Daily pill intake allows control of advanced lung cancer for seven years

Despite the National Pharmaceutical Pricing Authority (NPPA) setting a trade markup limit of 30% on the ex-factory price in February 2019, anticancer drugs have a markup of up to 700%.

An analysis shows that most drugs for which the NPPA set a trade markup ceiling of 30% in February 2019 had markups ranging from 100% to 700%, according to a list compiled by the authority in 2026.

Referencing this data, the All-India Drug Action Network group, which deals with the issue of affordable medicines, noted that a one-time reduction in the maximum retail price (MRP) is an ineffective policy tool if there is no requirement for the permanent maintenance of markup limits and consistent monitoring.

The activist group points out that one-off restrictions provide only limited relief.

Melatonin, a substance often used by people to combat jet lag or improve sleep, is attracting the attention of scientists as a possible auxiliary agent in the fight against glioblastoma—one of the most dangerous types of brain cancer.

Glioblastoma is a primary malignant tumor of the brain, most often found in adults, and is one of the most difficult cancers to treat. Its characteristic feature is that it does not grow as a compact ball that can be surgically removed; instead, it resembles weed roots, penetrating between neurons and spreading microscopic branches into healthy tissue. Because of this, even after visible parts are removed by neurosurgeons, hidden cells almost always remain.

To combat these remaining cells after surgery, radiation therapy and the drug temozolomide are used, which has been recognized as the basis of treatment since 2005 due to a large clinical study. However, the tumor is prone to recurrence, meaning regrowth.

To understand the cause of recurrences, it is necessary to examine the mechanism of action of temozolomide. This drug acts on DNA, which serves as the instruction for cell division, by 'smudging' key words. If there are too many such 'smudges,' the cell cannot copy its instructions and dies. Nevertheless, many cancer cells possess their own 'corrector'—the enzyme O6-methylguanine-DNA methyltransferase (MGMT)—capable of eliminating the most harmful damage. When the gene coding for this protein is suppressed, the effectiveness of chemotherapy is higher; when it is active, much of the anti-tumor effect is lost.

Furthermore, the tumor is heterogeneous: among its cells are those with stem cell properties, meaning they can self-reproduce and create new, treatment-resistant cancer cells, like embers igniting a fire. This heterogeneity explains why treatment may destroy many cells but leave others capable of causing the disease to return. This also justifies interest in combining interventions: if a substance hinders the survival mechanisms of cancer cells, it can increase the effectiveness of the damage inflicted by chemotherapy. This is where melatonin comes in.

Our brain produces melatonin at dusk, using it as a biological clock signaling the body's need for rest. But its function is not limited to this. Simultaneously, it participates in inflammation processes, the body's defense mechanisms, and the regulation of cellular energy. Interestingly, melatonin acts differently in different locations. In healthy cells, it usually acts as a shield against oxidative damage. In some cancer cells, conversely, it disrupts the energy production mechanism. In a study with glioblastoma cells obtained from patients, it was observed that melatonin alters the energy production and metabolic regulation of these cells, leading to their death. Other studies suggest that it also modifies the interaction between the tumor and the immune system.

The reason for this dual nature lies in the fact that cancer cells exist at the limit of capabilities: they grow rapidly, consume a lot of energy, and depend on a fragile balance. A stimulus that a healthy cell absorbs without problems can destabilize a cancer cell. The idea of combining these two molecules is simple: while temozolomide damages the 'instructions' for cancer cell reproduction, melatonin prevents its defense and repair. Their combination is like a simultaneous strike on the building and its maintenance staff.

This idea is confirmed in laboratory settings. A 2025 study showed that in glioblastoma cell cultures, the combined effect exceeded the simple sum of the effects of each substance separately. The mixture suppressed signals that help the tumor survive and become inflamed, while also activating its self-destruction mechanisms. Furthermore, melatonin slowed tumor growth in mice. However, there is an important nuance: these tumors were implanted under the animal's skin, not in the brain. The brain is a fortress protected by a barrier that prevents many substances from entering. What works on the side of a mouse's brain may not work inside the skull.

Another study conducted in 2018 concerned residual cells with stem cell properties: melatonin made them more sensitive to temozolomide, although the effect varied greatly depending on the experimental model.

