Preclinical trials show ALK1 inhibitor dalantercept may prevent metastasis

Kristian Pietras

Dalantercept (ACE-041) is owned by Acceleron ($XLRN) and is currently in early clinical trials for liver and kidney carcinomas. More recently, though, researchers at Lund University demonstrated that it could block the activin receptor-like 1 (ALK1) pathway, suggesting it may also slow metastasis in aggressive breast cancer.

Kristian Pietras and colleagues showed in a range of mouse models of breast cancer that by inhibiting ALK1 with dalantercept, they could effectively block metastatic dissemination--and more specifically the spread of the primary tumor to the lungs. They published their preclinical work on Monday in Cancer Research, a journal of the American Association for Cancer Research,

The ALK1 protein plays a key role in metastasis, according to the researchers, allowing tumor cells to gain access to blood vessels, which in turn assist in metastasis.

They concluded that in a gene-expression panel from samples of 768 breast cancer patients there was a correlation between high levels of ALK1 in their tumors' vasculature and the likelihood of developing metastatic cancer. Cross-referencing ALK1 expression with The Cancer Genome Atlas database supported their discovery.

"We have studied ALK1 for a long time and realized that the protein is central to the new formation of blood vessels in tumours," says the scientist. "By investigating almost 2000 breast tumours, we found in the present study that patients with high levels of ALK1 in the tumour blood vessels were much more likely to develop metastases. Women with a low level of the protein consequently had fewer relapses and thereby survived longer."

Pietras highlighted the need for new therapies in metastatic cancers. "Although prognosis is relatively good when detected in its early stages, metastatic disease is the cause of 90% of all cancer-related deaths," he noted in a statement. "Therefore, learning more about the metastatic process and finding new cures to inhibit the advancement of metastatic disease is a clinical priority."

Currently, they're continuing their preclinical work on the precise therapeutic regimen and disease stage at which the treatment using dalantercept is most effective before moving forward with clinical trials.

- here's the release
- get the research abstract

Sponsored By Metabolon

Five Translational Insights Key to a Successful First-in-Human (FIH) Study – Metabolite-Based Biomarker Discovery and Validation

Translational success rates from pre-clinical animal studies to human clinical trials remain frustratingly low. Learn how metabolomics helps you bridge between the theoretical & practical, between the function & actual activity of your drug molecule to get you closer to the phenotype, sooner.