Charles M. Rudin, MD, PhD

Lung cancer remains the leading cause of cancer-related death in the United States. Ongoing research into the molecular basis of lung cancer has yielded insight into various critical pathways that are deregulated in lung tumorigenesis, and in particular key driver mutations integral to cancer cell survival and proliferation.

Calendar age and biological age do not always correspond. Pablo Picasso, source of the quote that begins the title of this commentary, lived a notoriously robust and active life through his later decades, dying in his nineties in the midst of a dinner party. In the oncology community, with the advent of targeted therapeutics and better supportive care, the disparity between the two is likely to be increasingly relevant to both research and practice. In this issue of ONCOLOGY, Chiappori et al review data supporting the idea that even in the context of standard cytotoxic chemotherapy, elderly patients with advanced NSCLC experience similar response rates and similar survival benefits to those seen in younger patients. They note that biases excluding elderly patients from clinical trials result in gaps in our knowledge of how to best treat older patients.

Lung cancer is the leading cause of cancer death worldwide, responsible for over a million deaths annually. In the United States in 2009, it is estimated that 219,440 cases will be diagnosed and 159,390 deaths will be attributable to lung cancer.[1] The vast majority of these deaths are cigarette-smoking associated. However, an estimated 10% to 15% of these deaths will occur in “never-smokers.”

Small-cell lung cancer (SCLC) accounts for approximately 15% of the 215,000 new lung cancer diagnoses in the United States annually. With a case-fatality rate greater than 90%, SCLC will be the cause of over 25,000 deaths in 2008 alone.

The epidermal growth factor receptor (EGFR) promotes the growth of different cell types and has been implicated in tumorigenesis. The EGFR comprises a family of four structurally similar tyrosine kinases with a complex link to downstream signaling molecules that ultimately regulate key cell processes. Anti-EGFR agents have been developed as promising therapeutic anticancer targets, and some have been recently approved for the treatment of non-small-cell lung cancer and colon cancer. The two anti-EGFR therapies with the greatest clinical application are monoclonal antibodies that block the binding of ligands to EGFR and small-molecule tyrosine kinase inhibitors that inhibit the binding of adenosine triphosphate to the internal tyrosine kinase receptor of EGFR. We attempt to give an overview of the EGFR function and biology, focusing on the most important clinical findings and applications of EGFR inhibitors in lung and head and neck cancer.