Cancer treatment remains to be one of the most pervaling questions in modern science, largely due to the complex mechanical properties of a cell membrane. These complexities play a huge role in the effectiveness of anticancer drugs, especially when focused on targeting certain tissues of a mutated cancer cell. The main focus of the presented research is to understand the challenges faced regarding the treatment of cancerous cells and how modern science is navigating these issues. To address these challenges, researchers have turned to the invocation of medical membrane models, an experimental approach to better understand the topics under discussion. Overall, the main question presents itself as: “How can science form an anticancer drug that can correctly navigate the changing membrane, while cancer treatment remains to be one of the most complicated questions in modern science, largely due to the complex mechanical properties of a cell membrane. These complexities play a huge role in the effectiveness of anticancer drugs, especially when focused on targeting certain tissues of a mutated cancer cell. The main focus of the presented research is to understand the challenges faced regarding the treatment of cancerous cells and how modern science is navigating these issues. To address these challenges, researchers have turned to the invocation of medical membrane models, an experimental approach to better understand the topics under discussion. Overall, the main question presents itself as: “How can science form an anticancer drug that can correctly navigate the changing membrane, while having minimal toxicity effects and the ability to overcome drug resistance?”
Tumor cells are very needy and, therefore, are neutral to the alteration of surrounding environmental factors. These changes include variance in glucose levels and pH, which all pair together to complicate treatment options. At the base of the issue, the cancer membrane itself is already known to be very complex, making targeted drug penetration difficult, but even harder when environmental complexities are at play. This is further compounded by the presence of drug-resistant proteins like P-glycoproteins (PGPs), which pump therapeutic agents out of the cell, reducing the effectiveness of treatment. To address this issue, researchers have created monolayer mock models of cancerous cell membranes. These models serve the purpose of studying membrane-drug interactions at the molecular level, but with isolated factors, allowing for more specific studies to be conducted. This advancement provides a clearer picture of how drugs interact with the membrane, giving insight into how we could make drugs penetrate more effectively.
Monolayer models have been one of the biggest advancements in cancer drug research. Their development has allowed for the replication of certain surface properties of cancer cells, providing a platform for adequate testing at the molecular level. The model’s main purpose is to allow scientists to isolate variables, granting the study of specific aspects such as binding properties, lipid conformation, orientation coefficient, and repellency. When these concepts are studied together, they help provide insight into how a real membrane would function in specified conditions and how said conditions affect drug penetration. These studies are critical when focusing on the development of drugs that could bypass complex membranes safely and more effectively.
Despite modern advancements in membrane studies, many of the current cancer treatments, such as chemotherapy, have major drawbacks. Specifically, treatments such as chemotherapy target quickly dividing cells, which unfortunately include healthy hair and skin cells, leading to severe side effects such as immune suppression and hair loss. An example of such a chemotherapy drug is paclitaxel, which aims to successfully disrupt cell growth, but not without those severe side effects due to hydrophobic properties and complications in penetration. These drawbacks are one of the main drivers for developing a new strain of anti-cancer medicine. This sort of development would be extremely beneficial for patients, allowing for quicker recovery times and less bodily harm.
For science to attempt to overcome these limitations, research has focused on finding alternative routes to drug development, such as lipid-based therapies. These studies focus on properties such as amino chain length, penetration, and headgroup affiliations. For example, tamoxifen, a drug used in the treatment of breast cancer, works by changing the surface charge of cancer cell membranes, therefore improving drug uptake. Similarly, ceramide, a lipid-based drug, has shown promise in reducing side effects by making the membrane more fluid, allowing drugs to penetrate more easily. Another course for drug development has been on apoptosis pathways, where, for instance, cisplatin and anthracyclines use lipid tail interactions in membranes to induce programmed cell apoptosis. By regulating and identifying these altered pathways, modern researchers aim to develop drugs that can selectively induce cell death in cancerous tissue while minimizing damage to healthy cells, helping deal with severe side effects.
The problem with most of these drugs is that, though effective, there have not been enough clinical trials to prove safety. To add to this, most membrane interactions are extremely complicated due to hydrophobic properties, and particularly through mechanisms like P-glycoproteins (PGPs). PGPs are transport proteins that act as vacuums to expel drugs from the cell. The problem is, this action makes treatments difficult regarding penetration. For science to attempt to overcome this hurdle, researchers are focusing on manipulating the properties of the cancer cell membrane to enhance drug uptake. An example of this is manually increasing membrane fluidity, which could enhance the activity of PGPs, improving drug transport into the cell, and therefore, increasing penetration. Another possibility is using MDRs (multidrug resistance proteins), which aid in bringing more drugs into the cell.
In conclusion, cancer treatment is extremely complex, and though significant research has been done, many questions are still left largely unanswered. On the contrary, scientists are quickly developing more complex and efficient biophysical and biochemical models, which are aiding in the progress of finding effective and less toxic therapy styles for cancer treatment. While the ultimate goal of creating a universally effective anticancer drug is still out of reach, ongoing research is steadily moving us closer to a solution that balances efficacy along with minimal toxicity.
SOURCE
: https://pubmed.ncbi.nlm.nih.gov/27368477/
all information is based of the presented research.