If you look at just the last three years, there have been really remarkable advances in diseases that were previously considered completely unresponsive or almost unresponsive to standard therapies. The two most common examples given are in renal cancer and malignant melanoma. Five years ago there was no easily administered therapy for malignant melanoma – in the last year we have two targeted therapies.In an interview with Lauren Smith, the NCI's Dr James H Doroshow talks about the priorities for clinical cancer research and the route to personalised treatment regimes…
Dr James H Doroshow
The National Cancer Institute (NCI) is part of the National Institutes of Health, an agency of the Department of Health and Human Services in the United States. It has primary responsibility for conducting and supporting research, training, health information dissemination, and other programmes in regard to the cause, diagnosis, prevention and treatment of cancer, rehabilitation, and the continuing care of cancer patients.
Dr James H Doroshow, NCI's Deputy Director for Clinical and Translational Research, leads the restructure of the clinical trials process, which has made huge progress since it was given approval from the National Cancer Advisory Board in 2005, and as he explains to Lauren Smith, there have been several key areas of reform.
"Essentially, we have changed the way in which we prioritise the trials that we are going to conduct," he outlines. "Previously, it was carried out through 10 separate groups that were competing with each other to come up with studies to do, which were then reviewed centrally through the National Cancer Institute. Now, we've created a series of disease-oriented scientific steering committees that are populated overwhelmingly by academic investigators with expertise in that particular disease: from a clinical trials perspective and from a translational research perspective, then we also have both academic and private sector positions.
"They get proposals from our standing infrastructure of cooperative groups, which has now been reduced to five, and can also take proposals from investigators anywhere in the United States. The prioritising process is completed based on expert peer review."
The second major change, which is midway to implementation, is a national standard clinical trials data monitoring system, for remote data capture and entry of data from all NCI sponsored trials. Although progress has been complicated, it has now passed a significant milestone with the first trial being incorporated into the software. The system will be used at 3,000 different sites across the US, as well as others in Canada and Europe.
"All NCI sponsored trials will utilise that software, both from the perspective of developing the case report forms and in developing the infrastructure for the particular trial, including those sites that accrue patients but don't develop studies," Doroshow details.
"The biggest advance from our perspective is that on the computer the look and feel of data-entry, irrespective of what kind of study it is in terms of phase or disease, will all look the same. We think that over time this will result in substantially fewer errors and will speed up the process of data entry.
"As it is industry-standard software with all necessary compliance in place, when we do want to collaborate with industry it will be much easier for studies that are going for FDA registration to include the additional data that is required. To the best of my knowledge, there is no comparable system in pharma worldwide."
In addition, there is considerable effort being directed towards enhancing the operational efficiency of the clinical trials network itself. The reconfiguration of 10 groups down to five (one paediatric and four adult) has enabled consolidation of specific areas of expertise and, combined with much more specific and formal guidelines for the timelines of activation of new trials, Doroshow suggests that this reduces by 50 per cent the time it takes to open a new study. Alongside these developments, he is positive about other steps being taken that will, ultimately, result in improved treatment options.
"If you look at just the last three years, there have been really remarkable advances in diseases that were previously considered completely unresponsive or almost unresponsive to standard therapies," he says. "The two most common examples given are in renal cancer and malignant melanoma. Five years ago there was no easily administered therapy for malignant melanoma – in the last year we have two targeted therapies.
"It's very likely that we will continue to find specific ways to target subsets of diseases so that we look at cancer as a collection of many more, smaller numbers of genetically defined diseases. That will be the form that drug development will go forward with and I believe that we are likely to be more successful in that model."
One of the roles of government, Doroshow suggests, is to support innovation in the drug development process, through funding of academic laboratories that are "more likely to take risks that perhaps would not be viewed as appropriate in the commercial sector".
Improving cancer therapeutics at the level of the individual patient and developing personalised medicine has been challenging in the US, he comments, where there have been some barriers to the rapid development of companion diagnostics for specific drugs.
"One of the major tasks that I see the NCI undertaking," he says, " is to facilitate new models for developing the kind of diagnostic tests that will help us to decide specific treatments on a one-on-one patient basis."
Doroshow goes on to highlight further clinical priorities for cancer research: "We're moving towards a circumstance where perhaps if we look 10 years out, all patients will have had their tumours sequenced. We will have a significant amount of genomic and other types of information to help us. I don't think it will be finalised in 10 years, but at that point I expect that the kind of information that we will use to treat patients, especially those in and around clinical trials, will be very different than today."
Beside the development of new drugs, multidisciplinary approaches have been central to cancer treatment for decades, such as combining radiation, surgery and systemic therapies. But there is still more that can be progressed in this way.
"If you take the period beginning in 2000 and consider a 20 year span, we will not only continue to utilise the multidisciplinary clinical talents that are now routinely involved in treating patients with cancer, but those clinical disciplines will now work much more closely with clinical geneticists and biomarker developers," he concludes, "as we move forward to try and tailor our treatments for specific individuals with specific profiles."This article first appeared on publicservice.co.uk: Special Focus: Target, tailor, treat.