Individualizing lung cancer treatment
State-of-the-art management of lung cancer includes individualized treatment as a means of optimizing care. Personalized genomic cancer care is the pinnacle of this approach, and has far-reaching implications for both the medical and surgical treatment of lung cancer patients.
There are various lung cancer subtypes based on mutation status that might warrant different treatment approaches, and genomic analysis through profiling can help inform clinical decision in the context of each individual. These spaces are rapidly evolving and a number of Mayo Clinic investigators are at the forefront of advancing these fields.
Molecular maps allow physicians to tailor more specific drug therapy — referred to as targeted therapy — on the basis of an individual's genetic makeup. Molecule-specific agents are designed to work against a specific aberrant molecular pathway. They are increasingly used in the treatment of lung cancer to enhance therapeutic efficacy and limit toxicity. Mayo Clinic researchers have perfected a tumor assay that can quickly identify 187 mutations from 10 oncogenes commonly altered in lung cancer cells.
Mayo Clinic utilizes a protocol for treating locally advanced disease in patients with mutations in the EGFR gene or the ALK translocation. Such patients can be treated in a neoadjuvant manner with targeted therapy. How best to combine targeted therapies with traditional treatment approaches, such as systemic chemotherapy and radiation therapy, is an active area of investigation at Mayo.
To date, the most therapeutically important mutations to identify in molecular mapping for optimized lung cancer treatments include:
Epidermal growth factor receptor (EGFR)
EGFR mutations are more common in women and those of Asian descent. Furthermore, an EGFR mutation is estimated to be present in approximately 10 to 15 percent of all adenocarcinomas but is present in nearly 50 percent of individuals with lung cancer who have never smoked.
The EML4-ALK gene fusion
Representative images of ALK rearrangement
The EML4-ALK fusion is present in approximately 3 to 6 percent of adenocarcinomas and is also more common in people who have never smoked. Mayo pathologists routinely perform a fluorescence in situ hybridization (FISH) assay that assesses the abnormal fusion between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK).
V-Ki-ras2 oncogene (KRAS)
In contrast to the tendency for EGFR gene mutations and EML4-ALK fusion to occur in those who have never smoked, KRAS mutations are more common in past or current smokers.
The three most commonly utilized targeted agents against EGFR mutations are gefitinib (Iressa), erlotinib (Tarceva) and cetuximab (Erbitux). For treatment of lung cancer with the EML4-ALK fusion, the drug crizotinib (Xalkori) is approved. Multiple other agents are in development or in clinical trials that target other genes such as PIK3CA, c-MET, and BRAF.