RESUMEN
Resistance to platinum-based chemotherapy is a major clinical challenge in ovarian cancer, contributing to the high mortality-to-incidence ratio. Management of the platinum-resistant disease has been difficult due to diverse underlying molecular mechanisms. Over the past several years, research has revealed several novel molecular targets that are being explored as biomarkers for treatment planning and monitoring of response. The therapeutic landscape of ovarian cancer is also rapidly evolving, and alternative therapies are becoming available for the recurrent platinum-resistant disease. This review provides a snapshot of platinum resistance mechanisms and discusses liquid-based biomarkers and their potential utility in effective management of platinum-resistant ovarian cancer.
Asunto(s)
Biomarcadores de Tumor , Carcinoma Epitelial de Ovario , Resistencia a Antineoplásicos , Biopsia Líquida , Animales , Antineoplásicos , Manejo de la Enfermedad , Femenino , Humanos , Compuestos de PlatinoRESUMEN
Late diagnosis, unreliable prognostic assessment, and poorly-guided therapeutic planning result in dismal survival of ovarian cancer (OC) patients. Therefore, identifying novel functional biomarker(s) is highly desired for improved clinical management. MYB is an oncogenic transcription factor with emerging functional significance in OC. Here we examined its clinicopathologic significance by immunohistochemistry and TCGA/GTex data analyses. Aberrant MYB expression was detected in 94% of OC cases (n = 373), but not in the normal ovarian tissues (n = 23). MYB was overexpressed in all major epithelial OC histological subtypes exhibiting the highest incidence (~ 97%) and overall expression in serous and mucinous carcinomas. MYB expression correlated positively with tumor grades and stages. Moreover, MYB exhibited race-specific prognostic association. Moderate-to-high MYB levels were significantly associated with both poor overall- (p = 0.02) and progression-free (p = 0.02) survival in African American (AA), but not in the Caucasian American (CA) patients. Consistent with immunohistochemistry data, we observed significantly higher MYB transcripts in OC cases (n = 426) than normal ovary (n = 88). MYB transcripts were significantly higher in all epithelial OC subtypes, compared to normal, and its greater levels predicted poor survival in AA OC, but not CA OC, patients. Thus, MYB appears to be a useful clinical biomarker for prognostication, especially in AA patients.
Asunto(s)
Biomarcadores de Tumor , Etnicidad/genética , Expresión Génica , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Proteínas Proto-Oncogénicas c-myb/genética , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Pronóstico , Proteínas Proto-Oncogénicas c-myb/metabolismoRESUMEN
Cancer health disparities (CHDs), defined as the adverse differences in cancer incidence and mortality, are prevalent in certain racial and ethnic groups. Underlying causes of CHDs are multi-factorial and debatable. While low socioeconomic status, geographical location, lifestyle and behavioral factors are mostly believed to contribute to CHDs, regardless of ethnic and racial background, significant data now also exist to support a genetic basis of such disparities as well. Clearly, CHDs could best be understood by studying the interplay of multiple (genetic and non-genetic) factors and then translating the resulting knowledge into effective approaches for reducing the existing disparity gaps. This review article highlights these aspects in brief and calls the people of different expertise to work together to make an impact and tackle the challenges associated with CHDs.