Problem Statement Discussion on EGT and Cancer
7 August, 2024
The Problem with STP
Standard treatment protocols bombard patients with maximum tolerable drug dosage to kill as
many cancer cells as possible while minimizing detrimental side effects.
However, cancer cells develop mutations and gain resistance to the drug. In such a case, an
alternative drug is chosen and this continues till there are no options left.
This approach with a huge concoction of different drugs overloaded on the patient is very
effective but does not work for everyone.
Why EGT?
In order to come up with better STPs, we need to study and analyze the growth of tumors and
cancer cells in various conditions. Cancer is a Darwinian disease and EGT can lay out the
mathematical equations to simulate Darwinian ecological growth.
Understanding the growth of cancer cells in relation to its environment is extremely essential.
Game Theory of Cancer Treatment
Here, we consider the case where the physician becomes a true player in the game. When
viewing cancer as an evolutionary game between the physician and the cancer cells, a natural
question arises: Can we drive cancer into a stable state, corresponding to either a cure or a
chronic disease, which is not too harmful for the patient and can be maintained at a stable tumor
burden? This concept of stability corresponds to the Evolutionarily Stable Strategies introduced
in Section 2. Alternatively, if cure or stable tumor burden cannot be achieved, a relevant
question is whether we can maximally delay undesirable states (e.g., too high tumor burden or
too high level of resistance), by more dynamical treatment protocols than currently used as
SoC.
Problem #1
Application of EGT principles in therapy, in order to anticipate and steer cancer eco-evolutionary
response, is a powerful tool, but relies on our ability to estimate tumor size and composition
prior to treatment. The intra-tumoral evolutionary process leads to sub-clonal diversification and
generates the genetic and phenotypic intra-tumor heterogeneity, which determines the tumor
composition and therefore the evolutionary state. In order to optimize the model parameters,
determined by the tumor composition, monitoring of the tumor’s behavior during therapy is
required. At best, this encompasses continuous surveillance of the total number of tumor cells
and their cell type composition. In a clinic, the personalized therapeutic strategy then needs to
be optimized after every measurement, i.e., after each clinical visit.
However, in a clinical setting the key constraint is the low amount of information available about
intra-tumoral evolution and the speed of evolution during treatment. It is still challenging to
identify, quantify and monitor the evolving strategy distribution in heterogeneous tumors.
Modern imaging techniques might hold more promise than tissue and liquid biopsies. This is
because it can reveal relevant information about both the location of the lesions and the tumor
cell types within these lesions, to reveal both tumor eco-evolutionary dynamics and spatial
characteristics. The biggest obstacle to applying EGT treatment methods to clinics remains the
difficulty of estimating the tumor composition which currently can be done only for some types of
cancers. Therapy for such cancers is particularly suited for this approach. They have discrete
cell types and can therefore be understood via simpler EGT models.
CBMIR might be used for this purpose to gain real time data about tumor changes, help in personalized
treatment adjustments which is essential for cancer patients, and for predictive modeling. However, the
translation of those data into improving the model is a challenge.
Main Paper of Reference:
Full Paper
[Link]
Others:
1. Integrating evolutionary dynamics into cancer therapy J. S. Brown, Gateby
2. Game-theoretical description of the go-or-grow dichotomy in tumor development for
various settings and parameter constellations
( "Grow" tumors grow more slowly and have a less aggressive clinical course compared to "go"
tumors. They are often more localized and less likely to spread quickly.)
Problem #2
“The proliferation of progressively more complicated models is certainly a sign of a growing
subfield. But as cancer researchers, we know that growth doesn’t need to imply health. I think
we build more complicated and detailed theoretical models because we can and because it’s
relatively straightforward; not because they’re needed and not because they are having a clear
impact on cancer research (outside mathematical oncology).
For a computer scientist, abstraction is a way to hide the complexity of a computer system. It is
a way to make programs that can be used and re-used without having to re-write all the code for
each new computer. In this sense an algorithm is an abstraction of the actual sequence of bit
flips that carry out the physical process that is computation. To turn it around: the physical
process carried out by your computer is then an implementation of some abstract algorithm.
Abstraction and implementation are in some sense dual to each other.”
[From article: Abstracting evolutionary games in cancer]
Codebase Reference Links (found so far):
[Link]
[Link]
