Therapeutic strategies that block Cytotoxic T lymphocyte antigen-4 (CTLA-4) enhance antitumor immunity and prolong the lives of patients with metastatic melanoma. However, only a subset of patients benefit, and responses are often delayed due to heterogeneous response kinetics. ...
Cancer vaccines are designed to activate an immune response to tumor-specific or tumor-associated antigens expressed by the tumor. Cancer vaccines take many forms, including synthetic peptides, tumor cells and lysates, cell lines, and autologous antigen presenting cells like den ...
Melanoma is the third most common skin cancer but accounts for the majority of skin cancer-related mortality. The rapidly rising incidence and younger age at diagnosis has made melanoma a leading cause of lost productive years of life and has increased the urgency of finding improved adjuvant t ...
V600BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression. Despite the fact that BRAF inhibitors (BRAFi) can elicit anti-tumor responses in the majority of treated patients and confer ove ...
Personalized melanoma medicine has progressed from histopathologic features to serum markers to molecular profiles. Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorp ...
The standard of care of patients with malignant melanoma is dramatically changing, hallmarked by the approval of three new agents for the treatment of malignant melanoma in 2011. In this changing therapeutic landscape, several clinical issues are emerging which will best be addressed th ...
Melanoma is a main example of how applying advances in basic biology, pharmacology, and molecular diagnostics into the clinic results in unprecedented benefits to patients. After many years of lack of advances in the treatment of patients with metastatic melanoma, the advent of new therapi ...
The growth of new blood vessels, known as angiogenesis, is a dynamic but highly regulated process involving many different regulatory pathways. Endothelial cell migration and proliferation is also essential for this process to occur. Studying the behavior of endothelial cells and how t ...
Neoadjuvant therapy is therapy administered before surgical intervention and while the tumor remains in the breast. It may be given to treat large, locally advanced tumors, with the aim of shrinking them and thus making their surgical excision either simply possible or less radical. Most neo ...
If breast cancer patients are not cured, it is largely because of the fact that the cancer has spread beyond its primary site—the breast—to distant sites, such as, e.g., bone marrow, lung, brain, and/or liver. These secondary tumors are called metastases, and the underlying mechanisms leading to these ...
The aim of our lab is to understand the contributions made by cell adhesion molecules in the processes of disease. Much of our recent work has focused on the role played by β3-integrin in mediating pathological angiogenesis. It is fair to state that without the ability to manipulate the mouse genome, and ...
Estrogen receptor (ER)-positive MCF-7 breast cancer cell lines can be used both in vitro and in vivo to create anti-hormone resistance. Estrogen withdrawal in vitro results in spontaneous growth of MCF-7 cells. Similarly, culture in the selective ER modulators (SERMs) tamoxifen and ralox ...
Phospho-specific antibodies have become very useful reagents for study of signal transduction pathways. This chapter describes the production of phospho-specific antibodies and their use to assess individual phosphorylation events in vivo in cells. The first step involves the s ...
For cellular-invasive processes during a variety of physio- and pathophysiological events, including cancer, a fine-tuned balance between the formation and loosening of cell adhesive contacts has to occur, implicating the action of pericellular proteases; among those, the serine ...
The analysis of gene expression patterns by filter-based complementary (c)DNA microarray remains an important technique in the molecular biology laboratory, despite the development of large-scale cDNA microarray analysis (see Chapter 27). This chapter provides an overview of t ...
The tumour suppressor gene, TP 53 (commonly also called p53) has multiple, important cellular functions involving control of apoptosis, downstream cell cycle regulation via p21 and cyclin dependent kinases, and control of tumour angiogenesis. Somatic mutation of TP 53 is considered to be ...
The measurement of the expression of hormonally regulated genes in breast cancer may provide an indication of its hormone responsiveness. In addition, these genes may provide novel therapeutic targets. This chapter reviews the hormonally responsive genes that have been identified ...
A robust ribonuclease protection assay is described here. In brief, total cellular RNA, carrier yeast transfer RNA, and 32P-labeled antisense riboprobes, (one or more designed to detect the RNA species being studied and another to detect a suitable RNA species to act as a loading control) are com ...
This chapter describes methods that allow researchers to localize sites of gene expression at both the mRNA and protein levels, within a histological section of a single tissue or tissue microarrays. Identification of the cells within a tumor specimen that express a specific mRNA (assessed ...
Fluorescence in situ hybridization (FISH) is increasingly recognized as the most accurate and predictive test for both HER2 gene amplification or expression and response to Herceptin™ therapy in breast cancer. Diagnostic procedures for FISH require rigorous quality control, as wi ...

