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Full-Text Articles in Pharmacy and Pharmaceutical Sciences
Design And Synthesis Of Macrocyclic Peptide Braf-Wt Dimerization Inhibitors For The Treatment Of Metastatic Melanoma, Chad Mulloy Beneker
Design And Synthesis Of Macrocyclic Peptide Braf-Wt Dimerization Inhibitors For The Treatment Of Metastatic Melanoma, Chad Mulloy Beneker
Theses and Dissertations
In cases of metastatic melanoma, BRAF is frequently mutated to the V600E oncoprotein causing uncontrolled cell proliferation driven by the MAPK-ERK pathway. There are several BRAF inhibitors, such as vemurafenib, which are FDA approved, but patients treated with these Type-I kinase inhibitors frequently observe relapse under mutant RAS and BRAF-wt conditions due to paradoxical activation. The mechanism of this resistance occurs through binding of the inhibitor to BRAF-wt initiating conformational changes which leads to BRAF dimerization. Once in the dimerized state, the inhibited monomer induces allosteric transactivation of the second monomer. This drug-induced activation of BRAF in cells with mutant …
The Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill
The Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill
Pharmaceutical Sciences (MS) Theses
Cancer is an ongoing global pandemic which has caused a dramatic shift in research priorities. One of the most aggressive and difficult to treat has invariably remained metastatic melanoma. Although encompassing only 4% of overall skin cancer diagnoses, chances for recovery were slim until recent revolutionary development of immunotherapy adding to its regimen spectrum. This is due to its resistance to many standard-of-care treatment methods, along with its relatively high-metastatic potential. Within the past decade, eight new targeted and immune checkpoint inhibitors have gained FDA approval. The median life survival has increased significantly from 9 months to over 2 years …