Salivary gland cancer stem cells

Abstract

Emerging evidence suggests the existence of a tumorigenic population of cancer cells that demonstrate stem cell-like properties such as self-renewal and multipotency. These cells, termed cancer stem cells (CSC), are able to both initiate and maintain tumor formation and progression. Studies have shown that CSC are resistant to traditional chemotherapy treatments preventing complete eradication of the tumor cell population. Following treatment, CSC are able to re-initiate tumor growth leading to patient relapse. Salivary gland cancers are relatively rare but constitute a highly significant public health issue due to the lack of effective treatments. In particular, patients with mucoepidermoid carcinoma or adenoid cystic carcinoma, the two most common salivary malignancies, have low long-term survival rates due to the lack of response to current therapies. Considering the role of CSC in resistance to therapy in other tumor types, it is possible that this unique sub-population of cells is involved in resistance of salivary gland tumors to treatment. Characterization of CSC can lead to better understanding of the pathobiology of salivary gland malignancies as well as to the development of more effective therapies. Here, we make a brief overview of the state-of-the-science in salivary gland cancer, and discuss possible implications of the cancer stem cell hypothesis to the treatment of salivary gland malignancies.

NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem–Like Cells in Adenoid Cystic Carcinoma

“…ACC has a high recurrence rate and dismal survival in part because of its intrinsic resistance to radio- and chemotherapies (2). Existence of cancer stem cells (CSC) in ACC has been suggested (3), but their molecular identity remained elusive due to difficulties with ACC culture. Development of targeted therapies for ACC has been further complicated by lack of reliable in vitro models, as there are currently no ACC cell lines available from centralized resources, and six previously created and shared cell lines were proven to be grossly contaminated or misidentified (4).…”

Immunoprofile of c-MET/PI3K signaling in human salivary gland tumors

“…[1][2][3] The molecular events associated with their development and clinicopathologic heterogeneity are poorly elucidated. 21 The HGF/c-MET pathway has been studied in several types of cancer.…”

“…1 SGTs can be classified as benign tumors characterized by slow growth and indolent disease progression or malignant tumors that progress rapidly and are associated with low survival rates. [1][2][3][4][5] Patients with SGTs experience significant morbidity and debilitating disfigurement from therapy. Surgery is the main treatment option for malignant SGTs, but the 5-year survival rate for stages II, III, and IV is only 20% to 25%.…”

“…Surgery is the main treatment option for malignant SGTs, but the 5-year survival rate for stages II, III, and IV is only 20% to 25%. 3 Thus, there is an urgent need to better understand the mechanisms underlying the invasive behavior of these tumors in order to develop novel therapeutic strategies aimed at improving quality of life and increasing survival.…”

Uso de inibidores de Histona Deacetilase como estratégia terapêutica para sensibilizar células-tronco tumorais a quimioterapia: uma nova visão terapêutica sobre carcinomas mucoepidermoide bucais

“…As CTT são quiescentes e relacionados com altos níveis de proteínas que inibem a apoptose e regulam o reporo do DNA, essas características são importantes no processo de quimiorresistência (15,16). Adicionalmente, alguns estudos têm demostrado a presença dessas células em CME e carcinoma adenoide cístico, porém o papel dessas células na quimiorresistência não está muito claro (17) .…”