Avastin is a“ recombinant humanized monoclonal IgG1 antibody“ (Drug bank, 2005) drug, It is created from the ovary of chinese hamester which contain “antibiotic gentamicin“ (Drug bank, 2005) and its molecular heaviness is 149 kilodaltons (Drug bank, 2005). Contains the structure of human part and determining part of mouse antibody that connect to human vascular endothelial growth factor( VEGF)(Dr Ananya Mandal, MD, 2014). Avastin used to treating several type of cancer such as colon, renal cell carcinoma,lung, and breast cancer and a particular eye sickness(Wikipedia). Colon cancer, the pathophysiology is mutation in a gene APC“adenomatous polyposis gene“(Tomislav Dragovich, MD, PhD, et al, 2017). APC encode a protein which is issential in “activation of oncogene c-myc and cyclin D1“ (Tomislav Dragovich, MD, PhD, et al, 2017) which leads to grow tumor, also “DNA methylation“(Tomislav Dragovich, MD, PhD, et al, 2017) which affect genetic equation leads to tumor growth (Tomislav Dragovich, MD, PhD, et al, 2017).The causes of colon cancer is genetic inheritance or the life style for example alcohol, obesity, red meat(Wikipedia).
. Lung cancer, the pathophysiology is producing a protein by a gene which cause the lung cancer, this protein have a role in cell developing, cell cycle, angiogenesis, recognition, cell death, developing of tumor and organiztion of immune system(Peter J. Mazzone MD and Humberto K.
Choi, MD, 2014).The common cause of lung cancer is smoking which affects DNA leads to damaging a protein which protect human from cancer(Cancer Research UK, 2016). . Breast cancer, occur when the cell can not stop dividing, normal cell divide then offensive to other cells and they die when it was no needed, So the cells preserves by many proteins and pathways such as“ PI3K/AKT pathway and RAS/MEK/ERK pathway“`(Wikipedia), but sometime the gene mutated along these preventive pathway that makes the cell not be able to die(Wikipedia).in several breast cancer PTEN protein switch on PI3K/AKT path that leads to mutation of the gene for the PTEN protein and cause cancer, which is normally should be switch off when the cell ready to die. Another mutation like BRCA1 and BRCA2 might be hereditary or gained after the birth related to the breast cancer(Wikipedia).
Also a large amount of estrogen can cause mutation(Pavani Chalasani, 2018).The life style like smoking, alcohol ,food, the genetics and the health status it may be causes of breast cancer(Pavani Chalasani, 2018). While Kadcyla it is antibody medication composed of cytotoxic agent DM1, monoclonal antibody and stable linker MCC(US health care professionals). Prevent enveloping of cancer cell by liking with HER 2 receptor and leads to suppressing PI3K/AKT pathway which is “cellular signaling“(US health care professionals).Kadcyla used to“metastatic breast cancer “(Wikipedia).metastatic breast cancer, the pathophysiologyis the cell diveide and grow inside the main tumor then the new cell “enters the bloodstream or lymph channels“`(Wikpedia) the cell needs nutrition to survive until it reach the secondary place which is microvasculature then aim at tissue and attack it. At the metastatic place spread the cancer cell so inner the secondary place they form “micrometastasis“(Wikipedia) then they form tumor .
The metastatic breast cancer is a stage 4 of breast cancer so that means when the therapy of breast cancer is ineffective so the cancer cell spread to the body and metastatic cancer occur (Tom Seymour, 2017). Both Avastin and Kadcyla are monoclonal antibody (Drug bank, 2005) and they work on a protein which cause a tumor and both drug have same aim which inhibit the cancer cell another similarity between both drug that both of them treat breast cancer(Dr Ananya Mandal, MD, 2014). Mechanism of actionIn order to grow cancer cell in the body it needs oxygen and nutrition by blood vessels, therefore the growth of tumors depends on the blood vessels. Vascular endothelial growth factor(VEGF) which is an indicative protein that support to produce a new blood vessels in a cancer cell leads to growth a tumor and spread it in a different part of the body through the blood vessels . On the endothelial cell VEGF connects the receptors to help the new blood vessels grow (Dr Ananya Mandal, MD, 2014).
So Avastin (Bevacizumab) inhibit the activity of vascular endothelial growth factor on the endothelial cell surface, controlling this protein helps to stop signaling and prevent growing of the new blood vessels leads to decrease the blood flow to the tumor that leads to contraction of the tumor and that make the cancer cell not grow and not spread to the body(Dr Ananya Mandal, MD, 2014). In contrast the Kadcyla(ado-trastuzumab emtansine,T-DM1 ) works by connecting to a particular protein called HER2, which have an essential role for developing a breast cancer, and then forming HER2-T-DM1 compound that ingress into the cell“via receptor-mediated endocytosis “ (Mark Barok, Heikki Joensuu, et al, 2014). As a result of protein retraction of the antibody in the lysosome which is portion of T-DM1, robust DM1 release because “ the non-reducible linker is stable in both the circulation and the tumor micro environment“Mark Barok, Heikki Joensuu, et al, 2014). After releasing from the lysosome, DM1 containing “metabolites“(Mark Barok, Heikki Joensuu, et al, 2014) suppress microtubule structure leads to cell death (Mark Barok, Heikki Joensuu, et al, 2014).gure (4)(Mark Barok, Heikki Joensuu, et al, 2014) connecting T-DM1 to HER2 on plasma envelope and form HER2-T-DM1 compound and leads to lysosome degeneration that ingress into the cell“via receptor-mediated endocytosis “ (Mark Barok, Heikki Joensuu, et al, 2014) and release of DM1 because of protein degeneration in the lysosome and (lys)-MCC-DM1 Intracellular lysine control “microtubule assembly“(Mark Barok, Heikki Joensuu, et al, 2014) leads to “mitotic arrest, apoptosis, mitotic catastrophe“(Mark Barok, Heikki Joensuu, et al, 2014) and also dmage intracellular signaling (Mark Barok, Heikki Joensuu, et al, 2014).
The similarity between Avastin and Kadcyla in their mechanism that both drugs are working on the particular protein which have an essential role for developing cancer cell but in a different way. That means Avatin inhibit the activity of (VEGF)(Dr Ananya Mandal, MD, 2014), and Kadcyla connect to the (HER2) to form HER2-T-DM1 compound which inhibit microtubule structure leads to cell death(Mark Barok, Heikki Joensuu, et al, 2014. So both drug have same aim which is death or stop rowing of the cancer cell.