Genetic variations ensure that no two people—or their cancers—are alike. Tools and knowledge help researchers predict how individuals will respond to cancer therapy, enabling more precise and effective treatment.
At the 2008 Annual Meeting of the American Association for Cancer Research (AACR) researchers presented data on new biomarkers that can predict response to treatments.
Kidney and Non-small Cell Lung Cancer
Researchers have identified two potential biomarkers that could help doctors monitor the effectiveness of treatment with sunitinib or bevacizumab for kidney and non-small cell lung cancer.
“Our work provides novel data on a potential biomarker for the monitoring of anti-angiogenic drug activity in cancer patients, as well as identifies a cell type that is a potential target for these agents,” said Laura Vroling, M.Sc., a researcher in the Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
The vascular endothelial growth factor (VEGF) receptor targeted agents bevacizumab and sunitinib have proven effective against several cancers, such as non-small cell lung cancer, colorectal and kidney cancer, but it is unclear which subset of patients will benefit most from these agents, researchers say. “Therefore, it is of great importance to identify and validate biomarkers for early response or duration of response,” Vroling said.
Abstract 4956: CD34bright/CD133neg candidate circulating Endothelial Progenitor Cells (ccEPCs) are a potential biomarker during treatment with sunitinib or bevacizumab
Breast Cancer
Dutch researchers report identifying a set of seven genes responsible for drug resistance and aggressiveness in the most common form of breast cancer. These genes, some of which are novel, could provide therapeutic targets for personalized treatment of breast cancer and, possibly, for prevention of disease, they say.
These genes are found in estrogen receptor-positive (ER+) breast cancer, which investigators say is usually more treatable than breast cancer that is not fueled by estrogen. The majority of human breast tumors are ER+ and most respond to anti-estrogen therapy, such as tamoxifen. But in advanced disease, only half of ER+ breast cancer is initially sensitive to tamoxifen, and in the majority of those patients, the disease eventually becomes resistant to drug therapy. Understanding the molecular basis of this drug resistance was the focus of the Dutch study.
A research team from Erasmus Medical Center in Rotterdam hypothesized that cell proliferation in the absence of estrogen and in the presence of tamoxifen would be regulated at a molecular level by specific genes. To identify these genes involved in cell growth, they used a functional screen based on insertion mutagenesis with mouse retroviruses. This unique approach in human solid tumor cells took more than a decade of painstaking work.
Some of the seven genes the researchers found – which they have included in a new family dubbed “Breast Cancer Anti-estrogen Resistance” (BCAR) – are already associated with cancer development in general but others are novel. Few of the seven (AKT1, AKT2, BCAR1, BCAR3, EGFR, GRB7, and TRERF1) had been linked to resistance to tamoxifen.
Abstract 1582: Identification of BCAR genes relevant for breast cancer progression and endocrine therapy resistance
Breast Cancer
A HER2 peptide E75 vaccine reduced mortality in patients with HER2-positive breast cancer by half, according to Texas researchers.
In particular, patients with low-expressing HER2 tumors exhibited better response, not only immunologically, but clinically, with decreased breast cancer recurrence and no mortality following vaccination, report researchers from Brooke Army Medical Center in San Antonio, Texas.
“The fact that HER2 low-expressors responded so favorably not only underscores the difference in mechanism between the vaccine vs. antibody therapy like trastuzumab, but also offers the hope of additional adjuvant therapy to the largest subset of breast cancer patients if proven in the upcoming phase III trial,” said Linda C. Benavides, M.D., a resident in general surgery at Brooke Army Medical Center.
Abstract 2545: Response to preventive HER2/neu peptide (E75) vaccine based on HER2/neu status
Pediatric Neuroblastoma
Australian researchers have identified a potential new target for treatment of neuroblastoma, the most common solid tumor among young children.
The treatment involves inhibiting the production of ornithine decarboxylase (ODC1), a gene driven by the MYCN oncogene that is a powerful predictor of death from this disease. Researchers report that ODC1 inhibition delayed or prevented the development of neuroblastoma in a clinically relevant animal model, suggesting that suppressing ODC1 could be target for treating this cancer.
“This disease, particularly in patients whose tumors carry multiple copies of the MYCN oncogene, has a particularly poor prognosis and new therapies are urgently needed,” said Michelle Haber, Ph.D., professor and executive director of Children’s Cancer Institute Australia for Medical Research in Sydney, Australia. “Our findings suggest that MYCN-driven over-expression of ODC1 in this disease, or genetic variations associated with increased expression of the gene, contribute to the aggressive biology of this tumor, and that inhibition of this gene may lead to an important new therapeutic avenue for this disease.”
Abstract 5832: Overexpression of ODC1 is associated with poor outcome in childhood neuroblastoma and represents an important therapeutic target
Filed Under: Drug Discovery
