I have written
a lot that personalized medicine in oncology is ineffective and unproductive. It is not funny any more to write about it, however I think I have to because I have found
one very rational summary of the situation.
Some very important statements and conclusions:
Ever since the genomics revolution began in the 1990s and accelerated in the 2000s, the dream has been to use the gene expression profiling information and the genome sequences of individual cancers derived from next generation sequencing technology and the latest analytic techniques. It seemed like a perfectly reasonable dream early in the genomics revolution, so much so that the Cancer Genome Project, which has been sequencing cancer genomes furiously, seemed like the right way to lay the groundwork for personalized cancer therapy. ...
If there’s a place where evolution will inform medicine at least as much as it does in infectious disease and the development of antibiotic resistance in microorganisms, it’s in cancer. The knowledge that tumors are heterogeneous and that they undergo evolution based on the selective pressures from the host, including characteristics of the organ and its microenvironment and other factors, is not new. Neither is the knowledge that cancer cells undergo evolution under the selection pressure of various therapies, thus developing resistance to those therapies. Indeed, it is the tumors that are less heterogeneous because they are driven by a single mutation, that tend to be actually curable or best controlled with single-agent targeted therapies. Just like the case in whole organisms undergoing evolution in response to selective pressures, genetic variability in cancer cells provides the raw material upon which evolutionary selection pressures can operate. The result is that tumors with more genetic heterogeneity tend to develop resistance to therapy sooner....
So what the new genomic analytical techniques have re-emphasized to us in a quantitative manner that we couldn’t use before is that not only is cancer not a single disease but that cancer types are not single diseases. Breast cancers, for instance, have been shown to harbor at least 1,700 different mutations, but only three of them showed up in at least 10% of patients, with the great majority of them being unique to each patient.
Not only that, but each TNBC is in essence several diseases, because each TNBC is made up of many different clones that have evolved as the tumor itself grew, progressed, and evolved. All of this occurs even before the tumor has been subjected to any treatment at all. As if that’s not bad enough, it would appear that tumors are a mosaic of groups of many different tumor cell types that develop through branching evolution such that metastases can be very different from the primary tumor and even different regions of the primary tumor can be very different from each other, so much so that finding a “favorable prognosis signature” on a core biopsy means only that that one area biopsied has that gene signature. Large areas elsewhere in the tumor could have the unfavorable prognosis signature....
It is, however, becoming clear that developing personalized therapies for cancer is going to be a lot more difficult than we had thought before. I asked the rhetorical question, “Why haven’t we cured cancer yet?” The answer is, of course, that curing a single cancer, much less many cancers, is really, really hard. Scientists not only have to contend with basically a continuous spectrum of mutations between individual cancers that renders the concept of even single cancer subtypes horribly naive, but with a near continuous spectrum of mutations between groups of cells in a single tumor...
Let us be honest. For materialists and scientists it is obvious that personalized medicine approach to the cancer treatment is dead. What is the cause of the death? Ontology, the objective reality, the nature and it's laws. Personalized medicine is based on oversimplified mechanistic theory which is absolutely incorrect. But by stating that we do not propose any substitute, any novel approach for coming paradigm. In order to make any rational work in the area we have to have some plan, some scenario, some ideas... And here we have vacuum, death-black vacuum... We have spent all the resources into genomics and other hype-research and now we are poor conceptually and methodologically. What we need is not just to find another gene or target or protein involved in the cancer development – it is too simple, too mechanistic, too meaningless. We need complete paradigm shift, really revolutionary, which introduces completely new approaches into life-science field. Who will do it – another story, but I know that it is doable...
Former candidates:
