Current Achievements in Oncology: New Methods and Drugs

Cancer stubbornly refuses to give up its positions. However, scientists dedicated to finding new ways to combat this deadly disease are not going to give up. We have gathered the most promising and hopeful research in the field of oncology, the results of which were presented last month.

A multitude of studies aimed at finding innovative anti-cancer methods focus on cellular mechanisms that play a crucial role in the formation and progression of malignant tumors, seeking ways to manage them so that ultimately they benefit the patient. We reviewed several such studies from the past month, including one that examined the mechanism of formation and destruction of cells in metastatic cancer.

Metastases occur when cancer cells detach from the primary tumor, spread throughout the body, and multiply in new areas. Identifying and destroying secondary cancer sites is an extremely challenging task for oncologists. In a recent study, scientists focused on autophagy—a natural process by which a cell, including a metastatic cancer cell, identifies its damaged components and "recycles" them by enclosing them in a sort of membrane bag, after which it rejuvenates.

The researchers attempted to disable the activity of lysosomes—organelles through which the cell recycles its own "waste"—and found that this deprived cells with high metastatic potential of their ability to survive. Thus, the scientists concluded that the process of metastasis could be prevented.

Acidity Matters

A Spanish-American team of researchers used a computer model to study how changes in the environment of cancer cells affect their metabolic pathways—and as a result, they were able to find a way to weaken them. According to the scientists, an alkaline environment is necessary for tumor cells to function normally—in an acidic environment, they survive poorly.

"The results of our experiment are still in the theoretical realm," admits co-author of the study Miguel Duran-Frigola. "But I believe that soon this hypothesis can be tested on animals, which will allow us to move on to more advanced stages of preclinical trials."

Another recent study revealed a cellular mechanism that, its authors hope, could significantly change the approach to cancer treatment. Scientists studied the role of so-called Wnt proteins, which regulate many processes of cell development, including their division, in the development of malignant tumors. The mechanism involving these proteins, known as the Wnt signaling pathway, provides the ability of cells to divide, and any disruptions in it can lead to the proliferation of malignant cells and cause cancer.

The researchers discovered that spiral filaments present in the cytoplasm of cells, called cytonemes, are involved in this process and play an important role in transmitting signals that control the rate of cell division, and that this process can be halted if the formation of cytonemes is prevented. They believe that new anti-tumor drugs targeting the formation of cytonemes could effectively combat cancer.

Putting Cancer Cells to Sleep

Scientists from Australia have discovered that cancer cells can be put to sleep—they developed a new class of substances capable of blocking their activity. Lead author of the experiment Ann Vos from the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia, explained that the substances they created suppress the action of proteins KAT6A and KAT6B, which are associated with certain types of oncology.

"Instead of trying to damage the DNA of tumor cells, as chemotherapy and radiotherapy do, harming the body, the drugs we developed simply put cancer cells into a permanent sleep," says Ann Vos. "The new class of substances halts the process of cancer cell division, effectively 'turning off' their ability to initiate a new life cycle." In other words, the substance triggers the natural aging process of pathologically altered cells. They do not die but can no longer divide and proliferate. Subsequently, the immune system cleanses the body of such inactive cells, just like any biological waste.

The scientists admit that they still have a lot of work to do before the new type of drugs can be tested on humans with cancer diagnoses. But they are already confident that the substances they developed could be extremely effective as part of a consolidation therapy aimed at preventing relapse after primary treatment.

What are Sprouty 1 and 2

Along with searching for vulnerabilities of cancer at the molecular level, some studies released last month focused on the natural protective mechanisms of the human body that can be "directed" towards a more vigorous fight against tumor cells. One such study proved that immune cells would more effectively attack a tumor if two key molecules—Sprouty (Spry) 1 and Spry 2—are removed.

The removal of the genes responsible for producing these molecules increased the survival of CD8 cells—a type of T-lymphocyte that is a powerful weapon of the immune system against viruses and pathogenic bacteria. This allows CD8 cells not only to become stronger in the fight against cancer but also to "remember" their enemies. So, if in the future the body encounters "enemy" cells again, the immune system will respond to the threat more quickly and effectively.

According to the scientists, the results of their study will help improve the production of CAR T cells—cells with chimeric antigen receptors used to combat malignant tumors. The method they proposed can also be used in conjunction with genome editing techniques, such as the CRISPR system, allowing for the removal of Sprouty 1 and 2 molecules from cells, making them even more effective.

Researchers from the University of California, San Diego, also recently conducted a study examining how certain genes contribute to cancer development. They found that fragments of DNA known as enhancer RNAs (eRNAs), which were previously thought to have no functional purpose, actually contain "instructions" for creating molecules that help cancer spread. The researchers discovered that eRNAs maintain the expression of genes that promote the growth of malignant tumors at the highest level. Conversely, if the amount of eRNAs is reduced, the expression of these genes also decreases.

Forcing Cancer to Self-Destruct

If previous studies focused on attempts to block the division of cancer cells, searching for their vulnerabilities and "putting them to sleep," the current study, according to its authors, examined how to make brain cancer cells destroy themselves. Scientists discovered a synthetic chemical compound that depletes the energy resources of malignant cells in mice with a highly aggressive type of brain cancer—glioblastoma.

The energy reserve of cancer cells consists of tiny organelles—mitochondria—that convert nutrients entering the body into energy. The researchers found that a substance called KHS101 blocks this mitochondrial function, disrupting metabolism in glioblastoma cells and cutting off their energy supply, which effectively leads to their self-destruction. Importantly, the scientists discovered that this approach is effective in treating the entire spectrum of genetic variations of glioblastoma cells. They also confirmed that the synthetic chemical successfully crosses the blood-brain barrier, which prevents most molecules from entering the brain and limits the possibilities of anti-cancer therapy.

"This is just the first stage of a very long process, but we hope that thanks to our discoveries, developers of anti-cancer drugs will begin to explore the possibility of using this chemical compound and that in the future KHS101 will extend the lives of many cancer patients," say the authors of the study.

Zombie Gene Protects Against Cancer

Elephants are less susceptible to cancer than humans, and this is an established fact. The authors of a recent study sought to explain this. Previously, scientists found that elephants have at least 20 copies of the p53 gene, which is involved in regulating the cell cycle and suppressing the growth of malignant tumors, while humans and most other animals have only one copy of it.

In the course of the new study, scientists discovered that p53 contains a "pseudogene" called leukemia inhibitory factor 6 (LIF6), which has the ability to "come back to life" and regenerate.

Upon reactivation, LIF6 ceases to be a pseudogene and begins to attack and destroy cells with damaged DNA. It does this by puncturing the membranes of the mitochondria of damaged cells, disrupting their permeability, blocking cellular respiration processes, and thereby preventing their potential transformation into malignant cells.

Scientists refer to LIF6 as a zombie gene because it was active in the ancestors of elephants 30 million years ago. According to them, the dead gene has come back to life. It reactivates in response to genetic errors that occur during the repair of damaged DNA. Thus, it eliminates affected cells from the body, preventing the development of cancer.