Radiolabeled hedgehog can differentiate stem-like cancer cells, identify aggressive tumors

January 12, 2016

"The field is still emerging because while circulating tumor cells have been studied in patients with metastatic cancer, the idea of localized cancer is still new," said Nagrath. "We haven't had the right tools before; with the CTC-chip we potentially have the necessary tool."

LB-174. Use of massively parallel, next-generation sequencing to identify gene mutations beyond KRAS that predict response to panitumumab in a randomized, Phase III, monotherapy study of metastatic colorectal cancer (mCRC)Using next-generation sequencing technology, researchers have identified multiple gene mutations that may alter a patient's response to panitumumab for metastatic colorectal cancer.

"One of the pressing goals is to identify predictive biomarkers for drugs such as panitumumab. This technique provides a method to simultaneously evaluate multiple genes within a tumor," said David M. Reese, M.D., executive medical director in medical sciences and head of the oncology early development group at Amgen, Thousand Oaks, Calif.

Reese and colleagues used the Roche 454 pyrosequencing technology to investigate whether mutation of genes, beyond the KRAS gene mutation, altered colorectal cancer response to panitumumab. KRAS gene mutation is an established biomarker for a lack of response to anti-epidermal growth factor receptor antibodies. Using tumor samples from 288 patients with metastatic colon cancer, they investigated mutations in nine genes: KRAS (exon 3), BRAF, NRAS, AKT1, CTNNB1, EGFR, PIK3CA, PTEN and TP53.

On average, eight genes were evaluable per patient. More than one mutation was found in 109 tumors and 20 tumors had more than one mutation in a single gene. Two tumor samples yielded KRAS and BRAF mutations, suggesting that the presence of these mutations together is not always mutually exclusive, which has been previously reported, according to Reese.

Further, this study confirmed that simultaneously testing multiple biomarkers in one tumor sample is possible.

"The ability of this sequencing technology to assess multiple genes in parallel may permit the more rapid development of truly personalized medicine," said Reese.

There is still much work to be done though, according to the researchers. Two large Phase III trials have been completed and the next step is to see if the predicative ability of these genetic profiles is influenced when patients undergo combination chemotherapy.

4335. Imaging of cancer stem cells with radiolabeled Hedgehog

A new imaging agent ?? radiolabeled hedgehog ?? detects cancer stem cells, potentially allowing for imaging of "stem cell-like" cancer cells by positron emission tomography (PET) in patients with breast cancer, according to results of a pilot study.

Cancer stem cells are resistant to chemotherapy and radiotherapy and can lead to tumor regrowth after treatment. Tumors that are rich in stem cell-like cancer cells are more likely to recur after treatment and to metastasize. Detecting these cells early means timely initiation of aggressive treatments to minimize relapse and improve therapeutic outcome. It may also be useful in evaluating new stem-cell targeted cancer therapies.

Jennifer Sims-Mourtada, Ph.D., director of molecular research and development at RadioMedix, Inc., Houston, Texas, and colleagues tested the ability to detect breast cancer stem cell-like populations using a protein, sonic hedgehog that was radiolabeled with the positron emitting isotope Gallium-68.

Increased activation of the hedgehog pathway is observed in cancer stem cells and aggressive tumors.

Binding of the radiolabeled hedgehog to the Patched-1 hedgehog receptor on the surface of breast cancer cells occurred, suggesting potential for molecular imaging of breast cancer by PET. A significant increase in binding was observed in cultures enriched for breast cancer stem-like cells.

"Our study is the first to show that radiolabeled hedgehog is capable of differentiating stem-like cancer cells compared to the entire tumor population," she said. "Additionally, this agent can potentially identify aggressive tumors."

These results are being validated in further laboratory work and microPET imaging studies are underway to assess the value of this agent for imaging tumors that are rich in cancer stem cell populations, according to Sims-Mourtada.

SOURCE American Association for Cancer Research