New therapy targeting the most aggressive thyroid cancer

However, a new study carried out by researchers from the Research Center for Molecular Medicine (CiMUS) and the University Hospital Complex of Santiago (CHUS), belonging to the University of Santiago de Compostela and the Galician Health Research Institute (IDIS), led by Clara Alvarez from the Neoplasia and Endocrine Differentiation Group and José Camesel from the Pathology Service open the door to innovative therapy against the most aggressive thyroid cancer.

Study published in a prestigious journal magazine Natural communicationsidentifies therapeutic agent, PIAS2b-dsRNAi, which selectively kills anaplastic thyroid cancer cells without affecting healthy cells or other benign thyroid cancers. “This discovery represents significant progress in the fight against this very difficult disease,” says Clara Alvarez.

Targeting the root of the problem with precision therapy

Researchers have discovered that the enzyme PIAS2b plays a critical role in the survival of anaplastic thyroid cells. Unlike normal cells or other types of cancer, Anaplastic cell division is dependent on PIAS2b.

. This discovery has provided the opportunity to develop targeted therapies that specifically target this key enzyme.

The team developed an in vitro transcribed double-stranded RNA (dsRNAi) therapeutic agent called PIAS2b-dsRNAi. This dsRNA acts as a reverse messenger molecule that suppresses the expression of the PIAS2b enzyme in 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 a request for international patent with publication number (WO2021/028610A2).

Figure: The PIAS2b protein is first detected in mitosis, or cell division, of anaplastic carcinoma. PIAS2b-dsRNAi therapy depletes or eliminates PIAS2b from this mitosis, the cell cannot continue and dies.

Rigorous testing and preclinical data

The effectiveness of PIAS2b-dsRNAi has been extensively evaluated in the laboratory using cell cultures of patients with anaplastic thyroid cancer compared to normal, benign, or other types of cancer cells with a good prognosis. “The results showed that therapeutic agent was very selective

exclusively destroying anaplastic cells without affecting healthy cells,” explains the CiMUS researcher from the University of Southern California.

To speed up the evaluation of PIAS2b-dsRNAi, the researchers developed preclinical in vivo testing. Tumors from patients with anaplastic thyroid cancer were implanted into mice, and the results of treatment of animals receiving therapy were compared with a control group. Tumors treated with PIAS2b-dsRNAi stopped growing, providing compelling preclinical evidence for the therapeutic potential of this agent.

Also effective in treating other types of cancer.

The study was not limited to anaplastic thyroid cancer. Research has shown that PIAS2b-dsRNAi is also effective in killing anaplastic cancer cells from other sites, such as the pancreas, lung or stomach.. This versatility opens the door to wider application in the treatment of different types of anaplastic cancer.

These results represent significant progress 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 getting it to patients as quickly as possible.

Confession

This work is a collaboration between clinical researchers, pathologists, and surgeons from CHUS and laboratory researchers from IDIS-USC’s CiMUS.

The researchers appreciate the support of SERGAS and the Department of Health of the Province of Galicia in organizing TIROCH Collectionallowing for the sequential collection of debris from thyroid surgery.

Likewise, they express their “deepest admiration for the patients” who, with their boundless generosity, donated their tissue for research, especially women, since this pathology is more common in them.