Genetics for Next-Generation Cancer Therapies

A new class of genes, called 'cooperation response genes' (CRGs) that can play a role in concocting next generation cancer therapies have been identified by scientists.

The scientists have explained how a large number of genes work in tandem, leading to malignant cell transformation.

They have also indicated the discovery of almost 100 genes that lead to known cancer-causing mutations, and hence provide a number of new opportunities for intervention.

"We believe that we have found a cornerstone for development of new treatments that ultimately will allow selection of drugs and drug combinations from a pool of compounds directed against these new genes. However, much more work needs to be done to explore how our findings may lead to successful targeting of various cancer types and cancer stem cells," Nature quoted lead author Hartmut Land, Ph.D., as saying.

Usually, targeted cancer therapy, such as the drug Gleevec, is based on a keen understanding of cancer mechanism, but despite much research, a clear roadmap leading to dozens of new molecular targets, is still a mystery.

Land has been one of the scientists to discover that malignant cell transformation required multiple mutations in distinct cancer genes and since then, he has been continuing to study the cooperative nature of this process and the inner workings of cancer cell function.

He said that his research team started testing, at the genomic scale, if genes responding synergistically to cooperating oncogenic mutations might act as the "drivers" toward malignancy.

The researchers discovered that out of 30,000 cellular genes, it was only about 100 genes that responded synergistically to the combination of two of the most prevalent cancer genes, Ras and p53, and were expressed differently in normal and cancer cells. Thus, they called these 100 genes as "cooperation response genes" or CRGs.

After studying a subset of the CRGs, it was found that 14 of 24 CRGs played a vital role in tumour formation. On the other hand, just one of 14 genes responding in a non-synergistic manner (non-CRGs) showed a similar effect.

There is a huge significance of Ras and p53, and CRGs, wherein Ras and p53 play a vital role in half of all cancers. When p53, a tumor-suppressor gene, loses its function, and when Ras becomes hyperactive, both these genes aid in promoting uncontrolled growth of colon, pancreas and lung cancers.

Ras activation and p53 loss-of-function works cooperatively work through the CRGs, which encode proteins that regulate cell signaling, cell metabolism, self-renewal, cell differentiation and cell death.

"Indeed, CRGs may provide us with a surprisingly large and valuable set of targets for interventions that will destroy cancer cells and leave normal cells unharmed. We are very excited with the results," said Land.

The study is published in the journal Nature.

Source-ANI
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