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Many cancer treatments today are like bombing an entire city to demolish a single building. Although they save many lives, they are often challenging. They attack the DNA of cancer cells, but they also end up damaging some healthy cells. The result is known side effects, such as hair loss, nausea and a weakening of the immune system.
Much of the current efforts in oncology research are focused on reducing these collateral damages. Our team, from UFSC (Federal University of Santa Catarina), is seeking to develop a new way to achieve this objective.
Our project is still in its initial phase, but we intend to replace classic bombers with guided molecular missiles. Imagine a treatment in which the drug acts exclusively on tumor cells. The result could be more efficient, precise and less painful chemotherapy for patients.
THE CHALLENGE OF SPECIFICITY
Curing cancer is a complex challenge because the term describes it. Efficient treatments for one type of tumor may not work for others, as each type has its own particularities. However, what we seek is to explore their similarities.
One of the keys to this development is . It is now understood that some genes are more susceptible to mutations than others and play a fundamental role in the maintenance of tumor cells. In many cases, it is the . Once we know these molecular targets, the challenge becomes chemical: how to create a compound that only finds this genetic address?
Many genes associated with cancer have little structural difference from others that are not involved in this process. Therefore, most current drugs lack the necessary selectivity, resulting in damage at various points in the genome. It is exactly in this technological bottleneck that our research works. Combining the power to destroy chemical compounds with the precision of localizing specific proteins.
A NATURAL SWITCH
At the interface between chemistry and biotechnology, we are developing a protein that combines the ability to recognize specific DNA sequences with the function of cutting this genetic material. This is what we call hybrid nucleases.
To do this, we chemically improve proteins known as transcription factors – which already have them – and use them as a GPS system.
In our research, we use a protein derived from marine bacteria Erythrobacter litoralis. In nature, this bacteria uses sunlight to obtain extra energy, in a special type of photosynthesis that does not produce oxygen.
To do this, it uses a protein called EL222, which works like a . When it receives light, it changes shape and starts to bind to DNA, activating some genes. When the light goes out, it returns to its initial state.
Our interest is to take advantage of this natural mechanism to create a tool that can be turned on or off on light command. Thus, we can only activate it when it is in the tumor cell.
MOLECULAR MISSILE
But it’s not enough to be activated at the right time. The missile still needs to reach the correct address and remain attached to the target long enough to act. Then, we connected to this protein some small organic compounds capable of degrading the tumor gene.
We then tested how the chemical structure of the compound influences its effectiveness at degrading DNA. We focus on optimizing spacers, which are like carbon strings that connect the protein to the molecule that breaks down the genetic material.
We found that by increasing the length of these spacers, we were able to tune the compound’s affinity for DNA. If the chain is too short, the molecule breaks away easily. If it is long and flexible in the right way, it molds itself to the crevices of the DNA double helix, greatly increasing the stability of the bond.
THE ENEMY’S WEAPON AGAINST HIMSELF
In addition to these mechanisms, we also added other chemical groups to the original protein, capable of connecting to metals, which help to deactivate the functioning of the diseased cell. Certain metals bind to DNA and prevent its replication and this strategy is already used in some chemotherapy drugs. For example, it uses platinum, which is foreign to our body.
In our laboratory, we focus on the use of essential metals such as copper. In addition to being better tolerated by the body, we take advantage of a peculiar characteristic of the tumor environment. As tumors grow quickly and need to activate several metabolic processes, copper participates in several of these biological reactions. Therefore, many tumor cells end up capturing and storing more copper than normal cells.
Our strategy is . The organic molecules that we attach to proteins work like a molecular magnet. They navigate through the body and, upon reaching the tumor cell, capture the copper available in the environment to activate its cutting capacity. Therefore, the scissors are only sharp when they are in the right place, drastically minimizing the chances of attacking healthy tissue.
CURRENT AND FUTURE STEPS
Our first trials focused on validating this new mechanism. We produce molecular hybrids and test them in vitro its ability to sequester copper and degrade DNA. We demonstrated that it is possible to combine proteins that recognize specific genes using chemical compounds activated by copper.
So far, our results indicate that molecular missiles are capable of executing this mechanism in a specific way. We assessed that the integrity of other DNA sequences is preserved, while only the target sequence is degraded. The next step will be to investigate this in cells and look for which tumor genes we will try to silence using this system.
We are still far from a medicine, but the interesting thing is that it is a new approach. Something never done before by other research groups. Although we are in the basic science phase, these advances pave the way for the medicine of the future. Understanding how these molecular tools operate allows us to dream of a scenario where cancer treatment stops being a generalized intervention and becomes a personalized action.
This text was originally published by , on June 19, 2026. The content is free for republication, citing the source, and has been adapted to the standard of Poder360.
