Research identifies the genes that may provide for the response of patients with immunotherapy melanoma

The tool developed in the study could optimize the choice of treatments up, evaluate researchers

Brazilian researchers took an important step towards precision medicine by identifying four genes capable of predicting with which patients with patients melanoma will not respond to immunotherapy. This type of treatment has revolutionized the fight against melanoma, the Skin cancer more aggressive and lethal, but still has a variable effectiveness and a high cost that limits its use, especially in Unified Health System (Sus). From this discovery, the idea is to create ways to identify patients suitable for treatment and therefore reduce costs in the public network.

Melanoma represents about 4% of skin tumors, but it is the most dangerous due to its high ability to spread to other organs. In Brazil, according to the National Cancer Institute (Inca)About 9,000 cases are recorded and almost 2,000 deaths per year due to the disease. It has been known for some time that melanoma has been highly immunogenic, that is, it responds well to immunotherapy, a treatment that stimulates the immune system to recognize and attach carcinogenic cells.

Among the different types of immunotherapy, the PD-1 protein block has become the standard treatment for advanced cases of melanoma. However, between 40% and 60% of patients do not respond well to this approach and can still have significant side effects. This brings clinical and economic challenges, in particular in countries such as Brazil, where access to immunotherapy in Sus is limited. Although the National Commission for the incorporation of technologies (CONITEC) has already recommended its inclusion in the public network, the high cost still prevents the adoption of treatment routines.

Genetic markers

It was faced with this scenario that the biotechnological engineer Bruna Pereira Sorroche decided to investigate whether it would have been possible to identify genetic markers that previously indicated the effectiveness of immunotherapy in individuals with melanoma. The study, financed by Fapesp through two projects, was conducted at the Molecular Oncology Research Center of Love Hospital (ex Barretos Cancer Hospital)With the guidance of Professor Lídia Maria Rebolho Batista Arantes. The results were Published in Journal of Molecular Medicine.

The research analyzed tumor samples of 35 patients with advanced melanoma treated with anti-pd-1 immunotherapy between 2016 and 2021 at the De Amor hospital. The scientist crossed these samples with data from a panel related to 579 relating to the immune system. This identified four genes – CD24, Nfil3, FN1 and KLRK1 – whose greater expression was strongly associated with resistance to treatment.

According to the study, patients with high expression of these genes had a risk 230 times greater than not responding to immunotherapy than those who had a low expression. In addition, global survival was also lower in these cases: after five years, 48.1% of patients with low gene expression were still alive, compared to only 5.9% among those with high expression.

In deep analysis it has shown that these genes are connected to the mechanisms of abandonment of the immune system and the suppression of the inflammatory response. For example, the CD24 gene acts as an immunological “checkpoint”, helping cancer to escape the action of the body defense system. FN1 is related to the progression of cancer and the formation of structures that favor the growth of cancer. Klrk1, usually involved in the activation of immune cells, can have its compromised function when deregulated, weakening the body’s response against cancer. The NFIL3 gene also plays an important role in the immune response and can contribute to the escape of the tumor.

“The increase in the expression of these four genes is related to known mechanisms of the development of cancer and immunological escape, that is, forms in which cancer can” hide “from the body defense system. This would explain why some patients do not benefit from immunotherapy, even when treatment is technically indicated,” says Sorroche.

Validation of discoveries

To validate the results, the team compared the results with the data of two independent international cohorts. The genetic signature has remained effective in providing for the response to treatment and clinical results, also with variations envisaged between the groups analyzed. One of the differentials of the study was the use of Nanostructure technology, a more accessible and economic genetic analysis platform compared to the traditional sequencing of the ARN, which facilitates its application in clinical practice, including hospitals with less resources.

Another promising aspect is that this genetic signature was also predictive in patients diagnosed still in the early stages of the disease. This indicates that the genetic profile of the tumor can be useful from the beginning of the treatment to guide the therapeutic decisions more effectively.

The team is in the technological patent phase. The idea is to create a panel using these and other genes as a commercial tool that allows you to evaluate, before the indication of the treatment, regardless of whether or not the patient has the chances of benefit of immunotherapy. “This can help doctors and health directors decide the best therapeutic path, avoiding unnecessary expenses for the treatment that can cost between $ 30,000 and $ 40,000 per month, a little practical value for most patients and also for Sus, especially if the treatment lasts years,” says Aranges, consultant of the study.

Although the research was conducted with a limited number of patients and retrospective data, sorroche and Arantes believe that the results open a promising path to customize the treatment of melanoma. This can save patients from the side effects of ineffective therapies and help to direct public resources more efficiently. “Our discovery has no precedents because the research was conducted on the basis of the genetic profile of the population served by SU, which guarantees greater adherence to the realities of public health in Brazil”, says Arans.

The next step is to expand the studies with a greater number of patients to validate the results and define a cutting value, or a minimum level of expression of the genes above which the response to the treatment would become unlikely. This panel can therefore be used as a prediction tool so that doctors can decide, more informed, as a therapeutic approach to offer to each patient. The initiative can represent a watershed for personalized oncology in Brazil.

Source: Terra

Ben

Ben Stock is a lifestyle journalist and author at Gossipify. He writes about topics such as health, wellness, travel, food and home decor. He provides practical advice and inspiration to improve well-being, keeps readers up to date with latest lifestyle news and trends, known for his engaging writing style, in-depth analysis and unique perspectives.