1. Latest Advances in Chemotherapeutic, Targeted, and Immune Approaches in the Treatment of Metastatic Melanoma 
Darshil J. Shah, MD, MPH, Roxana S. Dronca, MD 
Mayo Clinic Proceedings 
Volume 89, Issue 4, Pages (April 2014)
DOI: /j.mayocp
Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

2. Figure 1
Mitogen-activated protein kinase (MAPK) pathway signaling in malignant melanoma leads to phosphorylation and activation of RAS, RAF, MEK, and ERK, a process that ultimately regulates the cell cycle, differentiation, and apoptosis. Mutated BRAF, which is 500-fold activated, stimulates constitutive signaling, proliferation, and survival, making it an excellent target for vemurafenib and dabrafenib. Trametinib inhibits MEK, situated downstream.
Mayo Clinic Proceedings  , DOI: ( /j.mayocp )
Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

3. Figure 2
Timeline depicting Food and Drug Administration (FDA) approvals and landmark clinical trials in metastatic melanoma. CI = confidence interval; HR = hazard ratio; N = number of patients randomized; OS = overall survival; PFS = progression-free survival; RR = response rate.
Mayo Clinic Proceedings  , DOI: ( /j.mayocp )
Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions

4. Figure 3
A, T-cell activation with positive co-stimulation. B, Cytotoxic T-lymphocyte–associated antigen-4 (CTLA-4) is a negative regulator of T-cell activation. Inhibitors of CTLA-4 bind to CTLA-4 and block the interaction of CTLA-4 with its ligand, B7. Blockade of CTLA-4 augments T-cell activation and proliferation. C, Engagement of programmed cell death protein 1 (PD-1) expressed on T cells with programmed cell death ligand 1 (PD-L1) expressed on antigen-presenting cells (APCs) or tumor cells results in T-cell suppression and tumor protection. Blockade of this interaction with either PD-1 or PD-L1 blocking antibodies can “wake up” exhausted T cells, resulting in a T-cell response against tumor. MHC = major histocompatibility complex; TCR = T-cell receptor.
Mayo Clinic Proceedings  , DOI: ( /j.mayocp )
Copyright © 2014 Mayo Foundation for Medical Education and Research Terms and Conditions