Molecular Signature to Predict Response to Cancer Therapy

A molecular signature that that helps account for the aggressive behavior of a variety of cancers may also help identify patients who are likely to respond to a particular anti-cancer drug, according to American scientists.

Researchers at the Moores Cancer Center at the University of California-San Diego (UCSD) say that their findings may lead to a personalized approach to treatment for a variety of solid tumours that are currently resistant to therapies.

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In a study, they have found that a receptor sitting on the surface of certain aggressive tumour cells can activate a key enzyme, src-kinase, which helps tumour cells to become more aggressive in the body.

Writing in their study report, the researchers have pointed out that this enzyme is the target of the anticancer drug dasatinib, which blocks its activity and is currently approved for treating chronic myelogenous leukemia (CML).

They further state that the scientists the presence of the receptor - a protein called integrin alpha-v beta-3 - on some of the more common solid tumors such as breast, colon, lung and pancreas could help identify individuals with many other types of cancer that are also likely to respond to the drug.

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"These results could enable us to identify the subpopulation of cancer patients who are likely to respond to treatment with dasatinib," Nature magazine quoted Dr. David Cheresh, professor and vice chair of pathology at the UC San Diego School of Medicine and the Moores UCSD Cancer Center, who led the work, as saying.

"Rather than treat all patients with a given tumor type the same way, by identifying a specific molecular signature consisting of the receptor and its activated enzyme, we can customize the treatment in such a way that we impact the patients most likely to be sensitive to a drug," he added.

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During the study, the researchers compared the growth properties of pancreatic and breast cancer cells that expressed the alpha-v beta-3 receptor with those that did not.

Their effort led to the discovery of a molecular pathway that accounted for the increased malignancy.

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"Once we identified the pathway, we immediately realized that the drug dasatinib, which targets this pathway, would be a logical choice to use against these cancers," Cheresh said.

Experimenting on a pre-clinical model of pancreatic cancer, the researchers have confirmed that tumour cells with the receptor responded to the drug, while those not expressing receptors did not.

Cheresh pointed to pancreatic cancer tumours, approximately 60 percent of which carry the marker on the tumour cell surface.

"We would argue that pancreatic cancer patients with alpha-v beta-3 would respond to dasatinib," he said.

According to him, tumours that lack the marker appear to be resistant to the drug.

"We discovered an unexpected pathway that accounts for increased malignancy in a population of some of the most dangerous cancers," he said, noting that the marker could be identified by a biopsy.

"There are features of the findings that allow us to implicate dasatinib not just for a single tumour type, but for all tumours with the malignant signature," he added.

Dr. Barbara Parker, medical director of oncology services at the Moores UCSD Cancer Center, said: "These observations suggest a strategy for testing the effectiveness of dasatinib in breast cancer patients who are positive for the alpha-v beta-3 receptor."

A research article on the study has been published in the online edition of the journal Nature Medicine.

Source-ANI
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