“The most effective cancer therapies are targeted to cancer-causing mutations.”

The paper has two major results with significant implications for lung cancer treatment in particular and, more broadly, for the development of new cancer treatments and the design of therapeutic cancer clinical trials.

The major results are:

1. Mutations in the epidermal growth factor receptor gene (EGFR) are common in lung cancer.
2. The presence of EGFR mutations correlates with, and almost certainly explains, a significant proportion of the clinical responses to EGFR inhibitors such as gefitinib (Iressa™).

The implication for lung cancer treatment is that patients with EGFR mutations should probably be treated with EGFR inhibitors such as Iressa™ or Tarceva™ (erlotinib) as part of their treatment. The findings suggest that patients with EGFR mutations should be treated with Iressa™ or Tarceva™ as their initial treatment rather than chemotherapy as currently done and that clinical trials should be performed to determine whether this is indeed true.

The broader implications of the results are:

1. The most effective cancer therapies are targeted to cancer-causing mutations. This was previously shown in leukemias and gastrointestinal stromal cell tumors but this work is the first demonstration in one of the common solid cancers.
2. Different ethnic populations may differ in the frequency of specific cancer-causing mutations (EGFR mutations are more common in lung cancers from Japan than from the US) and these differences may impact on treatment results (gefitinib showed a higher response rate in Japan than in Europe or the US).
3. Genome-wide screening methods are a powerful tool for discovering cancer-causing mutations.
4. Clinical trials of targeted therapies should focus on the patients whose cancers carry the relevant mutations—thus genomic studies are a critical element in clinical trials.

As above, the new discovery is that EGFR mutations are common in lung cancer and are correlated with responses to Iressa™ and Tarceva™. This discovery will lead to routine testing of patients with lung adenocarcinoma to determine if they have mutations in EGFR.

Specific: Genetic changes in the EGFR gene frequently cause lung cancer. Patients with these mutations can be effectively treated with EGFR inhibitors such as Tarceva™ and Iressa™.

General: This is another example of an emerging paradigm: understanding the mutations that cause cancer will lead to the development and deployment of new cancer treatments.

We came at this study from two different angles. Bill Sellers and Matthew Meyerson are physicians and cancer biologists who were using the sequence of the human genome and genomic methods to look systematically for mutations in protein tyrosine kinases, expecting to identify new targets for cancer drug therapy. Bruce Johnson is a lung cancer physician and researcher who was interested in understanding the dramatic but rare clinical responses to gefitinib in a subset of lung cancer patients.