A tale I love telling. For several reasons. A potential method for treating cancer. And, the development was effected by chemical engineers.
Drs. H. Jayatilaka, D. Wirtz, P. Tyle, J. Hu, H.J. Kim, J.S.H. Lee, P-H. Wu, D.M. Gilkes (all from Johns Hopkins) and J.J. Chen, M. Kwak, and R. Fan (all from Yale) comprise the team that reported these interesting results. Jayatilaka was the first to make the observation under the tutelage of Dr. Wirtz.
What did she notice? Cancerous cells, when they became “too” densely packed, break away and spread their havoc. That’s vastly different than our previous concept (actually an hypothesis)- that metastasis was tumor-size dependent, not really related to tumor density. In particular, we postulated that the growth of tumors and cell spreading were separate activities. (That’s exactly what these cells do in vitro [in petri dishes, not in real situations].
Moreover, this team has identified the actual biochemical signal involved in turning on the metastasis process. Which is key- since the bulk of deaths from cancer (on the order of 90%) arise due to metastasis- the spreading of cancer cells from one region of the body to (many?) other(s).
Perhaps more importantly than identifying the biochemical signal- the team has determined that two existing drugs are able to attenuate the signal, to slow down the metastatic process. Once the tumor attains “metastasis density”, it releases interleukin-6 (il-6) and interleukin-8 (il-8), two proteins. These notify the cancerous cells (via WASF3 and Arp2/3) that it’s too crowded and the cells must break for greener (and deadlier) pastures. As further indication, if these proteins are sensed by cancer cells that have NOT attained the “metastatic density”, they still begin to metastasize.
Th animal model (using 3D matrices) they developed demonstrated the ability of cells to create pseudopods (protrusions into the environment) and those dendritic protrusions increased as tumor cells proliferated- but plateaued once a specific cell density was achieved.
Up to now, most of our therapeutic treatments had been aimed at killing cancer cells- not how they spread (metastasize). That explains why the goal of current therapy is to shrink the primary tumor size. This research is going to lead to an entirely new approach, as reported in a recent (26 May 2016) issue of Nature communications. (The article title is Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration.)
The two drugs in concert that provide this control are Tocilizumab (normally used for rheumatoid arthritis) and Reparixin (currently used for cancer treatment). When provided for use against the cancer mass, the drugs bind to the interleukin receptors- which means the signals are blocked and the instruction to metastasize is attenuated.
Of course, this is still a preliminary finding. The goal is to hone the two drugs’ actions to ensure they terminate the metastasis, not just attenuate it. And, the task is now to discern how well the two drugs perform in human trials, because only animal models have been used to date.
The team also expects that the cocktail would be enhanced for human use- where a chemotherapeutic agent would be employed to shrink the primary tumor, along with these drugs that attenuate the metastatic signals.
I hope have great additional results to report soon.
Next month will be the 2nd anniversary of my childhood best friend’s passing after a nearly four year struggle with cancer. Thank you to all the scientists working on a cure. We can only hope…….
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We’ve been having a war on cancer since Nixon was president. That- the war on drugs and the war on poverty are the only wars that exceed the length of OUR involvement in Afghanistan.
Excited by the preliminary findings – it would be nice to have a breakthrough in cancer treatments, will be interested to follow the human trials.
I like the fact that this will both stop metastasis- and afford us the ability to treat the underlying tumor, Megan.
It is quite interesting, Roy!
Cancer cells are not acting the same way as all other cells, however,
they are brilliants! Thanks for sharing!
Yes, most other cells don’t metastasize. Which is also because cancer cells are less specialized than other cells in our body.
Thanks for the visit and comment, Gaetane.