ABOUT THIS PROJECT
Overview & Objective
Methodology & Search Strategy
Results (Ongoing: last update 6/04)


Overview & Objective


This is a unique database project of the Institute of East-West Medicine guided by an expert panel and under the direction of Dr. Raymond Chang , generously sponsored by the Gray Charitable Trust. The goal is to bring together materials from traditional Asian pharmacopoeias which have potential anti-cancer activity and to provide one unified source for such information with a special emphasis on translated results of laboratory, animal or human clinical experiments already published in native Asian journals or texts otherwise not easily accessible. The intent of all this is to encourage research and discovery which may hopefully lead to new cancer treatments.

Nature based treatments play an essential role in the healthcare of 80% of the world¡¯s population, and there is an expanding need for nature-based drug discovery to combat a serious disease such as cancer. Natural products with its vast molecular diversity and biological functionality remain a cornerstone of drug development for cancer. In the plant kingdom alone, there are greater than 250,000 species of plants out of which more than one thousand have been found to possess significant anticancer properties(1) . Between 1960-1981 for example, the US National Cancer Institute screened 114,000 extracts from 35,000 plants collected mainly in temperate regions and hundreds of compounds have been isolated from plant and marine source to date based on cytotoxicity assays(2) . Overall, it is estimated that between 0.4% to 1.8% of natural extracts (from terrestrial plans to marine animals respectively) of natural materia may contain anti-cancer principles. From 1981-2002, there has been 30 new entities for cancer that are natural products or semi-synthetic modification of natural products, based on approvals by regulatory agencies such as the US FDA(3) . Currently, over 50% of anticancer drugs approved by the US FDA are nature-derived(4) and over 60% of all drugs in clinical trials for cancers are nature related as of 2000(5). Such well-known nature derived antineoplastic agents in common oncology use include Vinblastine and Vincristine (from Catharanthus roseus), Etoposide (from Podophyllum), Paclitaxel (from Taxus brevifolia) and Topotecan (from Camptotheca acuminate). Recently, Asian natural remedies have also contributed significantly to modern anti-cancer drugs notably Camptosar (modified and derived from Chinese ornamental tree Camptotheca acuminata) and Arsenic trioxide (indirectly from Composite Indigo naturalis(6)), which have been successfully developed into modern cancer drugs. Others such as the CDK inhibitor Flavopiridol (from Rohitukine(7), a chromone alkaloid from Ochrosia leaves from India), Gossypol (from cotton seed), Artemisins (from Artemisia annua or Wormwood) are currently in clinical trials or pending further research in the West. Then there are those compounds that are in various stages of preclinical and clinical development; and many more nature derived materials such as genistein, curcumin with Asian dietary backgrounds have received widespread attention as potential chemopreventatives.

With the escalating knowledge of new molecular targets for cancer and advancing knowledge of other anticancer mechanisms other than cytotoxicity such as immuno-modulation, anti-angiogenesis and induction of cell differentiation/apoptosis, many more natural anti-cancer candidate compounds can be identified in the future. Also because of expanded prospecting for natural anti-cancer compounds from marine and other non-plant based sources as well as new drug development tools such as high-throughput screening and advances in combinatorial chemistry and genomics. Much original research has already been done in Asia where there is inherent familiarity with the native pharmacopoeia but yet there is no central resource for such material and there is limited accessibility by researchers on native studies, which may have been carried out and published, in Asian journals and in native languages. This database project intends to circumvent such limitations by providing a central repository of data and references related to Asian materia medica and potential cancer treatment, especially relating to the translation of original research either as abstract or in entirety into English to facilitate communication, reduce unnecessary replicative research efforts, and promote further investigations by the international scientific community. This project currently has the most comprehensive listing and upon completion will be the largest and most complete public database of Asian anti-cancer materia (botanical or otherwise).


Methodology & Search Strategy

In general, the AAMD is guided by an evidence based approach based on a Cochrane review structure. We collaborate with experts and academic centers in Asia to attempt first to systematically identify, and review existing paper and electronic bibliographies in English and native languages in order to identify all natural material medica which has potential anti-cancer activity. We then set to classify each material by their nature, pharmacology, and evidence of potential anti-cancer activity. Each natural material will be researched for synonymous or identical materials by Scientific as well as their native or folk names. The general nature of the material will be described along with the known pharmacology. We will concentrate on known scientific modes of anticancer activity. Evidence of potential use against cancer will be characterized as in vitro, animal and clinical reports of biological activity. Furthermore, reports of safety of the materia for human use will be represented by known toxicology and side effects.

