The focus of the 22nd Annual Detroit Cancer Symposium was the presentation and discussion of cytotoxic agents, with a significant portion of the symposium including the exciting frontiers of drug discovery being explored by the National Cooperative Drug Discovery Groups (NCDDG) Program. The symposium brought together a large number of investigators from government, universities and pharmaceutical companies involved in the discovery and development of new anticancer agents. Exciting new leads were presented and the status of others presently under development was discussed. Of particular significance has been the initiation of renewed efforts in the area of natural product drug discovery, where the discovery of new cytotoxics is very promising at the moment. A number of major changes have occurred during the last decade in research on drug discovery of cytotoxic agents. Critical reviews of a number of the models and concepts underlying drug discovery represented a continuous thread throughout the meeting, being constantly discussed in terms of their advantages, disadvantages and capabilities of discovering solid tumor active anticancer agents. A recent development which is to be much applauded and which portends to great discoveries is the new relationship formed between Government, University of Industry. The NCDDG mechanism which stimulates this interaction is an inexpensive manner to greatly magnify the drug discovery and development effort nationally. Cytotoxic Anticancer Drugs: Models and Concepts for Drug Discovery and Development represents a forum which will become the major mode for bringing together these three different components in the equation to regularly discuss new results and ideas.

With the publication of these proceedings from the Second Drug Discovery and Development Symposium, this forum has become the main mechanism for bringing together the principal groups involved in both discovering and developing new approaches to the treatment of cancer. This Second Symposium emphasized the types of materials being discovered and their therapeutic activity. This is especially evident in the natural product discovery programs, where unique and active structures are being identified. The major contributors to the meeting were the investigators participating in the National Cooperative (Natural Products) Drug Discovery Groups [NC(NP)DDG]. These groups reflect an association among researchers at universities or cancer centers, pharmaceutical companies and the National Cancer Institute. Their sources of materials are varied, reflecting chemical inventories of pharmaceutical companies, organic synthetic compounds from the laboratory, cytotoxics as well as biologics and their hybrids, and natural products obtained from plants, marine organisms and microorganisms. The models employed in the discovery systems vary from broadly cellular based to specific enzymes to defined cellular functions. Each of them is believed important to the malignant state and will allow for the discovery of compounds which will have efficacy in cancer therapy. The goal of the participants is both to discover new anticancer agents and to develop them as efficiently as possible into clinically useful additions to treatment. Of importance is the fact that there are a number of promising leads which will soon be moving into the clinic thereby testing the effectiveness of this NC (NP) DDG approach.

This year notes two major changes in the annual Detroit Cancer Symposium. The first is our intention of selecting top ics of broad interest to the cancer community and examining the subject from both a basic laboratory and clinical viewpoint. In this way, the importance of both elements of cancer research are noted and the interplay between them emphasized. Further, we believe that Symposia such as this act to stimulate the basic scientist and clinician to continue their studies with the know ledge of the impact that each has upon the other and the nec essary cooperation required to solve the cancer problem. The second change is the publication of this Symposium. The pre vious sixteen were not committed to manuscript form. Given the change in format and intent of the series, we believe that this and subsequent volumes will make important contributions to the cancer literature. The topic of "Biology and Therapy of Acute Leukemia" was chosen for the first Symposium because of its historical signif icance in cancer chemotherapy. The therapeutic rationale for human leukemia is the result of understanding the basic tumor biology largely derived from transplantable leukemias in exper imental animals. It is through these models, as discussed by Dr. Fred Valeriote, that we learned the cellular kinetics of leukemia, the antileukemic effects of new agents and the ef fect of growth perturbation by various chemotherapeutic agents and their combinations.

Biochemical Modulation at the present time defines an area of study in which the intracellular metabolism of a given anti cancer agent is modulated (usually by a noncytotoxic agent or a cytotoxic agent at sufficiently low dosage to make it non cytotoxic) in order to either increase the effectiveness of the particular agent against tumor cells or decrease its cytotox icity against normal cells. The major focus of modulation has been the agents 5-fluorouracil (FUra), arabinofuranosylcytosine (ara-C), methotrexate (MTX) and a few alkylating agents. The major thrust of the studies has been to increase the flow of the anticancer agent along the pathway responsible for the formation of the cytotoxic species: for example, FUra to FUTP or ara-C to ara-CTP. While in most cases the application of research re sults to clinical trials does not require the subsequent exper tise of the laboratory researchers, application of biochemical modulatory schemes to clinical protocols necessitate a dramatic break with the past procedures. As shown in the laboratory clinical loop below, close collaboration between the laboratory and clinical investigator is essential. While the laboratory REDEFINE TECHNOLOGY, TESTS OR QUESTIONS FOR FURTHER THERAPEUTIC ADVANCE CLINICAL EXPERIMENTAL PROTOCOL (LABORATORY) RESEARCH STUDIES DEFINE AND TEST APPROPRIATE SCIENTIFIC PARAMETERS results define rationally-based regimens, it is essential that the clinical protocols contain the requirement that clinical material (either tumor or normal tissues) be sampled to deter mine whether the biochemical modulation being proposed is in fact beinq accomplished.

