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TIMELINE

Natural products in cancer

chemotherapy: past, present and future
John Mann
Natural products have been the mainstay of
cancer chemotherapy for the past 30 years.
However, the quickening pace of (aberrant)
gene identification, and the new
technologies of combinatorial chemistry
and high-throughput screening, should
provide access to a wide range of new,
totally synthetic drugs. Will these new
approaches sound the death knell for
therapies based on natural products? In
reality, natural products are likely to provide
many of the lead structures, and these will
be used as templates for the construction
of novel compounds with enhanced
biological properties.

How long have we been using plant extracts

to treat cancer 1,2? The American Indians
used extracts from the roots of mayapple,
Podophyllum peltatum (FIG. 1a), as an effective treatment for skin cancers and venereal
warts. The main constituent, podophyllotoxin, was the forerunner of the group of
anticancer agents known as the
podophyllins, which includes etoposide and
teniposide. Similarly, the plant Catharanthus
roseus (FIG. 1b; also known as Vinca rosea or
the rosey periwinkle) was used (probably
without efficacy) as a hypoglycaemic agent
in many parts of Asia, but it was not until
1958 that its main constituents, vinblastine
and vincristine, were found to have potent
cytotoxic properties. These agents have
contributed significantly to the successful
treatment of many cancers.
These discoveries inspired by folk
medicine encouraged the National

Cancer Institute (NCI) to begin a large-scale

screening programme for antitumour
agents3,4 in 1960. Between 1960 and 1982,
35,000 plant samples were evaluated
primarily against the mouse leukaemia cell
lines L1210 and P388. The most significant
drug to emerge from this massive programme was paclitaxel (Taxol), obtained
from the bark of the Pacific yew Taxus brevifolia. In 1985, the NCI began a new programme in which extracts from plants,
animals and microorganisms (increasingly,
those of marine origin) are screened against
a panel of 60 human cancer cell lines,
including those from solid tumours (lung,
colon, skin, kidney, ovary, brain, breast and
prostate), as well as several leukaemias. This
programme should detect compounds that
are active against solid tumours but not
against leukaemias, which would have been
missed in the original screen. What types of
compound have been found to have activity
against cancer cells in these types of screen?
The following sections are intended to
provide a flavour of promising compounds
identified from a range of sources, rather
than a comprehensive list.
Plants as a source of anticancer drugs

Vinblastine and vincristine were first introduced in the late 1960s and have
contributed to long-term remissions and
cures with childhood leukaemia, testicular
teratoma, Hodgkins disease and many
other cancers. Several structural analogues are
also in clinical use, and most notable of these
are vinorelbine and vindesine5. Etoposide is in

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regular use for the effective treatment of testicular teratoma and small-cell lung cancer,
whereas teniposide has efficacy against acute
lymphocytic leukaemia and neuroblastoma
in children, and against non-Hodgkins
lymphomas and brain tumours in adults.
Much recent synthetic work has concentrated
on the design of more water-soluble
analogues6. But the undoubted star is Taxol,
which shows efficacy against refractory breast
and ovarian cancers. It is, at present, the bestselling anticancer drug; sales reached US $1.5
billion in 2000 and are still growing7. But it
took 20 years from its discovery in 1967 to the
first real clinical responses observed with ovarian cancer in 1987, and even longer until its
potential in refractory breast cancer was realized. Why did it take so long to reach the
clinic? The early supply problems were enormous. About 4,000 Pacific yew trees (FIG. 2a)
had to be sacrificed for their bark to provide
360 g of Taxol for the early clinical trials, and
this rose to 38,000 trees for 25 kg of Taxol
needed to treat 12,000 patients in the early
1990s. These difficulties were solved when it
was discovered by Potier and co-workers that
the foliage of the European yew, Taxus baccata,
contained greater amounts of a related chemical structure, 10-deacetylbaccatin III, that
could easily be converted into Taxol and into
the more potent analogue taxotere8. In 1979,
Susan Horwitz and colleagues showed that the
mode of action of Taxol was different from
that of any other anticancer agent in clinical
use at the time. Unlike vinblastine and vincristine, which destabilize microtubules, Taxol
stabilizes them during cell division9. This
allowed structureactivity relationships to be
established for hundreds of semi-synthetic
analogues, with the result that several morepotent analogues are already in clinical trials10.
The natural product, paclitaxel, has therefore
provided not only an effective drug, but also
the springboard for further developments. It
has also been the object of commercial and
political controversy, not least when BristolMyers Squibb was given permission to patent
the name Taxol, depriving the scientific

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clinical trial. These are early days for this new

class of antitumour agent and there will
undoubtedly be further optimization of
their structureactivity profiles.

