by Dr. Vladimir Vinnitsky, M.D., Ph.D., D.Sc.
“Logic is not the science of belief, but the science of proof”
John Stuart Mill
To Our Visitors
This website provides an overview of the
Oncogerminative Theory of Cancer Development.
Theory Overview Video:
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Why Oncogerminative Theory is different
Theory Highlights
Theory innovative ideas
Theory Practical Impact
For whom this site is designed
Our Mission
Why Oncogerminative Theory is different
The Oncogerminative Theory of Cancer Development is a fundamentally different theory, one that holds that the initiation of a cancer involves a desperate asexual self-cloning event in which cancer stem cells develop the ability to mimic the genetic program of germline cells, and explains tumor formation as a dynamic self-organizing process that mimics the self-organizing process of the early blastula-stage of embryo development.
Theory Highlights
Cancer is associated with a unique sort of biological immortality. The Oncogerminative Theory of Cancer Development postulates that cancer is a desperate attempt of the mortal somatic cell to achieve immortality through germinalization: the reprogramming of that cell into a pseudo-germline cell, which is a cancer stem cell. We introduced the term “oncogerminative cell” to describe a cancer stem cell. The oncogerminative cell achieves immortality through pseudo-embryogenesis, by creation of an endless line of intermediate generations of pseudo-clones that are malignant tumors. Therefore, a malignant tumor is a product of the life cycle of an oncogerminative cell just as an embryo is a product of the natural life cycle of a germline cell. Thus, we consider cancer development as a phenomenon of developmental biology, which we call a “desperate asexual self-cloning event”.
When developing a malignant tumor, an oncogerminative cell follows the same biological principles that a germ-line cell does when it develops a blastocyst-stage embryo. A malignant tumor is a mimic blastocyst-stage embryo with heterogeneous cell composition, which arises from an oncogerminative cell as it passes through its natural life cycle. The theory holds that having cancer is the same as gestating a “bad embryo”. To get rid of the cancer, the host body needs help in order to “give birth” to the malignant tumor forcibly. Ideally that means the removal of a “critical mass” of cancer cells combined with the overcoming of selective immune tolerance toward the remaining metastatic cancer cells.
There are seven innovative ideas that the Oncogerminative Theory adds to our understanding of cancer biology:
First, it states that the essence of the malignant transformation of the somatic cell is the awakening of the germline cell’s phenotypic properties in this cell. This means that the transformation of a somatic cell into a CSC (an oncogerminative cell) is driven exclusively by those genomic mutations and epigenomic alterations that result in “germinalization” of somatic cells, i.e., that result in their being reprogrammed into pseudo-germline cells. Mimicking the behavior of a fertilized germline cell, the oncogerminative cell achieves immortality by passing through the stages of its life-cycle and developing into a pseudo-blastula-stage embryo, which manifests in the body as a malignant tumor.
Second, it considers tumor formation as a dynamic self-organizing process that mimics a self-organizing process of early embryo development. Our Theory explains the initiation of cancer as a phenomenon of developmental biology, which we have called a “desperate asexual self-cloning event”. In mammals this phenomenon manifests as cancer development, which represents a desperate attempt of the oncogerminative cell to realize its potential immortality through pseudo-embryogenesis, that is, by creation of an endless line of intermediate generations of pseudo-clones that are malignant tumors.
Third, it postulates that the interaction between a malignant tumor and a host should be considered in the context of the interaction between a pseudo-embryo and a host. This means that the diagnostic and therapeutic value of new findings in malignant cells and malignant tumors should be evaluated by a comparative study of similar findings in embryo cells and embryo tissues.
Fourth, it postulates that in order to initiate the development of a metastatic tumor, a circulating CSC must first create a multicellular tumor spheroid, just as a fertilized germ cell creates a multicellular blastocyst-stage embryo before its implantation.
Fifth, our Theory explains the body’s immune tolerance to cancer embryonic antigens as a natural “phylogenetic immune tolerance” that underlies maternal immune tolerance to the antigens of an early embryo. We believe that the reason for “phylogenetic immune tolerance” to early embryonic antigens is the absence in the host of long–lived memory cells that can give rise to effector cells against these antigens. Cancer, as a pseudo-embryo that produces embryonic antigens, usurps the phylogenetic immune tolerance for its own benefit.
