Researchers from IIS Aragón are part of the team that has just discovered a new therapy against one of the most aggressive thyroid cancers

Rebeca Sanz, researcher at IIS Aragón, is responsible for bioinformatics of the consortium and her role has been key in identifying the mechanism by which the new therapy works in aggressive anaplastic carcinomas.

The work identifies a therapeutic agent that selectively eliminates anaplastic thyroid cancer cells, one of the most aggressive and devastating cancers for which, currently, there are few effective treatment options.

El anaplastic thyroid cancer, one of the most aggressive and devastating, currently offers few effective treatment options, with a five-year survival rate of just 5%. However, a new study carried out by researchers from the Molecular Medicine Research Center (CIMUS) and the Santiago University Hospital Complex (CHUS), both belonging to the University of Santiago de Compostela and the Galicia Health Research Institute (IDIS), directed by Clara Álvarez and José Manuel Cameselle from the Neoplasia & Endocrine Differentiation and Pathology group at CHUS, with also the participation of researchers from the IIS Aragón, opens the door to innovative therapy.

The role of Rebeca Sanz, researcher at IIS Aragónas the bioinformatics of the consortium allowed analyze international public data to reinforce what was found in this work, allowing its publication in this high-impact journal. “Our analysis of massive omics data on human cells allowed us to rule out aneuploidy (alteration in the number of chromosomes in tumor cells) as a key factor for response to therapy and focus on other aspects as determinants of the response to PIAS2b-dsRNAi.” , highlights Rebeca. Precisely, bioinformatics, a line that IIS Aragón works very actively, is crucial when analyzing and interpreting sequencing data since profiles with these characteristics are increasingly necessary in cancer studies. In addition, the prominent expert in proteomics, Román González –Prieto del CABIMER- from the University of Seville contributed with his experience to understand the mechanism by which the therapy acts in this very aggressive cancer.

The study, published in the prestigious magazine Nature Communications., identifies a therapeutic agent, PIAS2b-dsRNAi, that selectively eliminates anaplastic thyroid cancer cells without affecting healthy cells or other types of benign thyroid cancer. “This finding represents a significant advance in the fight against this very challenging disease,” says Clara Álvarez.

Attacking the root of the problem with precise therapy

The researchers discovered that an enzyme called PIAS2b plays a crucial role in the survival of anaplastic thyroid cells. Unlike normal cells or other types of cancer, these cells depend on PIAS2b for their division. This discovery provided the opportunity to design a targeted therapy that specifically targets this key enzyme.

The team designed a therapeutic agent based on double-stranded RNA (dsRNAi) transcribed in vitro, called PIAS2b-dsRNAi. This dsRNAi acts as a reverse messenger molecule, silencing the expression of the PIAS2b enzyme within anaplastic cells. As a result, these cells lose their ability to divide and die in a process known as mitotic catastrophe.

Rigorous validation and preclinical evidence

The efficacy of PIAS2b-dsRNAi was rigorously evaluated in the laboratory using cell cultures from patients with anaplastic thyroid cancer compared to cells from normal, benign, or other cancer types with a good prognosis. “The results showed that the therapeutic agent was highly selective, exclusively eliminating anaplastic cells without affecting healthy cells,” explains the USC CiMUS researcher.

To advance the evaluation of PIAS2b-dsRNAi, researchers designed preclinical trials in vivo. Tumors from patients with anaplastic thyroid cancer were implanted in mice and the results of the animals treated with the therapy were compared to a control group. Tumors treated with PIAS2b-dsRNAi stopped growing, providing strong preclinical evidence for the therapeutic potential of this agent.

Also effective in the treatment of other cancers

The research was not limited to anaplastic thyroid cancer. Studies showed that PIAS2b-dsRNAi was also effective in eliminating anaplastic cancer cells from other locations, such as pancreas, lung or stomach. This versatility opens the door to broader applications in the treatment of various types of anaplastic cancer.

These results represent a significant advance in the fight against anaplastic thyroid cancer and other types of anaplastic cancer. PIAS2b-dsRNAi therapy offers a promising alternative to the limited treatment options currently available. The researchers hope that this study will encourage pharmaceutical companies to invest in the clinical development of this therapeutic agent, with the goal of bringing it to patients as soon as possible.