Epigenetic profiling of menstrual blood for precision cancer detection and prevention

Descripción del proyecto

Nuevas pruebas epigenéticas para detectar el riesgo de cáncer en la mujer

El cáncer constituye la principal causa de muerte en los países de renta alta, y los tumores ginecológicos (como el de mama, ovario y endometrio) revisten especial preocupación. Para hacer frente a esta creciente carga, es fundamental comprender las causas que subyacen al cáncer, mejorar la detección temprana y predecir el riesgo individual. Sin embargo, uno de los principales escollos es la falta de biomarcadores eficaces que informen sobre la exposición de una mujer a los factores que favorecen el cáncer. En este contexto, el proyecto EpiPrecise, financiado por el Consejo Europeo de Investigación, tiene por objeto abordar esta cuestión mediante el desarrollo de pruebas epigenéticas avanzadas centradas en los tumores ginecológicos, sobre todo que presentan riesgos genéticos como, por ejemplo, las mutaciones BRCA. Un elemento central de esta iniciativa es el perfeccionamiento de un algoritmo de deconvolución celular para analizar muestras complejas, incluida la sangre menstrual, ampliando así sus aplicaciones clínicas y mejorando las estrategias de prevención del cáncer.

Objetivo

Cancer has overtaken cardiovascular disease as the number one cause of mortality in high income countries, cancer incidence is increasing across the globe. Morbidity and mortality from womens cancers, particularly breast, ovarian, and endometrial cancers, follow or exceed these general trends in cancer incidence.
Tackling this growing cancer burden requires a multifactorial approach including understanding the fundamental drivers of cancer development; improving methods for detecting earlier those forms of cancer with the worst prognosis; predicting a persons risk of developing cancer; and identifying appropriate targets for preventing cancer. Indeed, one of the biggest obstacles in identifying tailored cancer prevention strategies is a lack of surrogate readout markers reflecting and integrating an individuals response to the cancer-initiating and cancer-promoting factors that they are exposed to during their lifetime. Our research delivers novel epigenetic tests relating to each of these key areas with an emphasis on womens cancers and those who are at an increase risk for cancer due to their underlying genetics, such as women with BRCA1 or BRCA2 mutations and women with Lynch Syndrome.
Central to the discovery and development of the epigenetic tests is a cellular deconvolution algorithm that is used to calculate the proportions of cell types within complex, mixed samples such as cervical swabs. In order to broaden the clinical utility of the tests and explore new applications, refinement and expansion of this cellular deconvolution algorithm is now required. The expansion will include cell types in menstrual blood, which is an important and understudied clinical sample type. The EpiPrecise project will deliver this refined and expanded algorithm and apply it to a test case in an area of high unmet clinical need. The refined algorithm will then be applied across the research portfolio and shared.