Thursday, January 24, 2008

"Natural" Cancer Therapy

The last edition of the Cancer Research Blog Carnival saw a submission with a link to an anti-chemotherapy site urging patients to seek out 'natural' alternatives to chemotherapeutics (no mention of what these natural alternatives might be). My first thought was 'what about taxol?' - a compound derived from the bark of the yew tree commonly used to treat a variety of cancers. A lot of the push for 'alternative medicine' is based on a fear of traditional medicine - that is, man-made chemical treatment. Personally, I think these fears are largely unfounded and ignore the history of many pharmaceuticals in use. Here are some natural products currently in use in the cancer clinic. Someone preaching natural cures over tested medicine probably doesn't know what they're talking about.

Taxanes - Taxanes are plant alkaloids that interfere with spindle fibres during mitosis. As already mentioned paclitaxel (taxol, pictured) is a chemotherapy agent derived from the Pacific yew tree (Taxus brevifolia). The drug is approved for use in treating many cancers including ovarian, breast and lung. Originally discovered in 1960s as part of a plant screening operation, the Pacific yew was virtually the only source of taxol until 1993 when alternative sources were sought for ecological reasons - in 1969 it took over a metric tonne of bark to produce 10g of paclitaxel. Now the drug is produced by a plant cell fermentation method.

Vinca alkaloids - In a different class of plant alkaloids from taxanes are the vinca alkaloids, with vincristine (pictured) being a typical example. These compounds are used as intravenous chemotherapeutics primarily in the treatment of lymphoma and, similar to taxanes, are mitotic inhibitors. Vincristine is derived from the leaves of the Madagascar periwinkle, Catharanthus roseus (also the source of the chemo drug vinblastine), and was approved as a cancer drug in 1963. However, the leaves of this plant had been used for ages as a folk remedy which is how the initial discovery was made and is a fine example of how 'alternative medicine', once tested, ceases to be alternative and becomes mainstream medicine. (This is not to say that all folk remedies have some underlying efficacy).

Topoisomerase Inhibitors - One method of killing rapidly dividing cancer cells is inhibiting topoisomerase. Topoisomerase I inhibitors include camptothecins (pictured) which are plant compounds derived from Camptotheca acuminata (Happy Tree), discovered in a systematic plant screen. Topoisomerase II inhibitors include etoposide, which is derived from the American Mayapple. Both are used as part of a chemotherapeutic strategy.

Anthracyclines - Anthracyclines are a class of drug that include epirubicin, daunorubicin and doxorubicin (pictured) which act as DNA damaging agents, inducing strand breaks by inhibiting topoisomerase II or causing oxygen free radical damage. They can also intercalate with DNA and prevents DNA and RNA synthesis. These drugs are commonly used in chemotherapy and find their origins in soil microbes. Daunorubicin and the related doxorubicin (and some related compounds) date back to to the 50s when they were isolated from the bacteria Streptomyces peucetius and shown to be effective against mouse tumours. Incidentally, the bacterial genus Streptomyces also produces a large number of clinically useful antibiotics (such as puromycin, chloramphenicol and streptomycin) and the anti-metastatic migrastatin.

Antitumour antibiotics - One of the antibiotics produced by Streptomyces is bleomycin (pictured) which gained FDA approval as a chemotherapeutic in 1973. This bacterially produced glycopeptide is used to treat testicular cancer and Hodgkin's lymphoma, among others, and works similarly to anthracyclines, generating oxidative damage and DNA strand breaks.

Of course, this is not a comprehensive list - there are other molecules found in nature that are used in cancer treatment. Some are based on natural compounds, but modified to be more effective. Others rely on modern synthesis rather than extraction from the source organism. One thing in common between the naturally derived drugs above and 'unnatural' modes of therapy is that all of them have been tested and shown to have some efficacy. Don't accept less from your treatment.


Rob said...

I totally agree with the obvious point of the post, that many pharmaceutical agents are inspired or directly derived from naturally occurring biologically active compounds. However this post also points out the reductionism involved in the development of medicines. A plant that is determined to have beneficial effects is reduced to a single molecule. I recently heard on the Scientific American podcast about an ethnobiologist/bioprospector that takes indigenous knowledge of medicinal plants and tries to make use of ALL the knowledge. Instead of just what plants he takes into account how they are prepared, when they are harvested and in what environments the best plants are. He also doesn't discount that there may be more than one biologically active compound in a single plant. Of course, when all is said and done the compound/compounds could be mass produced as drugs. Pretty interesting. I digress. good post.

