Potential Biomarkers for Breast and Head-and-Neck Tumors Presented at Cancer Conference
Growth-factor proteins predict risk and identify patients with disease (Oct. 11)
Acceleron Pharma, Inc., a biopharmaceutical company based in Cambridge, Mass. announced on October 11 that it is presenting data at the 2012 Markers in Cancer Conference in Hollywood, Fla., that illustrate possible new biomarkers for use in metastatic breast cancer and in squamous-cell carcinoma of the head and neck.
The two poster presentations describe the potential role of activin A as an adverse biomarker for patients with metastatic breast cancer and of bone morphogenic protein 9 (BMP9) as a biomarker for the identification and selection of patients with head-and-neck cancer.
Acceleron’s research efforts are focused on developing medicines that regulate members of the transforming growth factor (TGF)-beta superfamily of proteins, which includes activin A and BMP9. These proteins have fundamental roles in regulating the growth and differentiation of various cell types and are involved in cancer.
About half of patients with HER2-positive metastatic breast cancer will respond to first-line trastuzumab (Herceptin)-containing therapy, but most will progress within 1 year. Resistance to trastuzumab remains a clinical problem, and better predictive and prognostic biomarkers are needed, the company says.
Serum activin A was measured in 60 patients with metastatic breast cancer before starting first-line trastuzumab-containing therapy. Progression-free survival (PFS) and overall survival (OS) were analyzed. Higher serum activin A was significant on a continuous basis for predicting reduced PFS to first-line trastuzumab-containing therapy (P < 0.003) and for predicting shorter OS (P < 0.0001).
When analyzed using a dichotomous (median) cutpoint, the cohort with elevated serum activin A had a significantly reduced median PFS versus the cohort without elevated activin A (6.6 months vs. 31.1 months, respectively; P < 0. 002) as well as significantly reduced median OS (19.6 months vs. median not reached, respectively; P < 0.0001). In a multivariate analysis for PFS with other covariates (age, line of therapy, carcinoma antigen 15-3 [CA 15-3], and hormone receptor status), activin A was the only significant covariate (P = 0.021). In a multivariate analysis for OS, activin A (P = 0.002) and CA 15-3 (P = 0.03) remained significant as prognostic factors.
The National Cancer Institute estimates that more than 47,000 patients will be diagnosed with squamous-cell carcinoma of the head and neck in the U.S. in 2012. Head-and-neck cancer remains a clinically challenging disease, and with only one new drug therapy approved in the past 50 years, the prognosis for patients with recurrent or metastatic disease remains poor.
Researchers found elevated expression of BMP9 in tumor samples from patients with squamous-cell carcinoma of the head and neck. The data suggest that BMP9 has a potential role as a biomarker for selecting patients who might benefit from treatment with the investigational drug dalantercept — Acceleron’s phase II activin receptor-like kinase 1 (ALK1) inhibitor, formerly known as ACE-041.
BMP9 is a ligand that binds with high affinity to ALK1 and regulates the maturation stage of angiogenesis. In an analysis of archived tumor samples from patients with squamous-cell carcinoma of the head and neck, 79% of the samples had either medium or high expression of BMP9.
Dalantercept is an ALK1 receptor fusion protein that binds to BMP9 and BMP10 and inhibits their signaling through the ALK1 receptor.
Dalantercept is currently in a phase II clinical trial for the treatment of patients with squamous-cell head-and-neck cancer.
For more information, visit the Acceleron Pharma Web site.