Taken from Science and Knowledge n. 37.
Professor Pier Mario Biava, an occupational physician, has been studying the relationship between cancer and cell differentiation for several years: he has isolated the differentiation factors of stem cells capable of inhibiting or slowing the growth of various types of human tumors. Lecturer for many years at the Graduate School of Occupational Medicine in Trieste, he currently works at the IRCCS Multimedica in Milan.
He is president of the Foundation for the Research of Biological Cancer Therapies and vice president of the International Academy of Tumor Marker Oncology. Over the past two years he has actively participated in the advancement of research in the field of the relationship between stem cells and cancer. Lately he was able to curate as guest editor the special issue of an important international medical journal, Current Pharmaceutical Biotechnology (volume 12, n. 2, February 2011, available in Current Pharmaceutical Biotechnology, on the topic “Reprogramming of Normal and Cancer Stem Cells “(Reprogramming of normal and cancerous stem cells).
Let’s take up and deepen the theme already addressed in issue 26 of the magazine, interviewing Professor Biava on the latest developments in his interesting and promising research on cancer therapies.
At the current stage of research, in your opinion, what is the role of cancer stem cells in determining the malignancy of the cancerous disease?
Numerous researches carried out all over the world have shown that at the base of the malignancy of tumors there are cancer stem cells, resistant to chemotherapy and radiotherapy, which are able to metastasize and reproduce, starting from a few cells, the whole tumor. Within a neoplasm there may be different cell clones: usually when a tumor, perhaps after responding to traditional therapies of consolidated efficacy and therefore reducing in its size, does not heal, relapses and metastasizes because it contains cancer stem cells: against they have not yet been found truly effective therapies.
The philosopher of science Ervin Laszlo in the preface to his book Cancer and the search for lost meaning (published by Springer, 2008) states that it is one of the most extraordinary texts he has ever read. This statement starts from the fact that, for Laszlo, the exceptional discovery she made is in having identified the growth power of cancer in an intercellular communication defect. Restoring a healthy flow of information between cells and the consequent reprogramming of cancer cells within a normal physiology is the way to go for restoring the health of the organism. Do we know something more specific about this healing process today?
Fortunately, today all the most advanced research in the world shares the idea that the malignancy of tumors is linked to the presence of altered stem cells. This is the first important step that can lead us towards new and different therapeutic approaches compared to those adopted so far. Furthermore, all researchers today know that normal stem cells can be reprogrammed and the concept is emerging that cancer stem cells can also be reprogrammed and differentiated in some way. The idea that cancer stem cells could be at the base of the malignancy of tumors and that these could be reprogrammed is the way I have been following for about 20 years: this is why the scientific journal Current Pharmaceutical Biotechnology asked me to be Guest Editor of a number special with the title “Reprogramming of Normal and Cancer Stem Cells”. This is a theme that, in other words, can be declined following the concepts used by Laszlo: as a great philosopher of science Laszlo expresses the concept of reprogramming as correct information: if you provide cancer stem cells with correct information, they can be addressed towards normality, thus restoring the health of the organism.
What are the biggest difficulties in proposing a therapy of this type? Both from a bureaucratic point of view and from a medical point of view?
The greatest difficulties from the therapeutic point of view are represented by the fact that tumor diseases are different diseases, even if they share, at the base, common pathogenetic mechanisms. In fact, every type of tumor, if we place ourselves in the context of a reprogramming therapy, should be treated with targeted interventions, practically made to measure for the patient. Furthermore, it must be taken into account that in a non-destructive, but “re-educational” approach to the cancer cell, the instructions to be given to the cell to “convince” it to take the path of normal physiology are complex, that is, it is necessary to administer a network of substances and not single molecules In fact, cancer stem cells are cells that have partially or totally lost the program of cellular differentiation and to bring them back to normal, they must be given the missing part of the program. Hence the use of stem cell differentiation factors as a new therapeutic approach. In order to arrive at an effective treatment, in addition to a better understanding of the alterations that are present in each individual tumor, it is necessary to review the legislation of the drug, which the Ministries of Health of the various countries adopt: it is necessary to adapt this legislation to the new visions that arise in biology. they are leading the way. This revision is essential not only to start a new therapeutic path against cancer, but also to address the new regenerative therapies in the field of degenerative diseases and transplants.
For which types of cancer is it possible today to provide information to cancer cells so that they pass from a state of multiplication to a differentiation process, reintegrating themselves correctly into the normal dynamics of the human body?