In the first phase of our project, we will focus on Traditional Chinese (includes Korean and Japanese) Materia Medica. We systematically review and cross reference bibliographies and electronic databases by handsearch or electronically in English and native languages including nineteen reference books and thirty-six online sites for each material or herb. In Chinese alone, we routinely search more than 20 databases with nearly a half million citations (TCMLARS alone, drawing from biomedical journals published in China since 1984 has 400,100 records, whereas TCMD has approximately 20,000 records from up to 200 journals from Mainland China, Taiwan and Hong Kong) and in PubMed (National Library of Medicine, Bethesda, MD) the database includes over fourteen million citations dating back to 1957. Extracts as well as abstract common information (name, species, synonymous names, occurrence, common use in traditional medicine etc), known pharmacological information (chemistry, activity, pharmacodynamics, pharmacokinetics, toxicity etc) and evidence of anti-cancer efficacy (in vitro as well as vivo and clinical trial data). The information is then reviewed, edited and classified with appropriate references and links to original literature and subsequently uploaded to our database using the latest Quantum Art data management system. Depending on funding, we intend to produce a minimum of 30 monographs a year on selected significant materials from the database, each materia in this format:

Nomenclature: includes Scientific and Common Names (in English and Native (transliterated) languages)
Botanical
    Includes basic information about description and distribution of materia.
Pharmacology
    Includes chemical constituents, pharmacokinetics and pharmacodynamics
Efficacy
    Includes in vitro, in vivo and clinical data and ranked based on US National Cancer Institute¡¯s guideline for levels of evidence for human studies of cancer and a 2003 interim guidance for industry from the US FDA for evidence-based ranking system for scientific data.

Toxicity/Safety: includes adverse reactions, known interactions, contraindications and other precautions.

Results (Ongoing: last update 10/20)

RESULTS Although the project¡¯s intent is to eventually cover the entire Asian region (includes China, Japan, Korea, India, Mongolia, Tibet, Thailand, Indonesia and the rest of Southeast Asia), an initial survey indicates that most 90% of the Asian anti-cancer materia is found in the Chinese and related pharmacopoeia.

The database begins with a current listing of nearly 700 materia species of Sino (includes Taiwanese, Japanese, Korean, Tibetan) origin, and these in turn are (in descending order) respectively of terrestrial plant (80%), fungi (9% ),food (3.5%), insect (3%), marine (1.8%), reptile (1.2), and mineral (1%) origin.

It should be noted that the scope and diversity of materia with anticancer properties so far identified by this database is astounding especially when put into the perspective that relatively few leads were generated upon screening of tens of thousands of materia by the National Cancer Institute over a span of decades. The classification difficulties encountered in the initial identification of the each material are that there may be identical material under synonymous scientific or common names or an outright confusion of terminology used to identified the same material. Each material frequently containing multiple anti-cancer chemical components while in turn each such component may be present in various unrelated species of materia further compounds complexity. Additionally, each anti-cancer component chemical may have multiple modes of anti-cancer activities and the synergism amongst different components existing in the same materia needs further to be taken into account from an efficacy perspective. In the case of native medical systems such as Traditional Chinese Medicine (TCM), cancer treatment is undertaken within a unique theoretical framework and may involve concepts of treatment foreign to the Western oncologic approach and thus defy current scientific understanding of cancer biology. Examples of anti-cancer TCM principles of cancer treatment include: Fu Zheng Qu Xie, Huo Xue Qu Yu, Qing Re Jie Du, Ruan Jian San Jie, Yi Du Gong Du. The natural materia employed using such TCM principles may thus be difficult to screen using conventional scientific assays e.g. cytotoxicity assays, but may show relevant benefit in a clinical setting. Further complicating matters in TCM, materia medica are usually not used singly but as a cocktail or so-called formula containing multiple constituents with multiple therapeutic principles. Thus while it would be a logical step to eventually include research information and incorporate such anti-cancer formulae into our database at a future date, this is not currently the mainstay of AAMD.

1. Mukherjee AK, et al. Advances in cancer therapy with plant based natural products. Curr. Med. Chem. 2001; 8:1467-86.
2. Cragg GM, et al. Ethnobotany and drug discovery: the experience of the US National Cancer Institute. Ciba Found. Symp. 1994;185:178-90.
3. Newman DJ, Cragg GM, Snader KM. Natural products as sources of new drugs over the period 1981-2002. J. Nat. Prod. 2003:66:1022-1037.
4.Kim J, Park EJ. Cytotoxic anticancer candidates from natural resources. Curr. Med. Chem. Anti-Canc. Agents. 2002;2:485-537.
5.Cragg GM, Newman DJ. Antineoplastic agents from natural sources: achievements and future directions. Expert Opin. Investig. Drugs. 2000;9:2783-97.
6.Wang ZY. Arsenic compounds as anticancer agents. Cancer Chemother. Pharmacol. 2001;48 Suppl 1: S72-6.
7.Arguello F, et al. Flavopiridol induces apoptosis of normal lymphoid cells, causes immunosuppression, and has potent antitumor activity In vivo against human leukemia and lymphoma xenografts. Blood. 1998 ;91:2482-90.

 
¡¡
Search