Antitumour agents from marine sources

Figure 1 | Two of the earliest plants to yield natural products with anticancer activities.
a | Podophyllum peltatum (the mayapple), which produces podophyllotoxin, and b | Catharanthus
roseus (also known as Vinca rosea or the rosy periwinkle), which produces the Vinca alkaloids
vinblastine and vincristine.

community of the name of a natural product.

This led to some furious exchanges in the literature, perhaps most famously when a
spokesman from Bristol-Myers Squibb
responded to a critical editorial in Nature with
an admonishment that the journal had stolen
its trademark from Mother Nature11.
Camptothecin, from the Chinese ornamental tree Camptotheca accuminata, had a
similarly long gestation period. Its early
promise in the 1970s was blighted by severe
bladder toxicity, but chemical manipulation
of its structure subsequently produced analogues, including topotecan (Hycamptin)
and irinotecan (Camptosar), that have been
approved for clinical use12. These days
camptothecin is valued as a biological tool
to understand the functions of the enzyme
topoisomerase I, for which it is a specific
inhibitor. This enzyme is intimately
involved in the unwinding of DNA before
transcription and replication, and camptothecin and its structural analogues will
not only help to unravel these complex
processes but also act as lead structures for
the design of other molecules that selectively inhibit topoisomerases13.
Anticancer drugs from microbes

Microorganisms have been the principal

source of antibacterial agents, but they have
also provided some of the key drugs for
cancer chemotherapy. Most notable are the
bleomycins (Blenoxane), dactinomycin,
mitomycin C, and the anthracyclinones
daunomycin and doxorubicin (adriamycin).

144

All of these were introduced to the clinic

before their modes of action had been
determined, and whereas most of them
probably damage DNA through the formation of free-radical intermediates, there is
growing evidence that analogues could be
produced with more specific modes of
action. For example, Hecht and colleagues
have revealed that the bleomycins probably
target amino-acid transfer RNAs, and are
using combinatorial methods to prepare
libraries of bleomycin analogues with the
aim of identifying novel structures with
complete specificity for tRNA14.
But the best example of a new class of
antitumour drugs from a microorganism is
the epothilones. They were first isolated by
Hofle in 1993 from the myxobacterium
Sorangium cellulosum15. Once their structures were revealed in 1996, epothilones
AD soon succumbed to total synthesis16,17.
They have a similar mode of action to Taxol
stabilization of microtubules during cell
division but offer the twin advantages of
greater water solubility and availability by
fermentation technology. The natural products epothilone A and B might have too
narrow a therapeutic index, but access to the
basic skeleton through synthesis has allowed
the production of a range of analogues using
combinatorial methodology18,19. The most
promising of these are 12, 13-desoxyepothilone B and 15-aza-epothilone B19,
which have activity at least as great as Taxol
against a range of tumour cell lines. One of
these analogues has recently entered a Phase I

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Until the mid-1960s, investigation of natural

products from marine organisms was essentially non-existent. Since then, ~10,000 new
structures have been isolated from marine
microorganisms, seaweeds, sponges, soft
corals, and marine invertebrates, such as
bryozoans, echinoderms, molluscs and
ascidians20,21. In the past 30 years, more than
300 patents have been issued covering
potential anticancer agents from the sea, but
as yet no marine natural product has been
licensed for clinical use as an anticancer
agent22. However, that situation might soon
change because at least ten compounds are
in various stages of clinical trials. The most
promising of these is bryostatin 1, which is
isolated from the bryozoan Bugula neritina,
and has activity against a range of cancers.
As with most natural products of marine
origin, enormous difficulties are associated
with the collection of material (from an
often hostile environment) and with the low
concentrations that are present in the
organisms. For example, a 1,000-kg sample
of wild (and still damp) B. neritina from the
waters off Southern California might yield
1.5 g of bryostatin 1, and perhaps 2 g of
other members of the family. Commercial
aquaculture is being investigated23 and a
successful aquaculture unit might yield
100200 g per year at a cost of $700,000.
Aquaculture might provide the solution to
the supply problem, but does not provide
analogues with enhanced potency or greater
selectivity. However, this goal can be
achieved through chemical synthesis of the
basic molecular skeleton, and then using
this as a template for combinatorial chemistry coupled with high-throughput screening to identify novel structures with the
appropriate biological attributes24,25. This
approach will always have a greater chance
of success than can be expected from the
construction of huge speculative structural
libraries, simply because nature has provided clues as to the structural requirements
for biological activity.
Although its mode of action at the molecular level remains poorly understood, bryostatin 1 induces several cellular responses,
including stimulation of the immune system, increased expression of p53, and
induction of apoptosis in cancer cells. Many
of these activities are probably associated
with interaction of the natural product with

