Thank you, Doris , and thank you to the organizing committee to have this opportunity to talk about GOG and NCI resources that are available in the service of translational research in GOG.

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We are about translational research, and that hasn't always been the case in the GOG. We have heard discussions about target identification for therapeutics and biomarkers for prognosis and diagnosis, and molecular targets, genomics, proteomics.

I might highlight some recent papers in the September 1 issue by Birrer and Boyd, and another by Bob Bast, that address a lot of these issues that were discussed early on.

Our interest is in having an impact on prevention, on early detection, prediction of response and resistance to therapy.

Those issues devolve, or have devolved, or maybe evolved, to the committee on experimental medicine.

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Whose goals are to bring strong laboratory-based, hypothesis-driven translational research to the clinical protocols of the GOG.

We have, since 1997, have really been going in this direction to the point where we, I think, are getting very successful in implementing translational research in our trials.

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The aims of the committee on experimental medicine are to generate these novel translational research ideas, to provide a scientific base for consultation to the GOG membership through the development of subcommittees.

This is important. For those of you who don't think about this too often, we do have expertise within the GOG and can identify expertise outside of the GOG in many areas that are highly relevant. For those of you who haven't taken advantage of that, come and see us.

We do approve the scientific content and concept sheets and protocols, as well as approving protocols. We fund seed grants using an NIH-type review, and we, in addition to organizing the annual scientific meetings, we develop and have oversight of CORE labs and the tissue utilization subcommittee.

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Our accomplishments over the past few years have been to bring translational research, as I indicated, to the GOG in a more robust way.

We have developed these funding mechanisms for seed grants as well as translational components in phase I and II studies, and now do a kind of fast track funding of these with high priority studies.

We have modified protocol and concept review procedures, and this has been largely done with the GOG SAT office and largely with Kathleen Darcy, who has made it easier for us to evaluate the protocols and concept sheets, and also I think helps you all in developing your thoughts about how you want to pursue the question you are asking.

As I said, we have subcommittees. We are on the website, and we do the priority reviews. Important, one of our major accomplishments has been to develop core laboratories.

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Which are listed here, and I will just briefly discuss them.

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The molecular pharmacology core lab, originally its aims were to measure expression of drug-resistant associated genes and proteins, primarily in ovarian cancer from patients on protocols, and to correlate this with plasma levels of key drugs from the same patients with the clinical pharmacology core lab.

More recently, there has been a change in emphasis, well, an additional emphasis, to develop novel targets for diagnostics and therapeutics, and a couple of papers have come out of that concept that are listed there.

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The clinical pharmacology core lab, originally headed by Dave Spriggs, is now directed by Marilee Goren at Pitt, with the goal of measuring plasma levels of key drugs from ovarian cancer patients, and to correlate these results not only with the molecular core lab, but with others.

I might point out, apropos of the previous discussion, one of the things that struck me, that can tie a lot of the controversy, the efficacy, the biology that Anil Sood discussed, the biologic agents, especially, and targeting these, nobody has discussed actually delivery of biopharmaceutical agents.

I think this is a major area that needs to be explored, and this involves formulation issues, as well as specific targeting.

There are new techniques available using nanotechnology and genetics to specifically target your payload, if you will, the drug or biologic of interest to the tumor.

That is something that I think one of the core labs is probably going to be involved in heavily in the near future.

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We have more recently added the hormone receptor lab. Kim Lesley directs that, and the aim there is to examine expressions of various estrogen receptors and progesterone receptors.

She is focused right now primarily on endometrial carcinoma, and to relate this to clinical outcomes, but I think ovarian cancer is also available for this.

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One of the most important -- this was discussed throughout the morning -- one of the most important aspects of the GOG is that we have an extraordinary resource in the tumor banks that is supervised by Mike Qualman and Mike Cibull.

These specimens are accessed after review of proposals by the tissue utilization subcommittee, whose members were listed before, Cibull and Boyd.

I would just highlight that the importance of this resource cannot be overemphasized. So, getting to the question about having community docs send your specimens, I think there may be mechanisms through CCOPs to do that. I don't know, but that is something that we can discuss, but this is an incredibly important resource.

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I was also asked to discuss briefly some of the NCI resources that we can also take advantage of. There is the rapid access to intervention development, or RAID.

