ANTICANCER DRUG DISCOVERY AND DEVELOPMENT: NATURAL PRODUCTS AND NEW MOLECULAR MODELS

Developments in Oncology

52. M. Chatel, F. Darcel and I. Pecker (eds.): Brain Oncology. Biology, Diagnosis and Therapy. 1987 ISBN 0-89838-954-2

53. M.P. Hacker, I.S. Lazo and T.R. Tritton (eds.): Organ Directed Toxicities of Anticancer Drugs. 1988 ISBN 0-89838-356-0

54. M. Nicolini (ed.): Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy. 1988 ISBN 0-89838-358-7

55. I.R. Ryan and L.O. Baker (eds.): Recent Concepts in Sarcoma Treatment. 1988 ISBN 0-89838-376-5

56. M.A. Rich, I.C. Hager and D.M. Lopez (eds.): Breast Cancer. Scientific and Clinical Aspects. 1988 ISBN 0-89838-387-0

57. B.A. Stoll (ed.): Women at High Risk to Breast Cancer. 1989 ISBN 0-89838-416-8

58. M.A. Rich, I.C. Hager and I. Keydar (eds.): Breast Cancer. Progress in Biology, Clinical Management and Prevention. 1989 ISBN 0-7923-0507-8

59. P.I. Reed, M. Carboni, B.I. Iohnston and S. Guadagni (eds.): New Trends in Gastric Cancer. Background and Videosurgery. 1990 ISBN 0-7923-8917-4

60. H.K. Awwad: Radiation Oncology: Radiobiological and Physiological Perspectives. The Boundary-Zone between Clinical Radiotherapy and Fundamental Radiobiology and Physiology. 1990 ISBN 0-7923-0783-6

61. I.L. Evelhoch, W. Negendank, F.A. Valeriote and L.H. Baker (eds.): Magnetic Resonance in Experimental and Clinical Oncology. 1990 ISBN 0-7923-0935-9

62. B.A. Stoll (ed.): Approaches to Breast Cancer Prevention. 1991 ISBN 0-7923-0995-2

63. M.J. Hill and A. Giacosa (eds.): Causation and Prevention of Human Cancer. 1991 ISBN 0-7923-1084-5

64. I.R.W. Masters (ed.): Human Cancer in Primary Culture. A Handbook. 1991 ISBN-O-7923-1088-8

65. N. Kobayashi, T. Akera and S. Mizutani (eds.): Childhood Leukemia. Present Problems and Future Prospects. 1991 ISBN 0-7923-1138-8

66. P. Paoletti, K. Takakura, M.D. Walker, G. Butti and S. Pezzotta (eds.): Neuro-oncology. 1991 ISBN 0-7923-1215-5

67. K.V. Honn, L.J. Marnett, S. Nigam and T. Walden Ir. (eds.): Eicosanoids and Other Bioactive Lipids in Cancer and Radiation Injury. 1991

ISBN 0-7923-1303-8 68. F.A. Valeriote, T.H. Corbett and L.H. Baker (eds.): Cytotoxic Anticancer

Drugs: Models and Concepts for Drug Discovery and Development. 1992 ISBN 0-7923-1629-0

69. L. Dogliotti, A. Sapino and G. Bussolati (eds.): Breast Cancer. Biological and Clinical Progress. 1992 ISBN 0-7923-1655-X

70. E. Benito, A. Giacosa and M.I. Hill (eds.): Public Education on Diet and Cancer. 1992 ISBN 0-7923-8997-2

71. S. Nigam, K.V. Honn, L.J. Morvett and Th.L. Walden, Ir. (eds.): Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation and Radiation Injury. 1992

ISBN 0-7923-1870-6 72. F.H. Menko: Genetics of Colorectal Cancer for Clinical Practice. 1993

ISBN 0-7923-2100-6 73. R.P. Gallagher and I.M. Elwood (eds.): Epidemiological Aspects of Cutaneous

Malignant Melanoma. 1994 ISBN 0-7923-2740-3

SPRINGER SCIENCE+BUSINESS MEDIA, LLC

ANTICANCER DRUG DISCOVERY AND DEVELOPMENT: NATURAL PRODUCTS AND NEW MOLECULAR MODELS

Proceedings of the Second Drug Discovery and Development Symposium Traverse City, Michigan, USA - June 27-29, 1991

Edited by

Frederick A. Valeriote Thomas H. Corbett Laurence H. Baker

Wayne State University School of Medicine Detroit, Michigan

~.

" Springer Science+Business Media, LLC

Distributors for North America: Kluwer Academic Publishers 101 Philip Drive Assinippi Park Norwell, Massachusetts 02061 USA

Distributors for all other countries: Kluwer Academic Publishers Group Distribution Centre Post Office Box 322 3300 AH Dordrecht, THE NETHERLANDS

Library of Congress Cataloging-in-PublicatioD Data

A C.I.P. Catalogue record for this book is available from the Library of Congress.