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Figure 2 | Some of natures combinatorial chemists. a | The pacific yew, Taxus brevifolia (courtesy of
Nancy Lankford and the United States National Cancer Institute). b | Bugula neritina (courtesy of Karen
Gowlett-Holmes). c | Scanning electron micrograph of Sorangium cellulosum (courtesy of the Gesellschaft
fr Biotechnologische Forschung, Braunschweig, Germany).

various protein kinase C isozymes26. To

explore structureactivity relationships,
synthetic chemists have produced a range of
analogues based on the basic skeleton of
bryostatin. Wenders group, which has carried
out much of the research on bryostatin 1,
recently reported a series of much simplified
structures with potent in vitro antitumour
activity27,28. Bryostatin 1 is being evaluated in
about 50 Phase I and Phase II clinical trials
against melanoma, leukaemias, lymphomas,
and cancers of the breast, prostate, lung, kidney, cervix, ovary, oesophagus and stomach.
So far, there have been no complete remissions, but some patients have experienced
stabilization of disease for almost two years,
and the new analogues might offer greater
bioavailability, potency and selectivity.
Two classes of structurally similar marine
natural products from soft coral are also
causing a great deal of excitement. These are
the sarcodictyins from the Mediterranean
coral Sarcodictyon roseum 29, first isolated in
1987, and eleutherobin from coral
(Eleutherobia spp.), found off the coast of
Western Australia in 1994 (REF. 30). These
compounds also have Taxol-like activity, with
eleutherobin showing up to 50 times more
potency than Taxol against a range of cancer
cell lines in vitro. The synthetic chemists were
soon in action and eleutherobin was synthesized by the groups of Nicolaou and

Danishefsky31,32. Furthermore, Nicolaous

group has produced a large library of sarcodictyin analogues using solid- and solutionphase combinatorial methods, and is
exploring structureactivity trends33 (FIG. 3).
These compounds will almost certainly have
to be synthesized because aquaculture of the
corals is unlikely to be a viable alternative.
Marine natural-product chemistry has
come a long way since the Caribbean sponge
Cryptotheca crypta provided several antiviral
compounds in the 1950s, which in turn acted
as structural templates for the production of
the antimetabolite Ara-C (cytosine arabinoside) in 1959. Given the enormous diversity of life in the oceans, it is certain that other
novel marine natural products will be identified and shown to have useful antitumour
activity, and this vast repository of esoteric
structures will always complement terrestrial
combinatorial chemistry.
Targeting natural products

Caesar Milsteins pioneering work34 on the

production of monoclonal antibodies led to
a new approach to targeting cancer cells in
the 1980s. Later in the same decade,
Kenneth Bagshawe and Peter Senter developed an approach that combined this new
means of tumour targeting with natural
products: antibody-directed enzyme-prodrug
therapy (ADEPT; FIG. 4a). This technique

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uses an antibody specific for a tumour cell

that is conjugated to an enzyme35 . The conjugate is administered to the patient and, in
principle, it accumulates at the tumour site
as the antibodies bind to antigens on the
tumour cell surface. After a short period,
during which excess conjugate clears from
the system, a non-cytotoxic prodrug is
given and this is activated by the enzyme in
the antibodyenzyme conjugate to yield a
cytotoxic anticancer drug. In principle, the
cytotoxic agent is only revealed close to the
tumour cells, so nonspecific cytotoxicity is
reduced. The other advantage is that one
molecule of enzyme catalyses the production
of numerous molecules of drug. Many naturally occurring cytotoxic agents have been
converted into prodrugs, and for much of
the past decade they have been used with the
ADEPT technology more as experimental
tools than as clinically viable drugs.
One of the earliest examples involved
doxorubicin attached to a cephalosporin,
which was subsequently cleaved when the
prodrug reacted with antibody-bound
-lactamase. The same strategy was used to
release Vinca alkaloids and Taxol from
cephalosporinalkaloid prodrugs36. Antibodies have also been conjugated to carboxypeptidase G2, cytosine deaminase, and
penicillin G and V amidases (which, like -lactamases, have no mammalian homologue),
and also to enzymes of non-mammalian origin, such as -glucuronidase, that also have
mammalian counterparts. Some striking
results have been seen in mice with cancer-cell
xenografts, but until recently no significant
results had been seen in humans.