This is designed to assist translation to the clinic of novel anti-cancer and therapeutic interventions, either synthetic, natural product, or biologics, that we may come about in academia.

The goal is to get a clinical proof of principle that this new molecule or approach is a viable approach for expanded clinical evaluation.

I might point out that, in one of the more recent seed funding initiatives that came out of the committee on experimental medicine, successful competition from Ramki Ramikrishnan at Minnesota, with Linda Carson, with the seed money they got, they were able to generate enough data to then get a RAID grant and take advantage of this resource. I think overall the CEM is doing what it should be doing in terms of fostering translational research.

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There is also, at NCI, the Developmental Therapeutics Program Discovery Services, that has repositories of synthetics and natural products of a lot of things, biologics, and those can be accessed by investigators who want to see if they have got a target that they want to validate.

There is animal production, screening services, which are also important, that may not be readily available to individuals, and there is web-accessible data and tools as well.

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Coupled with this, and with the RAID mechanism, is the Rapid Access to NCI Discovery resources, or RAND, which facilitates research on chemotherapeutic agents in the discovery phase, and assists investigators in discovering small molecules, biologics or natural products through mechanisms like high throughput screening, recombinant target protein product characterization.

Again, once selected, then the RAID mechanism facilitates further preclinical development, and I have told you what the goal of the RAID is.

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Lastly, one of the sponsors of this event here is CTEP, which is within the Division of Cancer Treatment and Diagnosis. CTEP plans and assists and coordinates all aspects of clinical trials, and for that, we appreciate their input.

 

 

So, what is next? Future studies and needs for GOG core resources, and I would put it in the context of where do we want to be in five years? What are the questions that we want to address and focus on in the next five years, and how can the core facilities support the questions of the GOG?

Clearly, the core labs remain available to participate an appropriate high priority focused protocol, working closely with the GOG biostatistics office for development, for example, of novel molecular targets as therapeutic entities, or novel biomarkers as we discussed.

As I said, as I indicated before, I think an important aspect ought to be more pharmaceutical development to enhance efficacy of the agents that we are looking at, especially in preclinical models.

Clearly -- and it has been addressed before -- we need more specimens after relapse or post-therapy. We discussed this at a previous retreat.

It is very difficult to do this, but we have to come up with some way either, if that can't be done in a way that gives us enough specimens, then we have to start thinking more aggressively about biomarkers, as Dr. Bast has been leading us to think about.

Develop unique core resources as a way to foster collaboration. I just am suggesting these, for example, some very high tech proteomics efforts with the four-year transform mass spec and bioinformatics resources and genomics.

I know many of the institutions are doing this, including NCI, and I think there ought to be a way to foster more interactions with the community with those centers that have these resources and, as I said, more integration with NCI resources and SPOREs. With that, my thoughts about where we should go, I thank you for your attention.

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Lastly, one of the sponsors of this event here is CTEP, which is within the Division of Cancer Treatment and Diagnosis. CTEP plans and assists and coordinates all aspects of clinical trials, and for that, we appreciate their input.

 

 

So, what is next? Future studies and needs for GOG core resources, and I would put it in the context of where do we want to be in five years? What are the questions that we want to address and focus on in the next five years, and how can the core facilities support the questions of the GOG?

Clearly, the core labs remain available to participate an appropriate high priority focused protocol, working closely with the GOG biostatistics office for development, for example, of novel molecular targets as therapeutic entities, or novel biomarkers as we discussed.

As I said, as I indicated before, I think an important aspect ought to be more pharmaceutical development to enhance efficacy of the agents that we are looking at, especially in preclinical models.

Clearly -- and it has been addressed before -- we need more specimens after relapse or post-therapy. We discussed this at a previous retreat.

It is very difficult to do this, but we have to come up with some way either, if that can't be done in a way that gives us enough specimens, then we have to start thinking more aggressively about biomarkers, as Dr. Bast has been leading us to think about.

Develop unique core resources as a way to foster collaboration. I just am suggesting these, for example, some very high tech proteomics efforts with the four-year transform mass spec and bioinformatics resources and genomics.

I know many of the institutions are doing this, including NCI, and I think there ought to be a way to foster more interactions with the community with those centers that have these resources and, as I said, more integration with NCI resources and SPOREs. With that, my thoughts about where we should go, I thank you for your attention.

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