Lucília Saraiva

Skin cancer (SC) is one of the most common types of cancer in the world population, with an increasing annual incidence rate. The p53 protein plays a crucial role in skin tumorigenesis, and its function is often compromised due to mutations induced by ultraviolet radiation (UVB). Currently, sunscreen is the most recommended agent for the prevention of SC. However, the growing incidence of this type of cancer has stressed the need for effective protective options complementary to sunscreen.

O cancro da pele (CP) é um dos tipos de cancro mais comuns na população mundial, apresentando uma taxa de incidência anual crescente. A proteína p53 tem um papel crucial na tumorigénese da pele, encontrando-se a sua função frequentemente comprometida devido à ocorrência de mutações induzidas pela radiação ultravioleta (UVB). Atualmente, o protetor solar é o agente mais recomendado para a prevenção do CP. No entanto, a crescente incidência deste tipo de cancro tem evidenciado a necessidade de identificar novas estratégias preventivas eficazes complementares ao protetor solar.

This work reports the identification of the first small-molecule selective activator of PKCdelta with promising application in colon cancer therapy.

Considering the crucial role of p53 in cancer development and dissemination, p53-targeted therapies are amongst the most encouraging anticancer strategies. Inactivation of p53 by interaction with murine double minute (MDM)2 and MDMX is a common event in human cancers bearing wild-type (wt) p53. Consistently, simultaneous inhibition of the p53 interaction with both MDMs is crucial for full p53 reactivation in cancer.

Caspases-3 and -7 play a key role in the activation of apoptosis, and therefore the search for activators of these proteases has therefore deserved particular attention in the field of antineoplasic drug discovery. This work describes the implementation of a screening system for activators of these human caspases based on yeast, a unicellular eukaryotic organism, as a simplified cell model for large-scale research. Using this approach we identified two new potential activators of caspase-7, which did not interfere with the activity of caspase-3 in yeast.

As caspases 3 e 7 desempenham um papel fundamental na ativação da apoptose e por conseguinte a procura de ativadores destas protéases tem merecido particular atenção na pesquisa de fármacos com efeito antineoplásico. Este trabalho descreve a implementação de um sistema de pesquisa de ativadores destas caspases humanas tendo como base a levedura, um organismo unicelular eucariota, como modelo celular simplificado para a pesquisa em larga escala.