Side chain is
important for activity
O
O

N CH3

Both nitrogens
are necessary
for activity

O
H
O

OH
O
CH3

Can be substituted
for a ketal group
without loss of activity

Esters have higher activity than

amides; reduction of the ester to
the acohol leads to loss of activity

Figure 3 | Structureactivity relationships for

the sarcodictyins. This example shows how
altering the structure of a naturally occurring
compound with activity against cancer cells can
markedly change its activity. Altering the structure
of the highlighted side chains can lead to
differences in cytotoxic activity of >1,000-fold.
Modified from REF. 33.

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a ADEPT

b Mylotarg
Antibody against CD33

Neighbouring
cell

Drug
Death

Plasma membrane
CD33

Prodrug

Tumour cell

Enzyme

Endosome
Cleavage

Antibody

Tumour
antigen

Damage

Active drug

Death

Nucleus

c Neuropeptide Y
Drug
Death

NPY
NPY receptor

Endosome

Cleavage
Damage

Death

Figure 4 | Targeting natural products with antibodies and peptide hormones. a | Antibody-directed
enzyme prodrug therapy (ADEPT). An antigen expressed on tumour cells binds an antibodyenzyme
conjugate. A prodrug is then administered and is converted to an active cytotoxin only in the environs of
the tumour. b | The strategy behind Mylotarg. The tumour antigen in this case, CD33 on leukaemia
cells binds a humanized antibody to CD33 that is conjugated to a cytotoxin, calicheamycin. The
antibodycalicheamycin conjugate is internalized and releases the drug, which causes DNA damage and
activates p53-mediated apoptosis. c | Killing neuroblastoma cells by targeting the neuropeptide Y (NPY )
receptor. In this case, the principle is the same as for Mylotarg but the tumour-cell antigen is the NPY
receptor, and the drug (in this case, an anthracyclinone) is conjugated to NPY.

This might now change with the launch of

gemtuzumab ozogamicin (Mylotarg; FIG. 4b)37
by Celltech and Wyeth-Ayerst in May 2000.
Mylotarg is a conjugate of a humanized
monoclonal antibody that targets the CD33
antigen on leukaemia cells with a prodrug
form of the natural product calicheamicin.
Once bound to the leukaemia cells, the conjugate is internalized and then breaks down,
allowing calicheamicin to target a specific
region of the minor groove of DNA. Here, it
undergoes a chemical transformation to produce a benzene diradical that induces double-strand breaks and, ultimately, cell death.
As the CD33 antigen is not expressed on
normal haematopoietic cells, the antibodycalicheamicin conjugate has a high
degree of selectivity for the leukaemic cells.
Results of Phase II studies in the United
States showed that Mylotarg had an overall
response rate of 34% in patients under 60
years of age and 26% in those over 60 years of
age who had relapsed following initial
chemotherapy for acute myeloid leukaemia.
These results are important because they
show that the original ADEPT technology
can be simplified if discrete tumour-cell

146

antigens can be recognized, and humanized

antibodies then produced. In addition, the
growing understanding of the modes of
action and exquisite selectivities of many
natural products should allow the design of
other antibodyprodrug conjugates. A similar strategy using cell-surface-selective
polypeptideprodrug conjugates has also
been described recently38. Here, advantage is
taken of the fact that many neuroblastomas
overexpress receptors for neuropeptide Y
(FIG. 4c). Conjugates of the anthracyclinone
drugs daunorubicin or doxorubicin with
neuropeptide Y bind to and are internalized
by a human neuroblastoma cell line. After
internalization and release, the anthracyclinones cytotoxicity is comparable to that of
the free drug.
The evolution of screening

A new strategy for using natural products is

emerging (BOX 1). In the past, natural products
with cytotoxic activity often entered the clinic
before any real understanding of their modes
of activity was appreciated. A recent example
of this would be the compound ecteinascidin
743 from the shallow-water tunicate

