Nuclear Receptors: Mechanistic Insights into Endocrine Resistance in Prostate and Breast Cancers
Macrina Beatriz Silva-Cázares,
Stephanie I. Nuñez-Olvera,
Ricardo Hernández-Barrientos,
Enoc Mariano Cortés-Malagón,
María Elizbeth Alvarez-Sánchez,
Jonathan Puente-Rivera
Affiliations
Macrina Beatriz Silva-Cázares
Unidad Académica Multidisciplinaria Región Altiplano, Universidad Autónoma de San Luis Potosí, Carr a Cedral km 5+600 Ejido San José de las Trojes, Matehuala, San Luis Potosi 78700, Mexico
Stephanie I. Nuñez-Olvera
Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
Ricardo Hernández-Barrientos
Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
Enoc Mariano Cortés-Malagón
División de Investigación, Hospital Juárez De México, Mexico City 07760, Mexico
María Elizbeth Alvarez-Sánchez
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México (UACM), San Lorenzo 290, Col. Del Valle, Mexico City 03100, Mexico
Jonathan Puente-Rivera
División de Investigación, Hospital Juárez De México, Mexico City 07760, Mexico
This review focuses on the pivotal roles of nuclear receptors (NRs) in driving endocrine resistance in prostate and breast cancers. In prostate cancer (PCa), androgen receptor (AR) amplification, mutations, and altered coactivator interactions sustain tumor growth under androgen deprivation therapy (ADT), leading to castration-resistant prostate cancer (CRPC). Orphan NRs like RORβ, TLX, and COUP-TFII further contribute to CRPC by regulating stemness and therapeutic resistance mechanisms. In breast cancer, NRs, including estrogen receptor alpha (ERα), androgen receptor (AR), glucocorticoid receptor (GR), and liver receptor homolog-1 (LRH-1), modulate estrogen signaling pathways and alternative survival mechanisms like PI3K/AKT/mTOR and NFκB, promoting resistance to endocrine therapies such as tamoxifen. Understanding these NR-mediated mechanisms is critical for developing targeted therapies to overcome endocrine resistance and improve patient outcomes in hormone-dependent cancers.
