Currently genetic information is considered personal, with the emphasis on respect for patient confidentiality. But patients often only seek genetic testing because of their family history, so results could more appropriately be viewed as necessary information for treating the whole family, write the authors.
The current "personal account model" emphasises patient centredness in medicine. Under this model, an individual patient's information is kept confidential unless there is a strong reason for it to be disclosed, eg serious harm to a relative.
However, this approach means that relatives can miss out on important information and health care, say the authors. Instead genetics could adopt a "joint account model", which classes genetic information as familial rather than personal, and makes it available for the treatment of other family members except where there are good reasons not to do so.
Which of these models should apply in practice? The personal model is consistent with good practice in other areas of medicine, say the authors. Nevertheless, the familial nature of genetics means that under this approach, relatives may not receive appropriate healthcare due to lack of information. In the interests of justice, they argue, sharing genetic information should become routine, except in special circumstances.
Changing to a joint model is controversial, but where there is no risk of serious harm to patients or their relatives, it would extend the benefits of testing to the whole family, they conclude.
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Kuriyan's work caught the attention of Sawyers, who was examining how mutations in the ABL kinase could blunt the effect of Gleevec. Sawyers and Kuriyan began a collaboration to probe the problem, which culminated in a publication in the August 2002 issue of the journal Cancer Cell, reporting the identification of 15 mutations in the BCR-ABL gene that caused resistance to Gleevec.
In that paper, Kuriyan's structural studies revealed that only a subset of patients bore a mutation right at the point where Gleevec would bind to BCR-ABL to inhibit it. Instead, most patients had mutations that impaired the flexibility of the kinase, preventing it from assuming the off position. To Sawyers and others, this raised the possibility that a second drug ” a sloppier inhibitor than Gleevec that didn't hold the target to such tight structural constraints ” might work against the mutations. In short, Sawyers wondered whether a drug that bound Abl in the on position, like a Src inhibitor, would be the model for Gleevec's second coming.
Over time, Sawyers's musings became more public. I was giving scientific talks on the structural implications of Gleevec mutations and stating that I thought that a Src inhibitor would be a good idea, said Sawyers. This was an informed guess based on what we were seeing in the crystallography data.
As fate would have it, Bristol-Myers Squibb had a dual Abl/Src inhibitor under development. Sawyers received a phone call from Bristol-Myers Squibb - and BMS-354825's reincarnation as a cancer drug was under way.
As Sawyers is quick to point out, only time - and further research - will tell whether the drug makes it into the clinic. Early signs are good. This could be the first drug to get around kinase resistance, and that has broad implications, Sawyers said. If this drug should prove to be safe and effective in the clinic, one can envision using this in a combination kinase inhibitor therapy for CML.
BMS-354825 is currently being evaluated at UCLA and MD Anderson Cancer Center in Houston in phase I clinical trials in CML patients with Gleevec resistance.
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