NextBio predicts mechanisms underlying drug toxicity and identifies new cancer biomarker

Oct 15 2011

New research presented this week highlights the ability of NextBio to help life scientists and clinicians investigate publicly available genomic data to assess biological mechanisms underlying drug toxicity, as well as discover prospective cancer biomarkers for further validation. The unique capabilities of NextBio to search and make discoveries, not possible by other methods, from the massive amounts of genomic data increasingly available in the public domain is the subject of two poster presentations at the American Society of Human Genetics/International Congress of Human Genetics meeting in Montreal, October 11-15.

In one presentation, the authors showed how NextBio's web-based tools and integrative genomics data could be used to evaluate potential drug toxicities and suggest treatment alternatives for women experiencing "hot flashes" (vasomotor symptoms) as a result of breast cancer chemotherapy. In another presentation, NextBio authors demonstrated how genomic data from disparate sources could be brought together and analyzed on the NextBio platform to suggest a potential new cancer biomarker in a region of the genome previously termed a "gene desert."

Drug Toxicity, Alternative Therapy Identified by NextBio

NextBio analysis offers the potential to inform clinical medicine through its ability to predict drug toxicities, as illustrated by a study of tibolone, a drug widely used to treat menopausal vasomotor symptoms. In 2009, a clinical trial tested this drug as a potential therapy for similar symptoms in women undergoing breast cancer treatment. The trial was cut short early because of the significant increase in cancer recurrence observed in those women.

The authors' investigation of public genomic data curated by NextBio found positive correlations between tibolone-induced gene expression changes and those seen in breast cancer, as well as similarities to the gene expression profiles of estradiol hormone replacement therapy (HRT), which is contraindicated in patients with breast cancer. A similar analysis for gabapentin, another drug used to treat vasomotor symptoms, showed gene expression changes that are not correlated with breast cancer, HRT, or tibolone signatures, suggesting that gabapentin may offer a better alternative to tibolone for patients with breast cancer.

"Together, these and other analyses performed as part of this study demonstrate that NextBio's web-based tools and integrative genomics data can aid applications such as assessment of potential drug efficacy or adverse effects," said Helen Wang, NextBio scientist and lead author of the study.

Identification of Potential New Cancer Biomarker

A second study presented by NextBio showed how using genomic data curated from publicly available sources; researchers could perform in silico analysis to identify a possible new cancer biomarker in a portion of the genome previously known as a "gene desert".

Cellular changes involved in cancer are not unlike those involved in creating stem cells from adult tissues like skin. In both cases, cells re-gain the ability to multiply rapidly, and lose certain characteristics of adult, differentiated tissues. Analyzing data integrated from studies of genomic changes in stem cells with studies of several cancer types, the group identified a poorly characterized gene that was highly up-regulated in both cancer cells and stem cells, but not normal mature or otherwise differentiated cells.

"NextBio offers an unprecedented opportunity for life scientists to find correlations and make new findings from the rapidly rising mountains of publicly available genomic data, as well as from their own research results," said Ilya Kupershmidt, NextBio vice president of products. "As we enter the era of the $1000 genome, the NextBio platform can provide an important resource for analyzing and understanding genomic data from disparate sources, leading to new knowledge and the potential for better decision making for life science researchers, drug developers, and clinicians alike."