A Proposed Information–Based Modality for the Treatment of Cancer — Telling
the Tumor to Self-destruct
There are many different ways to treat cancer, but most of them involve physical manipulation of the cancer cells. For example, there is removal through surgery. There is radiation treatment, hormone therapy and chemotherapy. There is gene therapy.
I propose treating cancer through the manipulation of the information passed to the cancer cell, not the manipulation of the cell directly. The idea is to pass to the cancer cells information that will cause them to stop growing or force them to self-destruct (apoptosis).
An information-based modality might seem to be similar to gene therapy because genes are a form of information. But gene therapy changes the internal genetic mechanisms of the cell. Instead, this modality uses information to cause a change in the internal behavior.
Treatments that involve physical manipulation can often affect other cells too. This happens with many cancer drugs, leading to dangerous side effects. The advantage of using intercellular information passing is that it could be tailored to cancer. That is, the information would be ignored by most normal cells because they would not recognize or respond to the information, so it would not affect them. This would lead to individualized, targeted treatment.
This modality is based on a theory for Structure Encoding in DNA (Van der Mude, 2020). Structure Encoding Theory is an attempt to describe how the genome goes about constructing body parts. In doing so, cells need to communicate data in the local microenvironment about where in that body part they should fit. Some of this information is “analog”, that is, morphogenes that specify location by their concentration. But more precise data is most likely “digital” — it consists of strings of DNA that give a specific location.
Structure Encoding Theory
Most of the genome does not encode genes. It is considered to be non-functional, non-coding, or “junk” DNA. A large part of the non-coding DNA is made up of retroviruses, also known as transposons. Structure Encoding Theory postulates that most of the genome has a purpose: encoding the structure of body parts. Transposons and retroviruses have been incorporated into the genome (exaptated) to make this possible.
The central dogma of molecular biology focuses on genes that encode for proteins as the fundamental part of the genome. Instead, this view considers the genes as low-level functions that implement the instructions and data encoded in the bulk of the genome.
Consider an analogy. Modern-day computers typically contain only a small fraction of their memory for the operating system. The operating system typically contains thousands of little functions to perform tasks such as reading and writing files, reading the keyboard and displaying output, or communicating with the Internet. But the bulk of a typical computer memory contains things such as images and documents. This information depends on the operating system to be useful. But the operating system is just a small part of the computer.
The genome is most likely the same. As an animal or plant begins to grow, it needs information about the arrangement of body parts and the fine structure of those parts. There are a number of genes, such as the Hox genes, that code for gross structure. But there just are not enough genes to specify all of the structures in the body.
According to Structure Encoding Theory, The structure information is organized in a hierarchy. Genes such as Hox genes are at the top level, but through epigenetic differentiation, they turn on transposons and activate non-coding sequences to produce the detailed structure. This is done in a hierarchical manner through the process of deactivation by methylation. When the body part is determined, the information on the other body parts are deactivated. At that point, the next level of the structure is determined, and the other fine structure information is deactivated.
This process does two things. First, it determines the physical arrangement of the body part. This is done through cell death (apoptosis) which removes unneeded cells. Of the cells that are left, each one has a special purpose, which requires that only certain proteins are active. This is done by controlling the Gene Regulatory Network, which turns on or off the families of proteins required for a specialized cell to function.
Transposons are known as “jumping genes” because they jump into different places in the genome. According to Structure Encoding Theory, the transposons function as a way of representing three-dimensional structure in the one-dimensional DNA sequence. A way of thinking about this is to consider that the transposons are doing origami on a thread.
There must be communications between the cells so that each cell knows what part it has to play in the overall structure. Some of this communication is through analog-style morphogen gradients. But as Kerszberg and Wolpert (2007) point out: “morphogens may represent a rather crude positional information system, which is then more finely tuned by cell-cell interactions. Clearly, the morphogen gradient does not act alone and is itself specified by a variety of complex cellular mechanisms.” Structure Encoding Theory postulates that the more detailed information is passed by exosomes (extracellular vesicles) containing genetic sequences, such as the relevant transposons or other long, non-coding sequences (lncRNA) that precisely determine the structure. The exosome contains digital data in the form of the transposon to tell nearby cells where they are located in the body part.
Epigenetic Differentiation Errors As A Cause of Some Cancers
Structure Encoding Theory suggests what could be one of the causes of many cancers: in the process of epigenetic differentiation, where a generic stem cell divides to become a pluripotent cell and this divides to become a fully differentiated cell, an error either in the genetic information or in the epigenetic state leads to a neoplasm that can become cancerous. This means that cancer sometimes happens due to problems with the process of epigenetic differentiation.
Cancer is commonly defined as abnormal cell growth. Since most cells form structures in the body, many cancers can be understood in terms of the development of abnormal structures.
The degree and quality of the cancer differs depending on the stage of epigenetic differentiation when the cancer arose. Early in the process, the cell is a stem cell, leading to a cancerous stem cell. Later in the process, the neoplasm would manifest itself as an abnormal growth of a particular kind of cell, a situation that is less dangerous than if the error had occurred earlier on in the process. If it is late enough in the process, the cancer that forms could actually be somewhat benign.
If this Epigenetic Differentiation Model is correct, cancer cells should be passing exosomes containing transposons and lncRNA in the tumor microenvironment. In that case, the transposons and lncRNA that are passed by exosomes are often specific to that particular cancer, depending on which body part the cancer cell came from.
This has actually been shown to happen. Cancers are known to produce more exosomes than other cells. Exosomes with transposons and lncRNA have been identified in cancers and can be used in the identification of cancer as a biomarker.
An Information–Based Modality for Cancer Treatment
Presuming that a cancer arises in the process of epigenetic differentiation, Structure Encoding Theory leads to this Hypothesis:
Given Structure Encoding Theory and the Epigenetic Differentiation Model for cancer, many or most cancers pass structure information between the tumor cells in the form of fragments of transposons and lncRNAs. The Hypothesis is a treatment for cancer that incorporates into the tumor microenvironment information passed via exosomes to instruct the local cells to go into apoptosis. This will overwhelm the current microenvironment and force the tumor cells to self–destruct.
To test the Hypothesis, we have the following Experimental Test Sequence:
- Determine which exosomes containing transposon and lncRNA fragments cause apoptosis during the normal process of cellular differentiation. Create a library of such sequences.
- Determine which exosomes containing transposon and lncRNA fragments are associated with which cancer tumors.
- Match the transposon and lncRNA fragments in the tumor to the closest fragments that cause apoptosis.
- Create artificial exosomes containing the fragments that cause apoptosis.
- Flood the tumor with these artificial exosomes and check that this initiates apoptosis.
The first two steps will require the creation of a comprehensive catalog of transposons and lncRNA sequences and their effects during the process of epigenetic differentiation, both normal and cancerous. It may eventually be possible to develop algorithms that provide general rules for these matches. Some experimentation may be necessary to determine how to deliver the appropriate sequences to the tumor based on the current sample and incorporate them into the tumor microenvironment so that this information overwhelms the current information.
The challenge of this approach is that it is based on transposons and lncRNAs that are unique to each particular cancer. Research up to now is typically focused on transposons and lncRNAs that show up with many cancers, and the ones that are unique to each tumor are ignored. If this information–based modality is to be specific to the tumor, then the unique information being passed between the cells in the tumor will need to be identified.
But this also leads to an advantage of this approach. Since the information is unique to the specific tumor, this targeted approach is less likely to affect the patient in other ways. An information-based modality attacks the cancer in such a way that the information is ignored by the rest of the body.
References
A. Van der Mude, “Structure Encoding in DNA”, journal of Theoretical Biology, Vol. 492, 7 May 2020, 110205 https://doi.org/10.1016/j.jtbi.2020.110205
A. Van der Mude, “A Proposed Information-based Modality for the Treatment of Cancer”,Biosystems Volume 211, January 2022, 104587 https://doi.org/10.1016/j.biosystems.2021.104587