ISBN 978-1-4613-6118-3 ISBN 978-1-4615-2610-0 (eBook) DOI 10.1007/978-1-4615-2610-0

Copyright ~ 1994 Springer Science+Business Media New York Originally published by Kluwer Academic Publishers in 1994 Softcover reprint of the hardcover 1 st edition 1994 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photo-copying, recording, or otherwise, without the prior written permission of the publisher, Springer Science+Business Media, LLC.

Printed on acid-free paper.

CONTENTS

1. DISCOVERY OF NATURAL PRODUCTS FROM MICROALGAE AND MARINE ORGANISMS

Fred Valeriote. Richard E. Moore. Gregory M.l. Patterson. Valerie J. Paul. Paul J. Scheuer. and Thomas Corbett

2. DISCOVERY OF NATURALLY OCCURRING ANTITUMOR AGENTS 27 Ching-Jer Chang. Curtis l. Ashendel. Robert l. Geahlen. and Jerry l. McLaughlin

3. MARINE INVERTEBRATES AND MICROBES AS SOURCES OF POTENTIAL ANTITUMOR COMPOUNDS 39

Andrew l. Staley and Jon Clardy

4. NOVEL STRATEGIES FOR THE DISCOVERY OF PLANT-DERIVED ANTICANCER AGENTS 63

Geoffrey A. Cordell. Norman R. Farnsworth. Christopher W.W. Beecher. D. Doel Soejarto. A. Douglas Kinghorn. John M. Pezzuto. Monroe E. Wall. Mansukhlal C. Wani. Ronald R. Cobb. Melanie J. O·Neili. R. Murray Tait. and Timothy J.R. Harris

5. A STRATEGY FOR IDENTIFYING NOVEL INHIBITORS OF DNA TOPOISOMERASE I 85

Sidney M. Hecht. David E. Berry. Laurie J. Mackenzie. Elva A. Shultis. and James A. Chan

6. AL TROMYCINS: A NEW FAMILY OF ANTITUMOR ANTIBIOTICS-DISCOVERY AND BIOLOGICAL EVALUATION 95

J.B. McAlpine. J.P. Karwowski. M. Jackson. G.M. Brill. S. Kadam. l. Shen. J.J. Clement. J. Alder. and N.S. Burres

7. SUPPRESSION OF HUMAN MELANOMA METASTASIS IN SCID MICE WITH ANTIBODIES TO THE EGF-RECEPTOR 119

B.M. Mueller and R.A. Reisfeld

8. GROWTH FACTOR AND ONCOGENE SIGNALLING AS A TARGET FOR ANTICANCER DRUG DEVELOPMENT 127

Garth Powis

VI

9. NUCLEOSIDE AND NUCLEOTIDE MODULATION OF ONCOGENIC EXPRESSION: A NEW APPROACH TO CANCER CHEMOTHERAPY 149

Roland K. Robins. Rick A. Finch. and Thomas l. Avery

10. INTERFERONS IN CANCER THERAPY: FROM CLINICAL TRIALS TO NEW POTENTIALS IN ANTICANCER DRUG DISCOVERY AND 183 DEVELOPMENT

Gerhard G. Steinmann. Gunther R. Adolf. and Gerhard Leitz

11. SELECTION AND MANIPULATION OF IMMUNOGLOBULINS FOR RADIONUCLIDE DELIVERY 209

Z. Steplewski. P. Curtis. J. Hainfeld. R. Mease. and S. Srivastava

12. MICROORGANISMS: STRATEGIC SOURCES OF NOVEL ANTI-TUMOR AGENTS 235

Josefino B. Tunac

13. THE THERAPEUTIC POTENTIAL OF NOVEL PURE ANTIESTROGENS 269 A.E. Wakeling

14. PRECLINICAL PHARMACOLOGY AND PHASE I CLINICAL TRIALS OF TAXOTERE (RP 56976. NSC 628503) 283

Marie-Christine Bissery. Howard Burris. and Richard Pazdur

15. BROPI RIMINE. A SMALL-MOLECULE BIOLOGICAL RESPONSE MODIFIER AND AN EFFECTIVE ANTITUMOR AGENT 299

li H. li

16. DETERMINANTS OF ETOPOSIDE CYTOTOXICITY IN VITRO Richard B. Lock

17. SCREENING FOR ANTICANCER LEADS FROM MARINE ORGANISMS IN

347

A MECHANISM-BASED DRUG DISCOVERY PROGRAM 365 P. Crews. D.l. Slate. W.H. Gerwick. F.J. Schmitz. R. Schatzman. B. Strulovici. P. Cannon. and l.M. Hunter

LIST OF PARTICIPANTS

Laurence H. Baker. D.O. Division of Hematology and

Oncology Wayne State University P.O. Box 02188 Detroit. MI 48201

Bijoy K. Bhuyan. Ph.D. Cancer Research The Upjohn Company 7000 Portage Road Kalamazoo. MI 49001

Marie-Christine Bissery. Ph. D. Anticancer Research Programme Rhone-Poulenc Centre de Recherches de Vi try 13 Quai Jules Guesde B.P. 14 - 94403 Vi try Sur Seine Cedex. France

