Cancer research is rapidly evolving, offering hope for better insights into this destructive cell behavior. We know cancer is a cell’s system gone rogue. It is when a cell does not behave, duplicate DNA, or divide as normal due to multiple reasons, including mutations. The mutations are often caused by radiation or the random errors in cell’s DNA replication (before splitting into two cells by the process of mitosis).
These hinder some parts of the cell cycle or resting states and stages of cell replication that mitosis is part of as well. Our cells have natural backup through multiple checkpoints that involve proteins binding to one another that are able to signal that everything is in order, in terms of required nutrients and cell growth, and that DNA replication is going smoothly. If not, the cell cycle is put on pause until things are fixed or, in dire conditions, it “dies” a sad cell death by apoptosis, where hydrolytic enzymes (proteins made by the cell that help cause breakdown of biological molecules) are released into the cell. This system seems pretty fool-proof, except it isn’t always — which is why cancers develop, either by the checkpoint proteins getting mutated, or the overactivity of some enzymes. Cells start to replicate uncontrollably, and can either travel through the blood to other organs, or even excrete substances that bring blood vessels closer to the cells so they receive more energy to grow. This article hopes to provide some insight into fairly new research being conducted in this field that I found interesting, which uses chemical and biochemical principles in the detection and potential treatment of cancer.
Telomerase as a biomarker of cancer
Telomerase is an enzyme, meaning it is a protein that speeds up processes in cells (just like the hydrolytic enzymes mentioned earlier). Its function is to protect our DNA caps, called telomeres, from getting too short when the DNA is replicated. In cancers, the rapid cell division and DNA replication is caused, among other things, by abnormally high telomerase levels in cells. Scientists hence use telomerase levels as a biomarker for cancer.
used synthesized pieces of DNA (self-made molecules from the building blocks that make our DNA) that were crafted to be able to interact with telomerase to have their length increased with telomere specific sequences. These sequences were able to self-assemble in the presence of synthesized branched DNA that was also added to create complexes that greatly slowed down the working of the mitochondria (yes, the powerhouse of the cell!) by attaching to its outer membrane and not allowing substances to pass through. This leads to reduced production of ATP as processes like glycolysis and oxidative phosphorylation stop. This itself leads to the slowing down of growth and division as ATP is invaluable in cells, as a molecule in chain reactions and an energy currency, however the release of cytokines is also initiated. These molecules instruct the cells to undergo apoptosis. Many techniques like time-of-flight mass spectrometry enabled the researchers to inspect the binding of molecules in this research, along with more renowned methods for this research like gel electrophoresis and assays.
Base editors, and preventing cancers
A base editor is a synthetically engineered protein using parts of CRISPR technology to be able to change one base in DNA, after reading the right sequence, and this is useful to treat diseases such as sickle cell anemia that come from a mutation from the sequence (...CTT…) to (...CAT..) in a subunit of the hemoglobin protein, for example, called a point mutation. A TED-talk by David R Liu
talked about base editors as molecular machines, simplifying their function related to genetic diseases such as sickle-cell anemia, and progeria. However, these proteins, as he mentions, can also potentially be applied to DNA sequences that are prone to often leading to cancers, which occur from germline mutations. These are sequences in reproductive cells that mutate, and since our germ cells(reproductive cells) contain these DNA sequences, this mutation gets carried on to the next generation, making offspring more prone to cancer. Hence, if the bases were to be changed back, when the cells are quite young and few, then this could reduce risk of the offspring getting cancer in theory.
Advancing tumor imaging using dissolution-DNP
Dissolution-DNP (dynamic nuclear polarization) is a technique devised to bring clearer imaging in MRI images (which is an application of NMR, nuclear magnetic resonance, which depends on the spin of particles in a magnetic field). This method, explained in detail through the research article
, talks of how the obstacles around the production and longevity of molecules that would help produce clearer imaging and portable means of performing medical imaging, not only for cancer but various other diseases, which makes MRI with the addition of DNP, a worthy competitor to CT scans or PET scans which produce images well, but use ionizing radiation which is slightly risky to use since it may cause cancer. The new methods were not only in terms of using specific chemicals such as testing different forms and processes in increasing polarization of pyruvate (a sugar molecule, produced even in our cells), but also creating devices that would allow for samples in their solid state to be loaded into the polarizer machine for use as they were quite efficient to use.
All of these experiments, though use biological principles and focus on imaging, preventing or treating cancer, tend to lean into chemistry principles and their application in the cellular biology field, to be able to study the complex behaviors of living organisms through a chemical lens.
Iman Lalani is Deputy Columns Editor. Email them at firstname.lastname@example.org