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Ecteinascidea turbinata, the synthesis of which

was first described by Corey and colleagues in
1996 (REF. 39), and which is undergoing clinical
evaluation against sarcomas and breast
tumours. But its mode of action is still completely unknown, and it does show a considerable level of toxicity. Most pharmaceutical
companies would no longer allow such an
empirical approach. They screen their natural
product extracts very carefully against purified enzymes and, in molecularly defined
assays, they try to exclude distracting molecules, such as tannins and saponins, thereby
increasing their chances of identifying compounds with genuine anticancer activity. At
this stage, numerous analogues are prepared
for extensive structureactivity relationship
studies, and a real effort can be made to elucidate the mode of biological activity, before
the choice of suitable pre-clinical candidates
is made. In this way, the drug that is finally
selected for clinical trials is more likely to
have beneficial effects with a minimum of
adverse side effects. Some of the pathways
for which potential anticancer compounds
have been identified are included in the
following sections.
Inhibitors of angiogenesis. Several natural
products have shown useful activity as
inhibitors of angiogenesis40; fumagillin from
the fungus Aspergillus fumigatus is probably
the best studied. More than ten years ago, its
inhibitory activity was shown but its associated toxicity precluded clinical evaluation.
However, its activity provided the basis for
the preparation of a range of structural
analogues. One of these TNP-470 (chloroacetylcarbamoylfumagillol)41 is effective
against a wide variety of tumours in vitro. It
has been the subject of Phase II and Phase III
trials with solid tumours, and a Phase I trial
against lymphomas and acute leukaemias. It
is well tolerated by patients with minimal
side effects. Its mode of action is obscure, but
there has been a recent demonstration that
fumagillin inhibits expression of the ETS1
transcription factor, which regulates the
expression of vascular endothelial growth
factors (VEGFs)42.
The combretastatins from the African
bush willow Combretum caffrum provide
a further example of native folk medicine
suggesting a lead compound43. Combretastatin
A-4, in the form of a soluble prodrug, has
shown selective toxicity against proliferating
endothelial cells in culture. The compound
produces a haemorrhagic necrosis at doses
that are no more than 10% of the maximum
tolerated dose. In Phase I clinical trials in the
United Kingdom and the United States, the

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drug also caused much necrosis but failed to
cause tumour regression. More recent results
using combinations of combretastain A-4
with cisplatin or 5-fluorouracil have
provided better results44,45.
Modifying cell signalling. The signalling
pathways that are upregulated in cancer cells
are an obvious target for rational drug
design, but have natural products been identified that target these pathways? Most of the
research in this area has been devoted to the
identification of agents that will inhibit a
specific protein kinase of a signalling pathway, and the RASRAFmitogen-activated
protein kinase kinase (MEK)extracellularsignal-regulated kinase (ERK) signalling
pathway has received most attention 46.
Several natural products have specific
inhibitory activity and are therefore useful
starting points for the design of more potent
molecules. For example, radicicol from the
microparasite Monocillium nordinii 47 acts as
a RAF destabilizer by binding to heat-shock
protein 90 (HSP90), which stabilizes RAF.
Lavendustin from Streptomyces griseolavendus 48
acts as a specific inhibitor of the epidermal
growth factor receptor (EGFR) protein tyrosine kinase, and has been used as a template
for the production of a range of analogues.
However, biological evaluation of these analogues indicated that their primary mode of
cytoxicity was through inhibition of tubulin
polymerization, and this might also be the main
activity of lavendustin. The staurosporines, also
from Streptomyces spp.49, seem to have many
modes of action. Novartis has taken one of the
numerous analogues that they have developed
from staurosporine (CGP41251) into the clinic
and this seems to inhibit protein kinase activity
and angiogenesis.
The future

Natural products or their structural relatives

still comprise about 50% of the drugs that are
used for cancer chemotherapy, and Taxol alone
is probably worth ~US $2 billion per annum to
Bristol-Myers Squibb. The information provided by the Human Genome Project will
undoubtedly identify gene targets for novel
anticancer drugs, and the pharmaceutical
industry will attempt to obtain these drugs
through the use of combinatorial chemistry
and high-throughput screening technologies.
But the production of vast libraries of compounds is unlikely to result in the identification
of the required new drugs. By contrast, the
much more subtle use of natural-product templates combined with chemistry to produce
selective analogues will have a much greater
chance of success. In a sense, we are accepting