Over the past decade, techniques have been developed and implemented to observe metabolism noninvasively in localized regions of intact, living experimental animals and humans through the use of magnetic resonance spectroscopy (MRS). At the same time, magnetic resonance imaging (MRI) techniques developed in the 1970s and refined in this decade have been increasingly applied as a powerful clinical tool to probe human anatomy. Because of the unusual metabolic and physiologic characteristics of malignant tissues, oncology has been one of the primary focuses of the application of both MRS and MRI. Although considerable progress has been made in oncologic applications of magnetic resonance (MR), further research is needed to realize the full potential of MR in this area. Consequently, the 21st Annual Detroit Cancer Symposium entitled "Magnetic Resonance in Experimental and Clin ical Oncology" was organized to provide a forum for researchers in the field to report the state of the art of MRS and MRI in oncol ogy, to discuss future goals for MRS and MRI in oncology, and to define the research needed to meet those goals. The major emphasis of the symposium was on MRS due to both the recent widespread availability of clinical MRS instrumentation and the extensive amount of animal MRS research performed over the past half decade.

The focus of this symposium was on the present and future capabilities of flow cytometry for both medical and biological applications in cancer. This technology began with quite modest instrumentation, with limited capabilities to answer biological questions. Today, both the clinical workhorses and the powerful multi-laser, multi-detector, sorting machinery, coupled with sophisticated computers and storage devices and the increasing storehouse of markers and dyes, are taking us to the limit and beyond in finding answers to the cause and cure of cancer. In the past, both normal hematopoietic tissue and leukemias have been the tissue samples of choice in the application of flow cytometry, and some of the most recent applications with these tissues are presented here. However, the book also discusses the increasingly sophisticated disaggregation techniques which allow investigators the possibility to train their lasers on solid tumors. Not only can we use flow cytometry with associated fluorescent markers to understand the biology of cancer, but also the wide array of existing and developing markers provides us with important diagnostic tools in the detection of cancer early in either the malignant or relapse process. And the field comes full circle, with the use of the technology for gene mapping and other genetic studies to unlock the basic malignant process.

The focus of this symposium was on the present and future capabilities of flow cytometry for both medical and biological applications in cancer. This technology began with quite modest instrumentation, with limited capabilities to answer biological questions. Today, both the clinical workhorses and the powerful multi-laser, multi-detector, sorting machinery, coupled with sophisticated computers and storage devices and the increasing storehouse of markers and dyes, are taking us to the limit and beyond in finding answers to the cause and cure of cancer. In the past, both normal hematopoietic tissue and leukemias have been the tissue samples of choice in the application of flow cytometry, and some of the most recent applications with these tissues are presented here. However, the book also discusses the increasingly sophisticated disaggregation techniques which allow investigators the possibility to train their lasers on solid tumors. Not only can we use flow cytometry with associated fluorescent markers to understand the biology of cancer, but also the wide array of existing and developing markers provides us with important diagnostic tools in the detection of cancer early in either the malignant or relapse process. And the field comes full circle, with the use of the technology for gene mapping and other genetic studies to unlock the basic malignant process.

With the publication of these proceedings from the Second Drug Discovery and Development Symposium, this forum has become the main mechanism for bringing together the principal groups involved in both discovering and developing new approaches to the treatment of cancer. This Second Symposium emphasized the types of materials being discovered and their therapeutic activity. This is especially evident in the natural product discovery programs, where unique and active structures are being identified. The major contributors to the meeting were the investigators participating in the National Cooperative (Natural Products) Drug Discovery Groups [NC(NP)DDG]. These groups reflect an association among researchers at universities or cancer centers, pharmaceutical companies and the National Cancer Institute. Their sources of materials are varied, reflecting chemical inventories of pharmaceutical companies, organic synthetic compounds from the laboratory, cytotoxics as well as biologics and their hybrids, and natural products obtained from plants, marine organisms and microorganisms. The models employed in the discovery systems vary from broadly cellular based to specific enzymes to defined cellular functions. Each of them is believed important to the malignant state and will allow for the discovery of compounds which will have efficacy in cancer therapy. The goal of the participants is both to discover new anticancer agents and to develop them as efficiently as possible into clinically useful additions to treatment. Of importance is the fact that there are a number of promising leads which will soon be moving into the clinic thereby testing the effectiveness of this NC (NP) DDG approach.

