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USC CiMUS researchers discover a new therapy directed against anaplastic thyroid cancer without damaging healthy cells

  • 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.
  • The research results have compelling preclinical evidence and demonstrate that this therapy is also effective in other anaplastic cancers of the pancreas, lung or stomach.
  • The study has just been published in the prestigious journal Nature Communications.


Anaplastic thyroid cancer, one of the most aggressive and devastating cancers, 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), led by Clara Álvarez from the Neoplasia & Endocrine Differentiation group and José Cameselle from the Pathology Service, opens the door to innovative therapy.

The study, published in the prestigious journal 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 source 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, anaplastic 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 in vitro transcribed double-stranded RNA (dsRNAi), 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. These results are protected by an international patent application with publication number (WO2021/028610A2).

Figure: The PIAS2b protein is located for the first time in mitosis or division of the Anaplastic carcinoma cell.
PIAS2b-dsRNAi therapy depletes or eliminates PIAS2b from this mitosis, the cell is not able to continue and dies.


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 normal, benign, or other cancer types with 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, the researchers designed in vivo preclinical trials. 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. Tumours 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. The 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.



This work is the result of collaboration between clinical researchers, pathologists and surgeons from CHUS and laboratory researchers from CiMUS, both belonging to IDIS-USC. The researchers appreciate the support of SERGAS and the Health Department of the Xunta de Galicia for the organization of the TIROCHUS collection, which has allowed the consecutive collection of remnants from thyroid surgical operations. Likewise, they express their “deepest admiration for the patients” who, with their limitless generosity, have donated their tissues for research, especially to women, since this pathology is more common in them.