The Search for New Anticancer Drugs
Most of the anti-cancer drugs in use today were discovered by happy accident rather than design, yet the rational design of better anti-cancer drugs remains a cherished goal, and one of the most important challenges facing medical science. This book repre
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CANCER BIOLOGY AND MEDICINE Series Editors M.
J.
Waring and B. A.
J.
Ponder
THE SEARCH FOR NEW ANTICANCER DRUGS Edited by
M. J. Waring Reader in Chemotherapy, University of Cambridge, UK and
B. A. J. Ponder Director, CRC Human Cancer Genetics Research Group, Department of Pathology, University of Cambridge, UK
KLUWER ACADEMIC PUBLISHERS
DORDRECHT/BOSTON/LONDON
Distributors for the United States and Canada: Kluwer Academic Publishers, PO Box 358, Accord Station, Hingham, MA 02018-0358, USA for all other countries: Kluwer Academic Publishers Group, Distribution Center, PO Box 322, 3300 AH Dordrecht, The Netherlands
A catalogue record for this book is available from the British Library ISBN-13: 978-94-010-6659-4 e-ISBN-13: 978-94-009-0385-2 DOl: 10.1007/978-94-009-0385-2
Library of Congress Cataloging in Publication Data The Search for new anticancer drugs / edited by M. J. Waring and B. A. J. Ponder. p. cm. - (Cancer biology and medicine; 3) Includes bibliographical references and index. 1. Antineoplastic agents. 2. Cancer-Chemotherapy. I. Waring, Michael J. II. Ponder, B. A. J. (Bruce A. J.), 1944-. III. Series. [DNLM: 1. Antineoplastic Agents-therapeutic use. 2. Neoplasms-drug therapy. WI CA673L v. 3/ QZ 267 S439] RC271.C5S39 1992 616.99'4061-dc20 DNLMJDLC 92-49744 for Library of Congress CIP
Copyright (£j 1992 by Kluwer Academic Publishers
Softcover reprint of the hardcover 1st edition 1992
All right reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without prior permission from the publishers, Kluwer Academic Publishers BV, PO Box 17,3300 AA Dordrecht, The Netherlands. Published in the United Kingdom by Kluwer Academic Publishers, PO Box 55, Lancaster, UK. Kluwer Academic Publishers BV incorporates the publishing programmes ofD. Reidel, Martinus Nijhoff, Dr W. Junk and MTP Press. Typeset by Expo Holdings Sdn. Bhd., Malaysia.
Contents vi
List of Contributors Preface
1.
Vll
Is there a future for the small molecule in developmental cancer chemotherapy? M. F. G. Stevens
2. The role of medicinal chemistry in the discovery of DNA-active anticancer drugs: from random searching, through lead development, to de novo design
W.A.Denny
3. In vitro systems for anticancer drug testing G.J. Finlay
4. Tumour hypoxia: challenges for cancer chemotherapy W. R. Wilson
5. Computer modelling and drug design S. Neidle and C. A. Laughton
19 55 87 133
6. Differentiation inducers and their potential use in the treatment of acute myelogenous leukaemia
A. Tobler and H. P. Koeffier
7. Angiosuppression
163 183
T.-P D. Fan and S. Brem
8. Preclinical evaluation and phase I trials I. R. Judson
9. Evaluation: how should a new treatment be evaluated? J. G.McVie
10. Oncogene-targeted antisense oligonucleotides: tools for genetic analysis or new anticancer drugs? E. Saison-Behmoaras and C. Helene Index
v
229 245 259 277
List of Contributors
S.BREM Division of Neurosur
