Volume 1, Number 1
Release date: May, 2006 - Expiration date: May 2007
Estimated time to complete activity: 1.5 hours
Educational credits: 1.6 contact hours
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The American Cancer Society projects that more than 200,000
women will be diagnosed with breast cancer in the United States
in 2006, and nearly one fifth of that population will die from this
disease. Breast cancer accounts for approximately 32% of all
female cancers and remains the second leading cause of cancerrelated
death in adult women (American Cancer Society, 2005).
Treatments for these tumors have traditionally been limited to a
combination of therapies (i.e., surgical removal, hormone therapy,
radiotherapy, and chemotherapy), which have numerous
adverse side effects. Recently developed targeted therapies
exploit specific molecular aberrancies that coincide with tumor
development. Although the targets of these agents are involved
in normal cellular processes, certain tumor cells are dependent
on these pathways, whereas most normal adult cells are not.
Thus, targeted therapies are more selective for tumor cells than
for normal cells. Targeted agents, such as trastuzumab
(Herceptin®) and more recently bevacizumab (Avastin®), have
shown synergism with traditional chemotherapeutic agents, and
addition of these agents to clinical protocols has significantly
improved treatment efficacy. This newsletter reviews the mechanisms
underlying the activity of these two particular targeted
therapies for breast cancer and discusses current clinical
research on their use in metastatic and primary disease. Case
study examples will follow, illustrating the clinical applications
of these novel agents in the treatment of patients with
breast cancer.
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CELL SIGNALING
In multicellular organisms, communication between individual
cells is critical for survival of the organism as a whole. Such
exchanges are most often in the form of extracellular signaling
molecules or chemical signals produced and secreted by neighboring
cells (paracrine) or cells in more remote tissues
(endocrine). These molecules relay vital information regarding
the needs of the body to specific cells in order to govern the
appropriate cellular changes.
The activities of various signaling molecules are wide-ranging (e.g., growth, proliferation, metabolic regulation) and are mediated through complex systems of proteins within the cell that transmit these signals from the extracellular environment to the appropriate intracellular targets, which thereby trigger functional alterations. Initiation of these systems usually begins with binding of the signaling molecule (ligand) to specific receptors on the cell surface. This binding activates the receptors, which, in turn, activate other intracellular signaling molecules in a cascade or chain-reaction-like manner resulting in stimulation of a particular cellular response.
In tumor cells, several signaling pathways (i.e., those involved in proliferation, survival, and migration) become aberrant or overactive (or both) due to mutations or increased expression of certain proteins in the signaling systems. This often leads to rapid, uncontrolled proliferation and enhanced survivability. Such cellular alterations are considered hallmarks of cancerous transformation. Accumulation of these aberrancies results in more malignant tumor cell phenotypes.
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