absent in the cells, the process of repair of damaged DNA cannot take place. This leads to the accumulation of defected DNA in the cells that causes the cells to divide abnormally resulting in the formation of tumor. High Throughput Screening for BRCA2 A variety of compounds like imatinib, sorafenib etc. are used in HTS for screening cancer samples. The fact that BRCA2 protein is absent is absent in cancer cells provides an opportunity to selectively target only cancer cells for cancer therapy. As the BRCA2 deficient cells lack the DNA repair system, they are hypersensitive to ionizing radiations and DNA cross-linking agents. Various drugs including olaparib and cisplatin have been developed to target the BRCA2 deficient cells. In another study, marine natural products libraries were used for phenotypic-selective high throughput screening of BRCA2 deficient cells. These compounds were derived from marine organisms including Plakortis quasiamphiaster (Palkinidine family) and Crella spinulata. Palikindines are DNA intercalating agents that show cytotoxicity in BRCA deficient cells. Palkidines intercalate DNA and damage it. BRCA2 deficient cells retain this intercalation of DNA as they have defective repair sytem. In this study, samples were taken from the screening plates and incubated with a negatively supercoiled DNA. Samples were then run on agarose gel followed by ethidium bromide staining. If there is intercalation between DNA bases there will be a reduced superhelicity in the plasmid DNA. This sort of assay is very simple and allows rapid identification of lead compounds in the libraries [3]. Conclusion In a nutshell, BRCA2 is very important gene related to the onset of breast cancer. As this gene is linked to the inheritance of breast cancer as well, there is an ardent need to develop more and more high throughput screening assays for this gene. Virtual screening and computational approaches can also be used to broaden the frame of chemical libraries. Other assay approaches related to this gene will be discussed in near future on this blog! We has established long-term and stable relationships with more than 10,000 customers from pharmaceutical and biotech companies, universities and research institutions. We have high quality inhibitors like Ostarine, mk-2866, GSK1120212 & more. We have headquarters in both United States and Europe, and also has 38 distributors worldwide. We provide overnight delivery in North America and Europe.
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