Sunday, July 1, 2007

Medicine from the Sea

The internet has been positively buzzing with articles about a new cancer drug called Trabectedin (also known as ET-743) and its activity against a subtype of soft tissue sarcomas – myxoid liposarcoma. There have been articles on the BBC web site, in science blogs, and even on yachting websites. What’s all the fuss about? Well, there are two exciting things: first, there are precious few drugs that have any activity against soft tissue sarcomas, so the discovery of any new effective treatment is cause for excitement. Second, and possibly even more interesting, is that the drug is effective against just this single subtype of soft tissue sarcomas.

Why is this exciting? Well, the identification of a new chemotherapy drug for soft tissue sarcomas is a big deal. Granted, soft tissue sarcomas are not the public health menace that other cancers might be. But the number of drugs that are useful in the treatment of this type of cancer is very small indeed. The mainstay of treatment for soft tissue sarcomas remains surgery and radiation therapy, but these are local treatments, meaning that if the sarcoma has spread, these treatments have limited usefulness. Sarcomas that have spread have to be treated with chemotherapy, and the two most active drugs, doxorubicin and ifosfamide, have potentially devastating side effects, including heart failure, kidney dysfunction, and secondary leukemia. The results with trabectedin are brand new, and no one yet knows how to best integrate this drug into a treatment regimen, but with every new drug comes the promise of effective treatment without long term side effects.

The second big deal, which I suppose may be more exciting to us cancer doctors than to patients, is the selective effect of this drug on myxoid liposarcoma. Previously, the field of sarcoma treatment has been dominated by what I believe is an outmoded way of thinking – all sarcomas are the same. Clearly, this is not true, as the treatments for Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma (the most common types of sarcoma to affect children) are all different. Despite that, all other sarcomas are essentially treated the same, no matter what the diagnosis, no matter what they look like under the microscope. The finding that trabectedin is effective against a single type of sarcoma strengthens the idea that not all sarcomas are the same, that “histology matters” as we docs like to say, and that knowing precisely what kind of sarcoma you have will one day ensure that you get just the right treatment for your diagnosis.

Another really cool part of this finding is the source of this drug – the lowly sea squirt. What’s a sea squirt? Well, prior to these reports, I had no idea. Being the inquisitive sort, I looked it up. Apparently, a sea squirt is quite the interesting beast. The larva of the sea squirt is mobile and has a backbone, along with a brain, a balancing organ, and an eye. The larva swims around, finds a suitable place to land, and attaches itself, never to move again.











The adult has a spherical or cylindrical body attached to its substrate by a stalk. A siphon of sorts brings water into and out of its “pharyngeal chamber”, and feeding depends on the formation of a mucus net that traps plankton. The adult form has no backbone, no brain, no eye, and no balancing organ. It is, however, quite beautiful.



So… is this something unique in cancer therapy? Well, yes and no. Yes, in the sense that this is the first sarcoma-directed drug to be developed from a marine organism, but … this is NOT the first “natural” chemotherapy drug. Vincristine holds that title. Vincristine is derived from the leaves of the vinca, or periwinkle, plant. Periwinkles may even grow in your very own garden. I know my mother loves to grow them… they’re easy to care for and make pretty flowers. So it seems that the past and the future of chemotherapy will owe a huge debt to Mother Nature. More on this in future posts, I’m sure.

4 comments:

Lisa said...

Thanks for sharing as a liposarcoma patient and a doctor I find this so fascinating I had to blog about it too.

Thanks

Dan G said...

Doctor Dave, this is a very
interesting post and gives us hope for cures that are less damaging to the rest of the body than doxorubicin and ifosfamide:

Do you know if anyone is looking into whether Trabectedin can be used in parallel with doxorubicin and ifosfamide, or some combination of the three in differing ratios?

Could Trabectedin be used for patients that have had myxoid liposarcomas removed using dox./ifos./surgery, to keep the tumor from recuring, as a maintenance drug?

Dan G.

matt said...

Hopefully this will be effective against rhabdomyosarcoma, as well as liposarcoma. I hope that it will not produce the severe bladder side effects that ifosfamide produces.

cialis professional said...

Thank you! I didn't know they picked up on it until I saw your comment.