Bayman said...

Nice post and comment. Following up on Rob's comment, one consequence of using more "natural" less reduced extract from plants as in indigenous approaches the potential for naturally occurring combinations of molecules that might synergize in useful ways. Interestingly this is also now of the the main ways that cancer researchers are working to improve the activity of the purified chemotherapeutics currently in combination therapy. Maybe we are in the process of developing our own complex medicinal concoctions like those of older cultures...but from more defined and basic starting materials.

Doctor David said...

I actually give this speech to patients and their families on a regular basis. I think too few people realize how many pharmaceuticals are natural products.

But there's an important flip side, too. Just because a drug is "natural" does not mean it's safe. Hemlock and Belladonna come to mind right away. These are a bit too "fantasy novel" for most people, though, so I talk about poison mushrooms. Anyone who, as a child, played in the woods, was told at one point about the dangers of eating wild mushrooms, because some are edible and some are deadly. Interestingly, all are "natural products".

The Doc said...

Doctor David has hit on something quite important. "Natural" is developing a new meaning in modern English - it now means "safe" as well as "not derived from human".

If it's 'natural' it can't be bad for you, like lions, tigers, bears, and poison ivy.

One of the groups I came from back in New Zealand had a long history of locating and identifying bioactive components from sea sponges - including some anti-cancer drugs. Infact I spent an honors year trying to recreate two of them synthetically: coproverdine, and 9-methoxystrobilurin K.
I believe Coproverdine is a possible anticancer agent.

Doctor David said...

At the risk of "tooting my own horn", I posted something back in July about the effect of Trabectedin on myxoid liposarcoma. Trabectidin is derived from sea squirts... does that make it a "natural medicine"?

It's sad that the English language is morphing in such a deceptive way, as The Doc points out. Poison Ivy is natural. So is the spirochete that gave me Lyme disease last fall... but that cost me 3 days in the cardiac ICU, so I'm not so sure that in that case "natural" meant "safe" at all!

Kamel said...

Lots of good points being made here. I hope I didn't imply that natural products are safe by definition - the mushroom example has come up frequently on this blog, particularly in some 'quack of the week' discussions.

I guess I was taking the point of view that 'natural medicine' has, at least in some cases, become analagous to 'alternative medicine' and really that's not the case. There are plenty of 'natural medicines' that falls squarely in the realm of evidence-based medicine. Really though, the source (natural vs. artificial, etc.) shouldn't be the criteria for evaluating a therapy - the concern should be whether it's been tested and works.

"Natural" does not mean "safe" and "Allopathic" or "conventional" medicine does not necessarily mean "unnatural".

But as The Doc points out, deceptive/ambiguous language is a tool of quacks and pseudoscientists.

Bayman said...

Interesting points. I can't help but to tie it back to our recent discussion on cloning, because I think the same phenomenon is at work here.

I think in these types of cases the concept of "naturalness" or "unnaturalness" provokes a strong instinctive response that causes people to take leave of reason in evaluating foods or drugs. I would guess this is a strong instinct that nearly all organisms share, a hard-wired instinct to prefer the familiar over the novel when it comes to putting things into our bodies. It is easy to see why this instinct is important - what we put in our bodies is a matter of life or death. However it's important to realize humans have another tool that we can use to make these types of decisions - reason - and the property of "naturalness" has no place in this process.

Dr CL Smith said...

I wish to thank all contributors to this discussion because I too am in the position of answering patients queries about natural v.s pharmaceutical. I can print this for clients to read as most of the important points have been covered.

One thing I would add is that clients are often scared and desperate for any way to escape the difficult treatments that a cancer diagnosis can represent to them. As an alternative Practitioner (former Univ. Professor in Med.) I use alternative med mainly herbs and fungus along with their modern medical care. Even though I recommend "evidenced based" alternative therapies that work with the chemotheropeutic treatments. The same clients who sought me out, will bring to me many, many web sites for products that they want to try. They keep looking for a quick and easy cure instead of what I may have added that is having a positive effect. The herbs or compounds that have effect are more laborious to use than what they wished for at the beginning of their search for alternatives. I have come to realize that many people go through the same stages of grieving as they would for a death. Looking for treatments that are miraculous and safe and gentle can be part of the denial stage. I would simply add to treat all patients and family with kindness and give them time.
Alternative Dr.

buy cialis said...

buy cialis