At present, research on the reprogramming of cancer stem cells is carried out experimentally in the laboratory. There are numerous research centers in the world that are taking an interest in the subject and it is possible to hope that in a future, however, still quite distant, good results can be obtained (in our research laboratories, the lines of human tumors that have responded in vitro, slowing their growth, are the following: gliobastoma multiforme, an aggressive brain tumor, breast, liver, kidney, colon cancer, melanoma and acute lymphoblastic leukemia). As for the clinical approach, I have developed a first natural product that uses stem cell differentiation factors to control tumor growth. It is a product where the differentiation factors are contained in a very low dose and which is used to improve the performace status and the quality of life for cancer patients in advanced stages. This product has given good results in the treatment of primary liver cancer, where, in a controlled and randomized clinical study on 179 patients, the improvement in performance status has affected over 80% of patients and regressions and stabilizations of the disease. Today, this therapy should only be used in intermediate-advanced stage hepatocellular carcinoma, taking into account the above, namely that each type of tumor requires specific treatment, which may be suitable for some, but not for others.
Do we have any statistical quantifications of the results that can be obtained with this revolution in cancer cell information?
In intermediate-advanced hepatocarcinoma (primary liver cancer) we had 20% regressions and 16% stabilization of the disease with a significant increase in the survival of all patients who responded to treatment: from a poor prognosis of 8-10 months, a survival of over 5 years was passed for 65% of patients.
Going into the merits of the therapy, what kind of protocol is prepared? Are natural remedies or synthetic drugs used? Does diet play a role? Or does everything change with respect to the standard physiological view?
The protocol – which involves the use of natural products – is very simple: it involves taking 40 drops 3 times a day of a solution of these differentiating factors, keeping them in the mouth under the tongue for 1 minute. The treatment has no negative side effects and, if after three months there is a progression of the disease, it can be stopped (if after three months it has not worked, it means that for that specific patient the treatment is not effective). Obviously, diet is very important as an element of support for treatment. In summary, we can say this: it is necessary to eliminate from the diet foods containing animal fats, red meats, dairy products and cheeses, and instead adopt a diet low in fat, rich in fiber and therefore in vegetables and fruit. Among the meats it is necessary to choose those of fish, chicken, rabbit, turkey, or white meats.
What can we expect in the near future from stem cell research and organic communication mechanisms? The pioneering work of Professor John Klavins, former president of the International Academy of Tumor Marker Oncology, which laid the foundations for a new scientific paradigm, will finally become a shared heritage of the medical community and a source of new impetus for anti-cancer research not spoiled by the context. where did it arise?
I think things are changing rapidly. Even at the level of basic research, we are realizing that the reductionist approach, based on the study of punctual mechanisms, is no longer sufficient: it is important, but it does not make us understand the complexity of life. Today, experimental research is realizing that biological responses depend on the context, that is, on the networks of relationships and on the micro-environment in which the cells are found. The communication between cells changes radically in different contexts and is sometimes completely interrupted: this is what happens in tumor diseases, where a subsystem of cells has lost contact with all the others and is organized as a new complex adaptive system that develops using a message meaning code different from that of adult cells. It is an embryonic code of signification, whose underlying meaningful message is: to organize a new life. And the tumor organizes its own life, but to the detriment of the adult organism. Only contact with “his” embryonic micro-environment can lead the new adaptive system represented by cancer to correctly re-signify messages and normalize communication with adult cells. Today many researchers are realizing this and direct their research to the studies of contexts and relationships to create complex interventions: many publications today study gene networks and substance networks to establish which relationships exist in different contexts. networks of genes and networks of regulatory substances. This bodes well for the future.
We interviewed Pier Mario Biava
Occupational doctor, he graduated in Medicine at the University of Pavia in 1969, specializing first in occupational medicine at the University of Padua in 1972 and later in hygiene at the University of Trieste. He has been studying the relationship between cancer and cell differentiation for several years: he has isolated the differentiation factors of stem cells capable of inhibiting or slowing the growth of various types of human tumors. Lecturer for many years at the Postgraduate School of Occupational Medicine in Trieste, he currently works at the Institute of Research and Care with a Scientific Multimedia in Milan. He is the author of numerous scientific publications and some books published by Feltrinelli and Bruno Mondadori. He is President of the Foundation for the Research of Biological Cancer Therapies and Vice President of the Scientific Society “International Academy of Tumor Marker Oncology”. He is a member of the Scientific Committees of some international journals in the field of oncology and epidemiology. He is National Vice-President of WWF Italy.