Targeted therapeutics for non small cell lung carcinoma
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] "Lung carcinoma, also known as lung cancer, is a malignant tumor of lungs characterized by uncontrolled call growth in lung tissue. Tobacco smoking is the reason for nearly 85% of cases of lung cancer. The rest 10-15% are usually a combination of genetic factors, secondhand smoke, environmental pollutants, asbestos and radon gas exposure. Chest radiography and CT scan with confirmation by biopsy are the ways to detect the cancer. The type of cancer, degree of spread and the overall health weigh in on the outcome and eventual possible cure. Still now, most cases are not curable. Surgery, chemotherapy and radiotherapy are the treatments of choice for all types of lung cancer. Being the most common form of cancer in men and second most common form in women, after breast, data of the year 2012 showed 1.8 million incidences of lung cancer resulting to 1.6 million deaths worldwide, with the most common age of diagnosis being 70 years. 5-year survival rate in USA is 17.4%. ... Studies has been done to unravel the downstream effect after knocking down the oncogene via siRNA(42). Malignant cells have a number of secondary pathways, along with the primary pathway, which remain dormant till the disruption of the primary pathway(43). A complex mechanism controls this function which is triggered by the change in downstream protein and gene expression levels. This makes the cancer cells develop drug resistance(44). In this project, we developed a gelatin-based nanoparticle (GelNP) that will act as a vehicle to deliver targeted siRNAs against NSCLC cells in combination with Cisplatin. The cetuximab (Ab), an EGFR targeting antibody, shall be attached to the surface. The AXL and FN14 SiRNAs shall be conjugated to the antibody by the thio-ether linkage. The cetuximab antibody shall be used to specifically target the cell and also to protect the siRNAs from degradation. We predict that 146kDa cetuximab antibody will shield the 15kDa siRNAs and prevent it from exposure to environment. Since AXL and FN14 has been observed to be related to EGFR, we hypothesize that knocking down AXL and FN14 will block EGFR and thus allow the TKI to continue its course of therapeutic action."--Introduction.
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