William G. Bornmann. Ph.D. Department of Chemistry The University of Vermont Cook Physical Science Building Burlington. VT 05405

Michael Brattain. Ph.D. Baylor College of Medicine One Baylor Plaza Houston. TX 77030

Howard A. Burris. III. M.D. Brooke Army Medical Center Fort Sam Houston. TX 78234

Ching-jer Chang. Ph.D. Department of Medicinal

Chemistry and Pharmacognosy Purdue University West Lafayette. IN 47907

Michaele Christian. M.D. Developmental Chemotherapy

Section Investigational Drug Branch CTEP-DCT 6130 Executive Bvld. Executive Plaza North. Rm. 715 Rockville. Maryland 20852

John Clardy. Ph.D. Department of Chemistry Baker Laboratory Cornell University Ithaca. NY 14853

Geoffrey A. Cordell. Ph.D. College of Pharmacy University of Illinois at

Chicago 833 S. Wood St .• mlc 781 Chicago.IL 60612

Philip Crews. Ph.D. Chemistry Board of Studies University of California 1156 High Street Santa Cruz. CA 95064

Michael Grever. M.D. National Cancer Institute Executive Plaza North Suite #843 Bethesda. MD 20892

Louise B. Grochow. M.D. Johns Hopkins Oncology Center Pharmacology Laboratory 600 North Wolfe Street Baltimore. MD 21205

viii

Sidney M. Hecht. Ph.D. Department of Chemistry University of Virginia Charlottesville. VA 22901

Dr. Roland Henrar New Drug Development Office Free University Hospital De Boelelaan 1117 NL-1081 HV Amsterdam. The Netherlands

Randall K. Johnson. Ph.D. Department of Biomolecular

Discovery Smith Kline Beecham

Pharmaceuticals 1500 Spring Garden Street P.O. Box 7929 Philadelphia. PA 19101

Li H. Li. Ph.D. Cancer Research Department The Upjohn Company 301 Henrietta Street Kalamazoo. MI 49001

James B. McAlpine. Ph.D. Anti-Infective Research

Division Abbott Laboratories Abbott Park. IL 60064

Barbara M. Mueller. Ph.D. Research Institute of Scripps Clinic IMM-13 10666 N. Torrey Pines Road La Jolla. CA 92037

+ deceased

Richard Pazdur. M.D. Section of Digestive Disease and Gastrointestinal Oncology Division of Medicine - 92 The University of Texas M.D. Anderson Cancer Center 1515 Holcombe Blvd. Houston. TX 77030

Elizabeth Poplin. M.D. Division of Hematology and

Oncology Wayne State University P.O. Box 02188 Detroit. MI 48201

Garth Powis. D.Phil. Arizona Cancer Center 1515 North Campbell Avenue Tucson. Arizona 85724

Roland K. Robins. Ph .0. +

Department of Pharmacology School of Medicine University of California. San Diego 11077 N. Torrey Pines Road La Jolla. CA 92037

Gerhard G. Steinmann. M.D. Karl Thomae. Gmbh Experimental Cytology Dept. P.O. Box 1755.0-7950 Biberach. Germany

Zenon Steplewski. M.D .• Ph.D. The Wistar Institute 36th and Spruce Streets Philadelphia. PA 19104

Matthew Suffness, Ph.D. Executive Plaza North Developmental Therapeutics

Program Division of Cancer Treatment National Cancer Institute Room #832 Bethesda, MD 20892

Josefino Tunac, Ph.D. Fermical Suite #338 2727 Second Avenue Detroit, MI 48201

Richard l. Tuttle, Ph.D. Cancer Therapy and Tumor

Biology Sections Burroughs WeUcome Company 3030 Cornwallis Road Research Triangle Park, NC 27709

Manuel Valdivieso, M.D. Division of Hematology and

Oncology Wayne State University P.O. Box 02188 Detroit, MI 48201

Frederick A. Valeriote, Ph.D. Division of Hematology and

Oncology Wayne State University P.O. Box 02188 Detroit, MI 48201

Alan Wakeling. Ph.D. ICI Pharmaceuticals Alderly Park Macclesfield, Cheshire United Kingdom SK20 4TG

Anton Wellstein, M.D., Ph.D. Lombardi Cancer Research Center Georgetown University 3800 Reservoir Road, N.W. Washington, D.C. 20007

IX

ACKNOWLEDGMENTS

Generous support from the following donors were critical to the success of this Symposium:

- American Cyanamid - Amgen - Bristol-Myers - Cetus Corporation - Glaxo Pharmaceuticals (Division of Glaxo, Inc.) - Harper Hospital - Hoechst-Roussel Pharmaceuticals, Inc. - Immunex Corporation - lederle Laboratories - Schering Corporation - Sterling Drug, Inc. (Subsidiary of Eastman Kodak Company) - Upjohn Company - Wayne State University lupiloff Endowment

Editorial assistance and typing was provided by Claudia A. Valeriote.