The focus of the 22nd Annual Detroit Cancer Symposium was the presentation and discussion of cytotoxic agents, with a significant portion of the symposium including the exciting frontiers of drug discovery being explored by the National Cooperative Drug Discovery Groups (NCDDG) Program. The symposium brought together a large number of investigators from government, universities and pharmaceutical companies involved in the discovery and development of new anticancer agents. Exciting new leads were presented and the status of others presently under development was discussed. Of particular significance has been the initiation of renewed efforts in the area of natural product drug discovery, where the discovery of new cytotoxics is very promising at the moment. A number of major changes have occurred during the last decade in research on drug discovery of cytotoxic agents. Critical reviews of a number of the models and concepts underlying drug discovery represented a continuous thread throughout the meeting, being constantly discussed in terms of their advantages, disadvantages and capabilities of discovering solid tumor active anticancer agents. A recent development which is to be much applauded and which portends to great discoveries is the new relationship formed between Government, University of Industry. The NCDDG mechanism which stimulates this interaction is an inexpensive manner to greatly magnify the drug discovery and development effort nationally. Cytotoxic Anticancer Drugs: Models and Concepts for Drug Discovery and Development represents a forum which will become the major mode for bringing together these three different components in the equation to regularly discuss new results and ideas.

Over the past decade, techniques have been developed and implemented to observe metabolism noninvasively in localized regions of intact, living experimental animals and humans through the use of magnetic resonance spectroscopy (MRS). At the same time, magnetic resonance imaging (MRI) techniques developed in the 1970s and refined in this decade have been increasingly applied as a powerful clinical tool to probe human anatomy. Because of the unusual metabolic and physiologic characteristics of malignant tissues, oncology has been one of the primary focuses of the application of both MRS and MRI. Although considerable progress has been made in oncologic applications of magnetic resonance (MR), further research is needed to realize the full potential of MR in this area. Consequently, the 21st Annual Detroit Cancer Symposium entitled "Magnetic Resonance in Experimental and Clin ical Oncology" was organized to provide a forum for researchers in the field to report the state of the art of MRS and MRI in oncol ogy, to discuss future goals for MRS and MRI in oncology, and to define the research needed to meet those goals. The major emphasis of the symposium was on MRS due to both the recent widespread availability of clinical MRS instrumentation and the extensive amount of animal MRS research performed over the past half decade."

Biochemical Modulation at the present time defines an area of study in which the intracellular metabolism of a given anti cancer agent is modulated (usually by a noncytotoxic agent or a cytotoxic agent at sufficiently low dosage to make it non cytotoxic) in order to either increase the effectiveness of the particular agent against tumor cells or decrease its cytotox icity against normal cells. The major focus of modulation has been the agents 5-fluorouracil (FUra), arabinofuranosylcytosine (ara-C), methotrexate (MTX) and a few alkylating agents. The major thrust of the studies has been to increase the flow of the anticancer agent along the pathway responsible for the formation of the cytotoxic species: for example, FUra to FUTP or ara-C to ara-CTP. While in most cases the application of research re sults to clinical trials does not require the subsequent exper tise of the laboratory researchers, application of biochemical modulatory schemes to clinical protocols necessitate a dramatic break with the past procedures. As shown in the laboratory clinical loop below, close collaboration between the laboratory and clinical investigator is essential. While the laboratory REDEFINE TECHNOLOGY, TESTS OR QUESTIONS FOR FURTHER THERAPEUTIC ADVANCE CLINICAL EXPERIMENTAL PROTOCOL (LABORATORY) RESEARCH STUDIES DEFINE AND TEST APPROPRIATE SCIENTIFIC PARAMETERS results define rationally-based regimens, it is essential that the clinical protocols contain the requirement that clinical material (either tumor or normal tissues) be sampled to deter mine whether the biochemical modulation being proposed is in fact beinq accomplished."

This year notes two major changes in the annual Detroit Cancer Symposium. The first is our intention of selecting top ics of broad interest to the cancer community and examining the subject from both a basic laboratory and clinical viewpoint. In this way, the importance of both elements of cancer research are noted and the interplay between them emphasized. Further, we believe that Symposia such as this act to stimulate the basic scientist and clinician to continue their studies with the know ledge of the impact that each has upon the other and the nec essary cooperation required to solve the cancer problem. The second change is the publication of this Symposium. The pre vious sixteen were not committed to manuscript form. Given the change in format and intent of the series, we believe that this and subsequent volumes will make important contributions to the cancer literature. The topic of "Biology and Therapy of Acute Leukemia" was chosen for the first Symposium because of its historical signif icance in cancer chemotherapy. The therapeutic rationale for human leukemia is the result of understanding the basic tumor biology largely derived from transplantable leukemias in exper imental animals. It is through these models, as discussed by Dr. Fred Valeriote, that we learned the cellular kinetics of leukemia, the antileukemic effects of new agents and the ef fect of growth perturbation by various chemotherapeutic agents and their combinations."