The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 8, 2013
What drugs are available that use molecular targeting for adenocarcinoma of the lungs?
Barbara Campling, MD, Medical Oncologist, responds:
"Targeted therapies" are pharmaceutical agents that have been designed to target and inactivate specific molecular pathways that are activated in cancer, as well as other diseases. The most dramatically successful targeted agent to date is "Gleevec," a small molecule that inhibits a specific mutant tyrosine kinase (an enzyme), which occurs in most cases of chronic myelogenous leukemia. This drug alone has resulted in a very significant improvement in the outcomes of this disease. Now there is tremendous interest in developing similar approaches to target molecular abnormalities in lung cancer as well as other solid tumors. Cases of "adenocarcinoma" of the lung are included in clinical trials of non-small cell lung cancer (NSCLC). Adenocarcinoma now comprises the majority of cases of non-small cell lung cancer (NSCLC) in North America. Molecularly targeted agents are designed to inactivate specific molecules, which are perturbed in cancer cells. For example, they may interfere with growth factors or their receptors, interrupt other molecular signaling pathways, or interfere with the blood supply of tumors. The types of agents that can do this include monoclonal antibodies, antisense oligonucleotides (which interfere with the translation of specific messenger RNAs into protein), or small molecular inhibitors of specific molecular targets.
A monoclonal antibody called Bevacizumab, which targets the vascular endothelial growth factor (VEGF) and interferes with the blood supply of tumors, has been shown to increase survival in select patients with metastatic NSCLC when combined with conventional cytotoxic chemotherapy. Another inhibitor of the epidermal growth factor receptor (EGFR) called erlotinib has also been shown to improve clinical outcomes, especially for patients with NSCLC with EGFR mutations. Some subgroups of patients appear to respond better than others to the drug. For example, response rates are higher in women, never-smokers, and those with adenocarcinomas, as these patients are more likely to harbor EGFR mutations than older patients with a heavy smoking history. Patients with EML4-ALK translocations, which are also more common among never – or light smokers, respond particularly well to a targeted agent called crizotinib. This drug specifically targets this fusion protein and can result in response rates of over 50% and a response or stable disease rates in approximately 9 out of 10 patients.
We are hopeful that these new targeted agents will be able to improve upon the current disappointing results of chemotherapy in the treatment of advanced NSCLC.