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Cancer stem cells in liver cancer
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Resumo(s)
O cancro primário do fígado é o sexto tipo de cancro mais diagnosticado e a terceira
principal causa de morte relacionada com cancro em todo o mundo, com cerca de
906 000 novos casos e 830 000 fatalidades reportadas anualmente. O carcinoma
hepatocelular (HCC) e o colangiocarcinoma (CCA) são os dois cancros hepatobiliares
mais comuns, representando 75%-85% e 10%-15% dos casos de cancro,
respetivamente. Evidência acumulada sugere que uma pequena subpopulação
especializada de células cancerígenas, conhecidas como células estaminais
cancerígenas (CSCs), está implicada nos processos de iniciação, progressão,
resistência à terapêutica e recorrência tumoral.
Este trabalho oferece uma revisão abrangente da literatura existente centrada em CSCs
no fígado, visando elucidar as suas características moleculares únicas e mecanismos
celulares que contribuem para o seu comportamento agressivo e resistência às
terapêuticas convencionais.
Destacamos a heterogeneidade e a plasticidade das CSCs hepáticas, detalhando a sua
capacidade de auto-renovação, diferenciação e de iniciação de tumores. As origens
celulares dos cancros primários do fígado são descritas, abrangendo hepatócitos,
colangiócitos e CSCs. Adicionalmente, o complexo papel do microambiente hepático no
desenvolvimento e progressão do cancro do fígado é explorado, enfatizando a relação
recíproca entre o microambiente tumoral e o nicho das CSCs. Discutimos, também, os
mecanismos celulares reguladores das CSCs hepáticas, que podem servir como
potenciais alvos terapêuticos e ferramentas de diagnóstico/prognóstico. Finalmente,
esta tese realça os desafios e oportunidades associados à existência de CSCs,
discutindo o seu papel na resistência ao tratamento, bem como possíveis estratégias
para o desenvolvimento de terapêuticas personalizadas focadas nas CSCs hepáticas.
No geral, este trabalho fornece uma panorâmica ampla do papel das CSCs no
desenvolvimento e progressão dos cancros primários do fígado, delineando as suas
perspetivas terapêuticas e preparando o terreno para o desenvolvimento de tratamentos
inovadores que possam melhorar os resultados dos doentes e revolucionar a gestão do
cancro do fígado.
Primary liver cancer ranks as the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, with approximately 906,000 new cases and 830,000 fatalities reported annually. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the two most common hepatobiliary cancers, accounting for 75%-85% and 10%-15% of liver cancer cases, respectively. Accumulating evidence implicates a specialized small subpopulation of cancer cells, known as cancer stem cells (CSCs), in driving tumour initiation, progression, therapy resistance and recurrence. This work offers a comprehensive review of the existing literature focused on liver cancer stem cells, aiming to elucidate their unique molecular attributes and the mechanisms underlying their aggressive behaviour and resistance to conventional treatments. We highlight the heterogeneity and plasticity of hepatic CSCs, elucidating their ability to self-renew, differentiate, and initiate tumour formation. The cellular origins of primary liver cancers are depicted, comprising hepatocytes, cholangiocytes and CSCs. Moreover, the intricate role of the liver microenvironment in the development and progression of liver cancer is explored, emphasizing the reciprocal influences between the tumoral microenvironment and the CSC niche. We also discuss the regulatory cellular mechanisms and hallmarks of liver CSCs, which can serve as potential therapeutic targets and diagnosis/prognostic tools. Finally, this thesis highlights the challenges and opportunities associated with CSCs, discussing their role in treatment resistance, and the potential strategies for developing personalized therapies aimed at targeting hepatic CSCs. Overall, this work provides a broad overview of CSCs’ role in the development and progression of primary liver cancers, outlining their therapeutic prospects and setting the stage for the development of innovative treatments that could improve patient outcomes and revolutionize the management of liver cancer.
Primary liver cancer ranks as the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide, with approximately 906,000 new cases and 830,000 fatalities reported annually. Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the two most common hepatobiliary cancers, accounting for 75%-85% and 10%-15% of liver cancer cases, respectively. Accumulating evidence implicates a specialized small subpopulation of cancer cells, known as cancer stem cells (CSCs), in driving tumour initiation, progression, therapy resistance and recurrence. This work offers a comprehensive review of the existing literature focused on liver cancer stem cells, aiming to elucidate their unique molecular attributes and the mechanisms underlying their aggressive behaviour and resistance to conventional treatments. We highlight the heterogeneity and plasticity of hepatic CSCs, elucidating their ability to self-renew, differentiate, and initiate tumour formation. The cellular origins of primary liver cancers are depicted, comprising hepatocytes, cholangiocytes and CSCs. Moreover, the intricate role of the liver microenvironment in the development and progression of liver cancer is explored, emphasizing the reciprocal influences between the tumoral microenvironment and the CSC niche. We also discuss the regulatory cellular mechanisms and hallmarks of liver CSCs, which can serve as potential therapeutic targets and diagnosis/prognostic tools. Finally, this thesis highlights the challenges and opportunities associated with CSCs, discussing their role in treatment resistance, and the potential strategies for developing personalized therapies aimed at targeting hepatic CSCs. Overall, this work provides a broad overview of CSCs’ role in the development and progression of primary liver cancers, outlining their therapeutic prospects and setting the stage for the development of innovative treatments that could improve patient outcomes and revolutionize the management of liver cancer.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia
Palavras-chave
Primary liver cancer Hepatocellular carcinoma Cholangiocarcinoma Cancer stem cells Mestrado Integrado - 2023