Sixth, it considers a postnatal immunization with tumor-associated embryonic antigens as a promising approach to overcome immune tolerance to cancer cells by inducing the appearance of the corresponding long-lived immunological memory cells, which in turn will provide lifetime immunity against cancer and significantly reduce cancer risk. Thus, our Theory suggests strategies for more effective cancer prevention: the development of effective cancer vaccines using tumor-embryo cross-reacting antigens for early-life immunization aimed at creation of life-long immunity against cancer.
Seventh, the Oncogerminative Theory proposes a new oncogerminative model of cancer development. This model explains the 5 basic stages of tumorigenesis: 1) the reprogramming (i.e. germinalization) of a somatic cell into a pseudo-germline cell that is a CSC; 2) parthenogenetic-like multiplication of CSCs and formation of a multicellular tumor spheroid with a heterogeneous cell population, which is a pseudo-blastocyst-stage-embryo; 3) vascularization of the tumor spheroid and its further invasive growth as a vascularized tumor that mimics the implantation and invasive behavior of the blastocyst-stage embryo; 4) disaggregation of the CSC compartment of the tumor into individual CSCs and their migration into body tissues, which mimics primordial cell migration; 5) development of new generations of metastatic tumors with a modified ratio of malignant to non-malignant cells that underlie tumor progression. All these events occur in the context of natural selective immune tolerance to the embryonic antigens of the cancer, which we have termed “phylogenetic immune tolerance”.
The Oncogerminative Theory’s Practical Impact:
The Oncogerminative Theory suggests innovative strategies for translational cancer research that have the potential to revolutionize cancer prevention and treatment.
The Theory will help to focus the attention and efforts of researchers on the following tasks: (i) Explore the key genes that are responsible for the reprogramming (i.e. germinalization) of a somatic cell into a pseudo-germline cell and develop gene therapies targeting somatic cells to prevent this reprogramming. (ii) Develop targeted therapies to selectively destroy CSCs, the only cells that are able to initiate development of malignant tumors. (iii) Identify tumor markers indicative of the development of tumor spheroids and their implantation and invasive properties, and develop advanced anti-cancer therapies targeting the formation of tumor spheroids. (iv) Explore natural defense mechanisms associated with embryo development that control invasiveness, immune tolerance, and the phenotypic profile of cells, and use these natural defense mechanisms in the development of targeted anti-cancer therapies. (v) Develop advanced anti-cancer vaccines based on embryonic-antigens for neonatal use as preventive vaccines, which are intended to prevent cancer from developing in healthy people. Develop fetal tissue vaccines that are intended to treat an existing cancer by restoring the body’s natural defenses against the cancer. (vi) Develop advanced combined therapies that include the removal of a “critical mass” of CSCs followed by the restoration of host immune reactivity against the remaining cancer cells, similar to a maternal host restoring her immune sensitivity to the remaining embryonic cells in the postpartum period.
We believe that the Oncogerminative Theory of Cancer Development will serve as a road map in cancer research and that using that road map to develop targeted anti-cancer therapies should allow us to prevent, control or eradicate cancer.
For whom this site is designed:
This site is designed for cancer researchers who are experts in molecular biology, immunology, cell biology, developmental biology, biochemistry, chemistry, pharmacology, biotechnology and other oncology-related disciplines, and who are eager to apply their expertise to the challenge of cancer.
This site is for members of the public who are concerned about the progress in cancer prevention and treatment. At this site you will learn about an effective way to concentrate both scientific efforts and financial support on targeted solutions to the most challenging aspects of cancer prevention and treatment.
This site is for decision-makers in federal and private R&D institutions that are dedicated to finding cancer solutions. This site will help them fulfill their mission to promote basic and applied research that may lead to breakthrough advances in cancer prevention and treatment.
Our mission:
Educate: to provide a comprehensive understanding of cancer biology, the nature of cancer stem cells, biological laws of malignant tumor development, and to identify prospective approaches to target-based cancer prevention and treatment.
Concentrate: to provide professionals with a theoretical base to concentrate their efforts on solutions to the most challenging aspects of cancer prevention and treatment. To establish a new branch of oncology: Comparative Cancer and Embryo Development Research.
Promote: to promote basic and applied research dedicated to target-based cancer prevention and treatment.
Our website provides essential information for scientists in both the academic and private sectors working in cancer research and focused on development of targeted cancer therapeutics. It also provides insights for government institutions that develop and finance strategic scientific research programs aimed at cancer prevention and cancer eradication.