Spanish gene expression data promise targeting of anti-angiogenesis treatment

Analyzing the expression of particular genes in lung cancers could soon allow researchers to identify groups of patients who are likely to benefit most from treatment with angiogenesis-inhibitor drugs, a Spanish team reports.

Dr Eloisa Jantus from the General University Hospital of Valencia reports new findings from an analysis of 135 lung cancer specimens. She and her colleagues, led by Dr Carlos Camps, evaluated the expression of 8 different genes related to vascular endothelial growth factor (VEGF), a molecule that helps tumors develop the blood supply they need to grow larger. VEGF is a key target for new "anti-angiogenesis" drugs that aim to arrest this process.

"The vascular endothelial growth factor (VEGF) family of ligands and receptors has an important role in tumor angiogenesis," Dr Jantus said. "We studied the expression, at molecular level, of the members of this family in tumor samples as well as in normal lung tissues in order to understand their role in tumor development and prognosis."

The group measured the expression of the 8 genes, including VEGF A, -B, -C and PIGF, tyrosine-kinase receptors VEGFR-1, VEGFR-2 and VEGFR-3. In addition to these receptors, they also studied related genes for neuropilins NRP1 and NRP2.

The researchers then correlated gene expression levels with important clinical outcomes, including overall survival and the time to tumor progression, in patients whose tumors were surgically removed.

"Patients whose tumors expressed high levels of VEGF-A and VEGFR-1 tended to have a worse prognosis in terms of progression-free survival and overall survival," Dr Jantus said. "The subgroup of patients with high levels of expression of VEGF-A and VEGFR-1 showed a 30% shorter time to progression and overall survival, when compared to those with low expression levels."

The findings provide early clues that 'angiogenic profiles' could define subgroups of patients who will better benefit from the use of anti-angiogenic therapies, the researchers say.

"We think that it seems improbable that a single angiogenic marker will provide all of the relevant clinical information because only one biomarker cannot reflect the complexity of the angiogenic process; however, when the markers were considered in combination, they provided a more comprehensive pattern or profile, significantly improving their prognostic value."

These angiogenic profiles need validation in larger groups of patients before they can be implemented in the clinic, the researchers note, however they represent an emerging way to improve lung cancer therapy by tailoring it to the characteristics of individual patients and their tumors.