cancer cells escape blood vessels

IHSIHS, Nice. The "Drugs that interferes with actin prevented the spread of CTC in mice", I put that phrase into google. Came up with this from Wiki. Lets see if it'll copy. Nope, it didn't copy the whole thing. https://en.wikipedia.org/wiki/Cytoskeletal_drugs

It'll be exciting to see what kind of research will occur with Cholchicine. It's used for the acute gout. We'll tolerated and inexpensive. Could see it being given before and after biopsy and surgery to reduce the risk of CTC's release or circulating at the time of surgery. COOL.

There are three drugs already used for Chemo on the list. Since this is new info on drug action. It would be interesting how the connection of these three drugs were made to cancer therapy. Trial and Error? Were all the other drugs tested? Are they now being tested?

Wiki: Cytoskeletal drugs are small molecules that interact with actin or tubulin. These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol which stabilized microtubules or Phalloidin which stabilizes actin filaments. Others such as Cytochalasin D bind to actin monomers and prevent them from polymerizing into filaments. Drugs such as demecolcine act by enhancing the depolymerisation of already formed filaments. Some of these drugs have multiple effects on the cytoskeleton, for example Latrunculin both prevents actin polymerization as well as enhancing its rate of depolyermisation. Typically the microtubule targeting drugs can be found in the clinic where they are used therapeutically in the treatment of some forms of cancer.^[1] As a result of the lack of specificity for specific type of actin (ie cannot distinguish between cardiac, smooth muscle, muscle and cytoskeletal forms of actin) the use of these drugs in animals results in unacceptable off target effects. Despite this the actin targeting compounds are still useful tools that can be used on a cellular level to help further our understanding of how this complex part of the cells internal machinery operates. For example, Phalloidin which has been conjugated with a fluorescent probe can be used for visualizing the filamentous actin in fixed samples.

Drug Name	Target cytoskeletal component	Effect	Clinical applications
Colchicine[2]	microtubules	prevents polymerization	Used to treat gout
Cytochalasins[3]	actin	prevents polymerization	none
Demecolcine[4]	microtubules	depolymerizes	chemotherapy
Latrunculin[5]	actin	prevent polymerization, enhance depolymerisation	none
Jasplakinolide[6][7]	actin	enhances polymerization	none
Nocodazole[8]	microtubules	prevents polymerization	none
Paclitaxel (taxol)[9]	microtubules	stabilizes microtubules and therefore prevents mitosis	chemotherarpy
Phalloidin[10]	actin	stabilizes filaments	none
Swinholide[11]	actin	sequesters actin dimers	none
Vinblastine[1]	microtubules	prevents polymerization	chemotherapy Cytoskeletal drugs are small molecules that interact with actin or tubulin. These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol which stabilized microtubules or Phalloidin which stabilizes actin filaments. Others such as Cytochalasin D bind to actin monomers and prevent them from polymerizing into filaments. Drugs such as demecolcine act by enhancing the depolymerisation of already formed filaments. Some of these drugs have multiple effects on the cytoskeleton, for example Latrunculin both prevents actin polymerization as well as enhancing its rate of depolyermisation. Typically the microtubule targeting drugs can be found in the clinic where they are used therapeutically in the treatment of some forms of cancer.[1] As a result of the lack of specificity for specific type of actin (ie cannot distinguish between cardiac, smooth muscle, muscle and cytoskeletal forms of actin) the use of these drugs in animals results in unacceptable off target effects. Despite this the actin targeting compounds are still useful tools that can be used on a cellular level to help further our understanding of how this complex part of the cells internal machinery operates. For example, Phalloidin which has been conjugated with a fluorescent probe can be used for visualizing the filamentous actin in fixed samples. A cancer cell that was fixed and stained with phalloidin to visualize the actin cytoskeleton.Drug NameTarget cytoskeletal componentEffectClinical applicationsColchicine[2]microtubulesprevents polymerizationUsed to treat goutCytochalasins[3]actinprevents polymerizationnoneDemecolcine[4]microtubulesdepolymerizeschemotherapyLatrunculin[5]actinprevent polymerization, enhance depolymerisationnoneJasplakinolide[6][7]actinenhances polymerizationnoneNocodazole[8]microtubulesprevents polymerizationnonePaclitaxel (taxol)[9]microtubulesstabilizes microtubules and therefore prevents mitosischemotherarpyPhalloidin[10]actinstabilizes filamentsnoneSwinholide[11]actinsequesters actin dimersnoneVinblastine[1]microtubulesprevents polymerizationchemotherapy

Tried a couple of ways to C&P the Wiki Cytoskeleton info. It didn't work, but the link is in the above post.

I have a question that I'm not able to easily find the answer to on Dr. Google. Does a "normal healthy" patient without ever having had cancer have zero circulating tumor cells?

I've never had a CTC test, only CEA and CA 27-29, which were both well within the normal healthy person range. Should I ask for a CTC test?

I have a friend that's in a trial at MDMAnderson. Part of the bloodwork was measuring the CTC's before during and after completing the protocol of the trial. Happily they decreased to either not detectable or very low. Sorry, forget what she told me. She's TNBC. Not sure how often they plan to run them. Would seem at this point since they have a running profile that the CTC level could be used as a tumor marker.

This is a good article. It's from 2013, so not the latest, but gives a good overview.

"In order to enter the circulatory system, breast cancer cells must undergo extensive cytoskeletal alterations. The EMT program has been widely studied as a mechanism that enhances cancer cell motility and escape from the primary tumor, but recent studies using developing technology to isolate CTCs suggest that the EMT program provides additional advantages to cancer cells in the very different microenvironment of the circulatory system. The EMT program can be particularly advantageous for breast CTCs since it appears to increase invasiveness to aid in the generation of CTCs, confers resistance to anoikis once the cells are in circulation, and promotes McTN (microtentacles) formation and CSC character, giving the CTCs a metastatic advantage in exiting the bloodstream and surviving to emerge later as dangerous metastatic lesions."

http://www.mdpi.com/2072-6694/5/4/1545/htm