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[Intracellular signaling mechanisms in thyroid cancer]
Paul Mondragón-Terán1, Luz Berenice López-Hernández2, José Gutiérrez-Salinas3
1Laboratorio de Medicina Regenerativa e Ingeniería de Tejidos, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México; Subdirección de Investigación y Enseñanza, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México.
Background:
Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis.
Objective:
To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer.
Conclusions:
Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway.
Insights
Papillary thyroid cancer involves BRAF and RAS gene mutations affecting the MAPK signaling pathway. Research focuses on targeted therapies inhibiting this pathway for improved patient outcomes.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Thyroid cancer, primarily the papillary variant, is a common endocrine malignancy.
- BRAF and RAS gene mutations are key in papillary thyroid cancer pathogenesis, altering the MAPK signaling pathway.
- MAPK pathway proteins regulate crucial cellular processes and serve as diagnostic, prognostic, and therapeutic targets.
Purpose of the Study:
- To review the molecular mechanisms of BRAF and RAS gene signaling in thyroid cancer.
Main Methods:
- Literature review focusing on molecular mechanisms.
- Analysis of intracellular signaling pathways in thyroid cancer.
Main Results:
- BRAF mutations correlate with poor chemotherapy response and prognosis.
- MAPK pathway dysregulation is central to thyroid cancer development.
Conclusions:
- Ongoing research is developing molecular therapies targeting the MAPK pathway, particularly the (RET/PTC)/Ras/Raf components.
- Inhibiting the MAPK pathway, a major effector of ERK, shows promise for thyroid cancer treatment.
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