In challenge to personalized cancer care, DNA isn’t all-powerful | Reuters

A DNA double helix in an undated artist's illustration released by the National Human Genome Research Institute to ReutersA good note of caution on some of the promises of genetic-based personalized medicine, and a reminder of the complexity of cancer and the human body. Quote:

If DNA is not the sole driver of tumors’ behavior, said molecular geneticist John Dick of the Princess Margaret Cancer Centre in Toronto, who led the study, it suggests that, to vanquish a cancer entirely, drugs will have to target their non-genetic traits too, something few drug-discovery teams are doing…..

“I thought we’d be able to look at the genetics that let some cells propagate, or not be susceptible to chemotherapy, but lo and behold there was no genetic difference,” said Dick. “That goes against a main dogma of the cancer enterprise: that if a tumor comes back after treatment it’s because some cells acquired mutations that made them resistant.”

That’s true in some cases, he said, “but what our data are saying is, there are other biological properties that matter. Gene sequencing of tumors is definitely not the whole story when it comes to identifying which therapies will work.” ….

Other experts also praised the work, saying it supported the growing suspicion in the field that personalized cancer therapy is oversimplistic, at least in how it’s sold to the public.

“It’s not as simple as just sequencing mutations to tailor therapies to each tumor,” said surgical oncologist Dr. Steven Libutti of the Montefiore Einstein Center for Cancer Care in New York City. “In my mind, the findings are not unexpected. Other things besides genes matter: the environment in which a tumor is growing, for instance, plays an important role in whether therapy will be effective.”

Rather than targeting DNA alone, the Toronto scientists suspect, effective therapies would also take aim at what phase of its cycle a cell is in (dormant, growing or dividing, for example), which of its genes are activated, whether it sits in a region of the tumor that is starved of oxygen, and other non-genetic properties.

Nudging tumor cells out of their dormant phase and into their growth cycles, for instance, could make them more susceptible to chemotherapy, which generally targets rapidly dividing cells.

“Our findings raise questions about the resources put into sequence, sequence, sequence,” said Dick. “That has led to one kind of therapeutic” – molecularly-targeted drugs – “but not the cures the public is being promised.”

In challenge to personalized cancer care, DNA isn’t all-powerful | Reuters.


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