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16/11/2021

Vall d'Hebron identifies a therapeutic target for the treatment of chemotherapy-resistant head and neck carcinoma

Equip Dra. Matilde Lleonart

16/11/2021

The team led by Dr. Matilde E. LLeonart has observed the presence of elevated levels of syntenin-1 in chemotherapy-resistant cells and cancer stem cells.

The Biomedical Research with Cancer Stem Cells group at Vall d'Hebron Research Institute (VHIR) has identified a key protein, syntenin-1, for head and neck squamous cell carcinoma to acquire resistance to certain chemotherapeutic treatments and also greater aggressiveness. Thus, this protein becomes a possible therapeutic target for the treatment of a type of cancer with low survival rates when diagnosed in advanced stages. The work, published in the journal Cancers, has been carried out together with the Otorhinolaryngology Service of the Vall d'Hebron University Hospital, the Central University Hospital of Asturias – Health Research Institute of Asturias Principality ISPA (Dra. Juana García-Pedrero and Dr. Juan Pablo Rodrigo), the Health Research Institute of Santiago de Compostela, Omic Sciences Department mixed Unit Eurecat- Rovira i Virgili University and the CIBER of Oncology (CIBERONC).

Resistance to treatment is the main factor impacting on the poor survival of patients with head and neck squamous cell carcinoma, caused by the appearance of new alterations in the cells throughout tumor formation. First, the researchers studied in cell culture what molecular and cellular mechanisms are related to the acquisition of resistance to chemotherapy.

They compared two groups of head and neck squamous cell carcinoma cells, sensitive and resistant to the chemotherapeutic cisplatin, and observed that syntenin-1 levels were higher in the cisplatin-resistant cells. These levels were also increased in cancer stem cells, a type of cell capable of self-renewing and forming tumors from scratch. They are responsible for tumor formation and progression. These cells are also associated with resistance to therapies, metastasis and tumor recurrence.

To confirm the role of syntenin-1, the team of researchers blocked the expression of this protein. They observed that, if syntenin-1 expression was blocked, the cells regained sensitivity to cisplatin and cell multiplication within the tumor was reduced. "Syntenin-1 could become a promising therapeutic target to eliminate resistance to cisplatin and cancer stem cells and, therefore, improve the prognosis of patients," says Dr. Matilde E. LLeonart, head of the Biomedical Research in Cancer Stem Cells group at VHIR.

In the same direction, the expression of syntenin-1 was also analyzed in tumors from 382 patients with head and neck squamous cell carcinoma. It was found that high levels of this protein were associated with greater activation of the Src protein (known for its involvement in other types of tumors), greater aggressiveness of the cancer and a worse evolution of the patients. They confirmed, therefore, that syntenin-1 has a relevant role in proliferation, migration, invasion and differentiation in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma is the sixth most common type of cancer in the world, which can affect the oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity or salivary glands. If diagnosed early, it is usually curable. Even so, patients are usually diagnosed in more advanced stages and therefore require aggressive treatment and life expectancy is lower. On many occasions this is due to resistance to treatment, tumor recurrence or the appearance of metastases.

"The design of new targeted treatments, as well as the identification of biomarkers for diagnosis and prognostic prediction, will be essential to improve the evolution of patients with head and neck squamous cell carcinoma," concludes Dr. LLeonart.

This work has been made possible thanks to funding from the Spanish Association Against Cancer (AECC) and the Carlos III Health Institute (ISCIII).

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