The immune checkpoint blocker pembrolizumab (Keytruda, Merck) has proven most successful to treat solid tumors harboring a DNA mismatch repair (MMR) deficiency. This striking result recently reported by Luis Diaz Jr., Bert Vogelstein and their collaborators was anticipated a couple of years before by Dr. Vogelstein, a towering figure in oncological research. Ariel Fernandez has now shown that it is possible to generate a drug-promoted phenotype mimicking the MMR deficiency in solid tumors and thereby engineer a generic hypersusceptibility to Keytruda. This sensitivity is achieved through drug-induced metabolic stress on DNA synthesis.
The striking results by Diaz, Vogelstein and coworkers prompted Ariel Fernandez to address the following question: Is it possible to induce the MMR deficiency in any solid tumor, for example through targeted drug-based therapy, and thereby enhance the cancer antigenic activity and diversity to turn the Keytruda-drug combination into a universal cure for cancer?
As work at Ariel Fernandez Consultancy reveals, the answer to this question is a resounding yes. The key to the problem resides in identifying a signaling pathway that gets recruited to promote MMR and then identifying a kinase inhibitor that would block that pathway. The MMR deficiency-inducing kinase inhibitor has been found at Ariel Fernandez Consultancy. The potential of such drug-Keytruda combinations as universal treatments for solid tumors deserves clinical evaluation. Collaborative work is underway at Ariel Fernandez Consultancy to validate this paradigm. This may well be a decisive step in cancer cure.
Related Reading
Ariel Fernandez: “Engineering Tumor Hypersusceptibility to Checkpoint Immunotherapy”, Trends in Cancer (2017) Published online September 4.
Science Transparency 
Amazing stuff. So, Fernandez is saying we could induce the Lynch condition through drug treatment and this will make the patient susceptible to Keytruda? We know already that the patient with Lynch condition can be cured with Keytruda, from the work of Vogelstein et al.
This is great. Needs clinical evaluation NOW!
However, once some DNA damage is induced we need to stop, after immune system took the bait.
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It seems that is what Dr. Fernandez is claiming. The targeted therapy would probably need serious fine tuning, though.
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