NEW YORK (GenomeWeb News) – UCLA researchers reported today that they have identified proteins that may eventually act as biomarkers guiding advanced lung cancer treatment.
Researchers at UCLA’s Jonsson Cancer Center used enzyme linked immunosorbent assays to assess protein levels in lung cancer patients receiving a new combination drug therapy. The findings, published in today’s issue of the Journal of Thoracic Oncology, suggest certain proteins correspond to — and may even predict — response to a combined treatment with celecoxib, the generic version of Pfizer’s anti-inflammatory Celebrex, and the epidermal growth factor receptor inhibitor erlotinib, a generic of Genentech’s Tarceva.
“We need good predictors of response to targeted therapy in lung cancer so individual patients receive the specific therapy that targets the particular molecular abnormalities of their tumors,” senior author Steven Dubinett, director of the Jonsson Cancer Center, said in a statement. “This study could determine whether these biomarkers can be used in the future before treatment to select the patients likely to respond.”
The paper was based on a Phase I, dose-escalation, combination drug study of 22 subjects with non-small cell lung cancer receiving celecoxib and erlotinib. All of these advanced lung cancer patients had previously received conventional treatments without success.
About half of the patients had positive outcomes on the therapy — defined as tumors that did not grow or that decreased in size by more than 30 percent. When the researchers used ELISA to analyze patients’ serum protein levels at various time points over two months, they found an intriguing link between treatment response and the levels of four proteins: soluble E-cadherin, a matrix metalloprotein, a tissue inhibitor of MMP, and CCL15.
These proteins apparently act downstream of cyclooxygenase-2, an enzyme causing inflammation that can hinder cancer treatment by vascularizing tumors and making them more resilient. COX-2 — which is overexpressed in 80 percent to 85 percent of lung tumors — also seems to hamper drugs such as Tarceva, which target EGFR on tumor cell surfaces.
Combination therapy with the COX-2 inhibitor Celebrex is intended to restore tumor cell sensitivity and enhance Tarceva’s efficacy, since only 15 percent of patients respond to Tarceva alone.
In this study, the patients who showed positive outcomes after eight weeks also had lower sEC, TIMP-1, and CCL15 serum levels, while patients with low MMP-9 levels before treatment showed the best treatment results. The latter result has researchers optimistic about using MMP-9 as a treatment biomarker for determining the appropriateness of the new combination drug treatment.
Dubinett and his colleagues are currently conducting a larger, Phase II, multi-center study of 100 patients and hope to verify their preliminary connection between tumor size and protein levels during combination drug treatment.