Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary

Abstract

Epigenetic alterations are a common hallmark of human cancer. Single epigenetic markers are starting to be incorporated into clinical practice; however, the translational use of these biomarkers has not been validated at the 'omics' level. The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings, addressing an unmet need in the diagnostic and clinical management of these patients. Despite the great diagnostic advances made in the past decade, the use of traditional diagnostic procedures only enables the tissue of origin to be determined in ∼30% of patients with CUP. Thus, development of molecularly guided diagnostic strategies has emerged to complement traditional procedures, thereby improving the clinical management of patients with CUP. In this Review, we present the latest data on strategies using epigenetics and other molecular biomarkers to guide therapeutic decisions involving patients with CUP, and we highlight areas warranting further research to engage the medical community in this unmet need.

Cáncer metastásico con primario desconocido. Una revisión

“…Por el contrario, la supervivencia en el grupo de pronóstico desfavorable en promedio es de 6 meses a 7 meses incluso con tratamiento (quimioterapia) (1,6,7,24). Los subgrupos de pronóstico desfavorable son:…”

“…No obstante el mal pronóstico, los investigadores no han perdido el interés y, por el contrario, cada día tienen más entusiasmo y se esfuerzan por investigar y desarrollar múltiples pruebas, entre ellas los estudios endoscópicos, imágenes diagnósticas funcionales, inmunohistoquímica, perfil genético y análisis epigenético (6,7,36).…”

“…En el 10%-30% de los casos, no se logra encontrar el tumor que origina la metástasis aun después realizar una búsqueda exhaustiva con las técnicas más avanzadas -como el perfil molecular-e incluso después de la autopsia (4). Debido a la gran dificultad para encontrar el sitio primario y ofrecer un tratamiento específico, recientemente se han investigado nuevas formas de actuar frente a este tumor en las que se incluyen estudios moleculares, imagenológicos, de inmunohistoquímica y genéticos, que permitan mejorar la supervivencia de estos pacientes (2,(4)(5)(6)(7).…”

CUP Syndrome

“…Molecular tumor profiling (MTP) kits for this are commercially available that use RNA or DNA similarity analyses to identify the primary tumor (15). Additionally, analyses using multiple epigenetic alterations (e.g., the methylation profile of metastases) to identify the primary tumor have recently been published (16,17).…”

Towards personalized computational oncology: from spatial models of tumour spheroids, to organoids, to tissues

“…With respect to cancer treatment, the goal is to match each patient with the most accurate and effective treatment, without the need to create pharmaceuticals for each individual tumour. Recently, several research groups have discussed this concept in the context of melanoma, lung, breast and gastrointestinal tumours [4,5], as well as biomarker development, analyses of histomorphology and epigenomics [6,7].…”