John M. Kirkwood, MD

John Kirkwood, MD, PhD, discussed considerations for treating patients with melanoma using immunotherapy and how to properly monitor responses.

Each year, nearly 60,000 new cases of melanoma are reported in the United States. The vast majority of these are cured by surgery. However, 8,000 of these patients are found to have metastatic melanoma beyond the scope of surgical cure-and this number closely approximates the annual number of deaths from this disease. This statistic illustrates the lack of progress that had been made in the treatment of advanced melanoma over the last several decades.

The integrins are a family of transmembrane receptors important for the cell-cell and cell-matrix interactions that relate to processes of cell adhesion, migration, invasion, angiogenesis, and survival.

Integrins play an important physiologic role in cell adhesion, and accumulating evidence suggests that they also regulate cell growth, proliferation, migration, and apoptosis. A number of congenital and acquired disease states have been associated with integrins, and small- molecule integrin inhibitors have been approved for treatment of benign hematologic diseases. In cancer, aberrant expression with normal functioning rather than dominant genetic variations of genes coding for integrins has generally been observed. This aberrant expression is mediated through "bidirectional" receptor signaling and interaction with corresponding signals from growth factor signaling pathways, leading to inhibition of apoptosis, induction of cell proliferation, extracellular matrix remodeling, migration, and angiogenesis. From a clinical perspective, a growing number of molecules targeting integrins have been developed for treatment and imaging purposes; clinical studies in melanoma, prostate cancer, and other malignancies are underway. This review summarizes the biology of integrins, the signal transduction pathways they regulate, and their role in different stages of carcinogenesis. Furthermore, it provides a synopsis on the clinical advancements in integrin targeting for therapeutic and imaging purposes in cancer.

Melanoma incidence and mortality continue to rise unabated in older individuals. Early clinical detection should take into account the different subtypes.

The rigorous assessment of thebenefits of radiotherapy formelanoma has been confoundedby superstition on one hand, andreligious fervor on the other. In thisissue, Ballo and Ang have reviewedthe use of radiotherapy for melanoma,focusing primarily on the controversialtopic of adjuvant postoperativeradiotherapy to the primary tumor bedand regional lymphatics.

Melanoma is almost 100% curable when diagnosed early, but when metastatic to distant organs, it is associated with a poor survival. The interferons have shown the most promise in the treatment of melanoma and interferon

Any new medical textbook must compete for readership under new rules. It is not just the numerous other books being published but also the wealth of information on the Internet that vies for the time and attention of the inquiring reader. Web-based general search engines and medical literature tools have made the previous frequent trips to the hospital library nearly obsolete for many of us. There is ready access to original references or discussion about almost any topic in cancer care. A successful book on cancer treatment, therefore, must provide more-something unique for the practicing physician, student, or teacher. Ideally, it will present a useful synthesis, interpretation, and, with luck, clinical wisdom