In 2016 and 2017 my web master partner Dr Sanjay Chauhan and I produced educational websites for Ignyta Inc. The purpose of these websites was to recruit patients for clinical trials testing the Trk-ROS1-Alk kinase inhibitor entrectinib. The goal was not only to educate oncologists but also to appear before a competing company, Loxo, in Google searches for clinical trials.
Dr Chauhan and I would like to create more websites connecting patients and their physicians to ongoing clinical trials. We think we can produce clinical trial educational websites at competitive prices.
Unique aspects of website work
Ignyta was recruiting patients for clinical trials testing a small molecule inhibitor of Alk, Ros1 and Trk1-3 “fusion” kinases. These fusion proteins used to be call chimeras, after the myological Greek creature that is the fusion of multiple animals. Chimera, the fusion animal, really didn’t properly illustrate the concept of the protein product of a gene fusion. I created my own images. Alk, Ros1, and Trk kinases have two modules: a growth hormone binding regulatory domain and a cell signaling kinase domain that is only activated by binding of growth factors to the regulatory domain. Sometimes genes break apart and fuse to other genes. In some such cases, the kinase domain is fused to an abundant “house keeping protein.” The cell growth signaling kinase domain is constantly telling the cell to grow and divide. Let a house keeping protein be something in abundance like a field of cattle. Now imagine those cattle having the heads of tigers. Ignyta’s entrectinib, metaphorically, puts a muzzle on the cancer driving tiger.
NTRK Fusions was our first site. The role of Trk kinases in cell signaling was described on a page on this site. Kinases relay messages from growth factors to the nuclei of our cells. Kinases transfer the γ-phosphate of ATP to tyrosine, serine, or threonine amino acid side chains of inactive enzymes, thus activating them. Often these enzymes are kinases themselves.
Interestingly, the neurotrophic tropomyosin related kinase 1 NTRK1 gene discovery resulted from sequencing of a colon carcinoma. Tropomyosin 3 is an actin binding house keeping protein.
MASC tumors soon followed. It seemed like I reviewed every account of Mammary Analog of Secretory Carcinoma (of the breast) and other tissues. In addition to the histology, we were very focused on protein biomarkers of MASC. Ingyta has an interest in companion diagnostics. There was some short term interest of trying to publish my hypothetical MASC feed forward loop. Trying to prove such a thing is a bit more difficult.
Acinic Cell Carcinoma was a follow up to MASC tumors. Often salivary tumors diagnosed as acinic cell carcinoma are reclassified as MASC. The focus of this site quickly expanded to other salivary tumors that have been reclassified as MASC. It was quite a challenge, and a lot of fun, to analyze gene rearrangements in related salivary tumors.
Trk mutations was a really challenging site to create. Ignyta might have been exploring whether entrectinib would be indicated when normal, wild type, TrkA (the protein) is over expressed. What other cancer driving proteins might be over expressed when the protein TrkA is over expressed? A goal was to establish the difference, in my own mind, between gene product over expression and gene amplification. Perhaps oncologists were a bit rusty on these concepts too. We were given the title of our pages based on what our SEO experts told us. I turned “gene rearrangements” into a page on “mRNA splicing variations” in cancer. Trk fusions covered different types of gene fusions, fragile sites, and why there may be so many NTRK1 gene fusions within this gene fusion hot spot.
Secretory Cancer was one of our last sites. This site discusses the four tissues in which the ETV6:NTRK3 gene fusion drives secretory cancers. This site contains the history of the original discovery of the ETV6:NTRK3 gene rearrangement in a fiborsarcoma and later discoveries in epithelial cell carcinomas. Case studies are also presented. The take home message is that even if the secretory cancer has been successfully treated by traditional means, get tested in case it comes back.
Ros1 Tumors was a site written for both lay audiences as well as PhD scientists and physicians. Most of the other sites were produced so that it appeared that we were not trying to directly advertise to patients. I wanted to create a site that would appeal to an oncologist and the patient for whom the oncologist had found a clinical trial.
A once in a life time experience
Dr Chauhan and I knew that Ignyta was competing with Loxo for patients in their Trk inhibitor, Loxo 101, clinical trials. We were unaware of a pending deal between Loxo and Bayer. We were also unaware of the Roche purchase of Ignyta for 1.7 billion US dollars until after it happened in late 2017. We would like to think our websites might have helped Ignyta a little. Our efforts helped Ignyta appear before Loxo in Google searches for Trk inhibitor clinical trials. We received notification when we needed to incorporate other terms in our websites to beat Loxo in Google searches for rare cancers that may be treated by these targeted Trk inhibitors. When Loxo realized what our websites were doing, they started creating some of their own that were beautiful and slick but not as informative and heavy on the SEO.