Box 1 | The drug discovery pipeline

Most pharmaceutical companies now have the capability for fast-throughput screening, whereby
a new compound is tested for a range of biological activities ranging from cytotoxicity to
antibacterial, antiviral and anti-inflammatory activity. This testing is carried out with little
human intervention and robots report the positive hits automatically for further examination.
The compounds for these robotic screens are derived from three main sources: natural materials
(for example, plants, microorganisms and animals), regular chemical synthesis and
combinatorial chemistry. Combinatorial chemistry begins with a simple compound, usually
bound to an inert (polymeric) support, which is sequentially reacted with other chemical
entities before the final product is released from the support, purified and analysed. For
example, one of the 20 common amino acids might be attached to the support and then reacted
(in 20 separate reaction vessels) with the 20 possible amino acids, thereby providing a library of
20 dipeptides A1A1, A1A2, through to A1A20. Each of these is divided between 20 reaction
vessels and further reacted with the 20 amino acids, providing a library of 400 tripeptides
A1A1A1 through to A1A20A20. This technology (and related methods) can be used to produce
thousands of novel compounds for screening and these complement the smaller number of
compounds that are available from natural sources and conventional chemical synthesis.
From these thousands of compounds, a few hundred will show useful biological activity, and
careful analysis of the structureactivity relationships will usually indicate alternative structures
that should be prepared. Ultimately, some tens of drug candidates will progress through process
development, scale-up and toxicology, and a handful will make it into the clinic. The timescale for
these various stages is around five years from discovery to pre-clinical evaluation, and up to 12
years from discovery to launch of a drug into the market, at an overall cost of about 400 million.

that nature has already carried out the combinatorial chemistry; all we have to do is refine
the structures. A good example is provided by
the recent work of Nicolaou and colleagues33,
in which the basic skeleton of the cytotoxic
marine natural product sarcodictyin was
attached to a solid support, and this was used
as the template for the production of a 100compound library. Many of these new analogues had much greater cytotoxicities than the
parent compound, and several were up to 50
times more potent than Taxol.
Most of the natural products in clinical
use today were discovered through a routine
examination of terrestrial plants and micoorganisms, so serendipity is still an important
route of discovery. Our own recent work with
the Ghanaian medicinal plant Cryptolepsis
sanguinolenta, which had not hitherto shown
anticancer activity, revealed that the main
constituent, quindoline, had modest cytotoxic
activity50. More interestingly, this activity is
due to inhibition of the enzyme telomerase,
which is present in more than 90% of tumour
cells, but usually absent from normal cells.
Telomerase is the enzyme that maintains the
single-strand domains at the ends of chromosomes, and is, at present, a controversial target
for cancer chemotherapy51. Nonetheless, a
number of analogues of quindoline have now
been prepared, designed to bind more specifically to the enzyme. Several of these do have
enhanced inhibitory activity in a range of
tumours in vitro. Quindoline is therefore
another example of a natural product with
interesting antiproliferative activity, in which

NATURE REVIEWS | C ANCER

the basic skeleton can be used as a template

for the production of libraries of analogues
with potentially greater activity.
This coupling of synthetic chemistry with
the new technologies will take advantage of
natures gifts without exploitation of the
often delicate ecologies that support the parent organisms, and will ensure that natural
products make as many future contributions
to cancer chemotherapy as they have in the
past 35 years.
John Mann is at Queens University Belfast,
David Keir Building, Belfast BT9 5AG, Northern
Ireland. e-mail: j.mann@qub.ac.uk
DOI: 10.1038/nrc723
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Online links
DATABASES
The following terms in this article are linked online to:
CancerNet: http://cancernet.nci.nih.gov/
acute lymphocytic leukaemia | acute myeloid leukaemia |
brain tumours | breast tumours | cervical cancer | colon
tumours | Hodgkins disease | kidney tumours | melanoma |
neuroblastoma | non-Hodgkins lymphomas | oesophageal
cancer | ovarian tumours | prostate tumours | skin cancers |
small-cell lung cancer | stomach cancer | testicular teratoma
LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/
CD33 | EGFR | ERK | ETS1 | -glucuronidase | MEK |
neuropeptide Y | p53 | protein kinase C | RAF | RAS |
topoisomerase I | VEGFs
Medscape DrugInfo:
http://promini.medscape.com/drugdb/search.asp
Blenoxane | cisplatin | dactinomycin | doxorubicin |
etoposide | 5-fluorouracil | irinotecan | Mylotarg | Taxol |
taxotere | teniposide | topotecan | vinblastine | vincristine |
vinorelbine
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