Treating a brain tumor is not just about eliminating it; it is crucial to preserve memory, mood, and the ability to lead a full life. Unfortunately, chemotherapy also negatively affects the healthy brain. In this regard, there is another promising path. In mice without tumors that received temozolomide, melatonin prevented depressive behavior and weakened changes in new neuron formation, although it did not prevent anxious behavior. This is an interesting result, but it needs to be proven in humans, and we must remember that protecting healthy tissue does not automatically mean protecting the tumor.

By this point, it is easy to think that since melatonin can be bought at the pharmacy, why not take it immediately? There are at least three reasons why this should not be done. Firstly, there is dosage. Many experiments use concentrations hundreds of thousands of times higher than the natural levels achieved by our body at night. It is unknown whether a pill can reach similar levels inside the brain tumor, and whether attempting this is safe.

Secondly, there is very little human data. The main clinical study was published in 1996: a small test with 30 patients showed that those who took melatonin along with radiation therapy had better survival rates after one year. This is a noteworthy fact, but it is based on a very small group of patients, predates the advent of temozolomide, and does not answer today's question.

Thirdly, adding any substance to oncological treatment can have unforeseen consequences. Therefore, patients undergoing treatment should not take melatonin for this purpose without prior consultation with the medical team and never as a substitute for prescribed therapies.

All this means that melatonin is false hope? No. It means that a good idea has reached the most difficult test. The next step is clinical trials, which will first determine the safe dose and penetration level into the tumor, and then compare standard treatment with treatment involving melatonin. And it will not be enough to measure patient lifespan; the quality of their life, including memory and emotional state, will need to be assessed. However, there is an additional obstacle. Since melatonin is a cheap and non-patented molecule, commercial incentives to fund these studies are minimal. In this case, independent research funded by public funds is necessary. Perhaps in a few years, the hormone that helps us sleep will also help chemotherapy work better. To find out, we need not just good results in cell cultures, but patients, rigor, and time.

An experimental immunotherapy method has shown preliminary signs of activity against tumors that do not respond to other treatments. These results were presented at an international clinical trial conducted by scientists from the Princess Margaret Cancer Centre in Toronto and published today in the scientific journal Nature Medicine.

Lilian Siu, an oncologist and senior researcher from the Canadian center, stated that this study provides the first clinical evidence of the possibility of selectively activating T-cells relevant to tumors and generating anti-tumor activity. She made this statement in a release published by the University Health Network (UHN).

The researcher, who is also a professor of medicine at the University of Toronto, emphasized that the data obtained are preliminary and require confirmation in larger studies, but she considers the responses observed in some patients with limited therapeutic options encouraging.

The first phase of the START001 trial evaluated the experimental drug 'invikafusp alfa'. This drug is designed for the selective stimulation of two subgroups of T-lymphocytes, designated as Vβ6 and Vβ10, which constitute about 10% of immune system cells. According to researchers, this approach aims to concentrate the immune response specifically on cells potentially involved in fighting cancer, while avoiding excessive activation of the entire immune system. However, it has not yet been proven that this method reduces side effects.

Fifty-eight volunteers participated in the study across 10 oncology centers located in Canada, France, Spain, and the United States. The main analysis covered 52 patients with 21 different types of late-stage solid tumors. Among the 27 participants who were assigned doses for further study, four (14.8%) demonstrated an objective response, meaning a sufficient reduction in tumors to meet established clinical criteria.

In the same group, 12 patients (44.4%) recorded some degree of tumor reduction, including cases that did not meet the criteria for classification as an objective response. Regarding 18 patients whose cancers had stopped responding to previous immunotherapies, 12 of them (66.7%) achieved disease control, defined as tumor shrinkage or stabilization.

Positive reactions were noted across various types of cancer, including some forms of colorectal and lung cancer, in situations where existing immunotherapies may have limitations. Researchers also observed selective expansion of target T-lymphocytes in blood and tumors, but they stressed that the small size and diversity of the sample do not allow for definitive conclusions about efficacy, duration of response, or comparative safety.

Phase two of the trial is currently underway and is expected to provide new data on the anti-tumor activity of this treatment. The development of this drug is funded by Marengo Therapeutics, where Lilian Siu serves as a consultant and holds a capital stake.