In skin cancer, melanoma is the rarest form (10%) but also the most serious. Unfortunately, its frequency has been increasing steadily for half a century. In some patients, the development of anti-cancer immunotherapies, which harness the power of an individual’s immune system to destroy tumors, has revolutionized treatment. Patients with advanced melanoma have been able to survive for years instead of months. For this category of people, the treatment only works in 40% of cases.
Today, researchers have made a major advance in the fight against melanoma. According to a study published in the journal Nature Communications, scientists from Sanford Burnham Prebys Medical Discovery Institute (California, USA) have found a new way to boost the immune system’s ability to fight the tumor.
Scientists have long known that Siah2 is involved in the processes that tumors use to grow. Here, the scientists used genetically modified mice to not produce the protein and introduced BRAF-like melanoma, which occurs in half of human melanomas. They then noticed that in the absence of the Siah2 gene, melanoma tumors shrank thanks to anti-PD-1 therapy while in mice carrying Siah2, they continued to grow.
“Find a drug that blocks Siah2”
Going further, the scientists discovered that, in mice without Siah2, the tumors were infiltrated by killer immune cells and did not have Treg cells, regulatory cells that limit the effectiveness of the immunotherapy currently used. Thus, the immune system was more efficient in eliminating tumors.
“In our study, mice lacking the Siah2 gene were able to mount an immune attack against melanoma. In addition, the efficacy of Siah2 in immunotherapy has been demonstrated for ‘cold’ tumors – those which do not respond to immunotherapy – which have been effectively eliminated by blocking PD-1 in Siah2 mutant mice ”, says Professor Ze’ev Ronai, lead author of the study.
“Although Siah2 is involved in controlling the activities that govern the development of cancer, this study offers the first direct evidence of its role in the immune system, namely in anti-tumor immunity”, he says. . Ze’ev Ronai explains: “Our study shows that a PD-1 inhibitor can be used to treat tumors that do not currently respond to this therapy, when given to mice lacking the Siah2 gene, thus providing a way to extend the effectiveness of immunotherapy. These results also justify our efforts to find a drug that blocks Siah2. ”
“Understanding the basic mechanisms of tumor immunity will ultimately help us improve the effectiveness of immunotherapy,” said Michael Rape, professor of cell biology and development at the University of California at Berkeley. . “This study reveals an important layer in the regulation of key components of immune cells that have an impact on the effectiveness of cancer immunotherapy, which highlights the need to develop inhibitors for Tregs, in which an inhibitor Siah2 is promising. ”
Melanoma can appear on healthy skin in 70 to 80% of cases
“Our discovery only fuels our sense of urgency to find a drug that inhibits Siah2. The use of an arsenal of new approaches should allow us to advance the targeting of Siah2 both in tumors and in their micro-environment ”, conclude the researchers.
In mainland France, cutaneous melanoma accounts for almost 4% of all cancers and 1.2% of cancer deaths. In 2017, 15,404 new cases were diagnosed (8,061 men and 7,343 women). In the same year, the disease resulted in 1,783 deaths (1,036 men and 747 women).
Melanoma can appear on healthy skin in 70 to 80% of cases, or result from the malignant transformation of a mole, which is why it’s important to have your suspicious moles checked regularly with a dermatologist, because when diagnosed early, melanoma can be treated well. If you have a doubt and don’t get an appointment quickly, you can always refer to the ABCDE rule (for Asymmetric, Edges, Color, Diameter and Evolution), a self-screening technique developed by specialists. According to the latter, a task or a mole with any of the following characteristics may be suspect: Asymmetry, Irregular edges, Inhomogeneous color, Diameter increasing, or Evolving rapidly.
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