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Publication
Extracellular vesicles in liver cancer
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Abstract(s)
O cancro do fígado, particularmente o carcinoma hepatocelular e o colangiocarcinoma, continua a ser um desafio para a saúde global. É o sexto cancro mais diagnosticado e a terceira causa de morte oncológica a nível mundial. O cancro do fígado desenvolve-se tipicamente a partir de doenças hepáticas crónicas e cirrose, com etiologias diversas, incluindo infeções virais, distúrbios metabólicos, consumo excessivo de álcool e colangite esclerosante primária, entre outras. O prognóstico não é favorável devido ao diagnóstico em fases avançadas, quando as opções terapêuticas são limitadas.
Estudos recentes destacaram o papel central das vesículas extracelulares (VEs) na progressão do cancro do fígado, oferecendo novas perspetivas sobre os mecanismos da doença e potenciais estratégias terapêuticas. As VEs, incluindo exossomas e microvesículas, são partículas nanométricas, secretadas por praticamente todos os tipos de células. Elas mediam a comunicação intercelular através da transferência de moléculas bioativas, como proteínas, ácidos nucleicos e lípidos. No cancro do fígado, as VEs contribuem para o crescimento tumoral, evasão imunitária, angiogénese, metástase e resistência a fármacos. De facto, influenciam vários processos chave como a remodelação do microambiente tumoral, a modulação imunitária e a formação dos nichos pré-metastáticos, contribuindo para um ambiente favorável ao tumor, o que torna o cancro mais agressivo e de difícil tratamento. Dada a sua estabilidade, proteção contra a degradação enzimática, presença em praticamente todos os fluidos biológicos e capacidade de refletir a heterogeneidade tumoral e o estado da doença, as VEs têm elevado potencial como biomarcadores não invasivos para diagnóstico precoce, prognóstico e aplicações terapêuticas. No âmbito terapêutico, as VEs revelam-se promissoras como sistemas de entrega de fármacos, devido à sua baixa imunogenicidade e elevada biocompatibilidade. Além disso, estratégias direcionadas para as VEs incluem a inibição da sua secreção, o bloqueio da sua captação ou a eliminação das VEs circulantes. Por fim, as VEs podem também ser utilizadas como vacinas para ativar as células imunes e restaurar a imunidade antitumoral.
Apesar dos avanços consideráveis, subsistem desafios na padronização das técnicas de isolamento, na identificação de biomarcadores fiáveis e na transposição dos resultados da investigação para a prática clínica. A investigação contínua é fundamental para desbloquear totalmente o potencial de diagnóstico e terapêutico das VEs no cancro do fígado.
Liver cancer, particularly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), remains a major global health challenge. It is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Liver cancer typically arises from chronic liver diseases and cirrhosis, with several etiologies such as viral infections, metabolic disorders, excessive alcohol consumption, and primary sclerosing cholangitis, among others. The prognosis is poor, mainly due to late-stage diagnosis when treatment options are severely limited. Recent research has highlighted the pivotal role of extracellular vesicles (EVs) in liver cancer progression, offering new insights into disease mechanisms and potential therapeutic strategies. EVs, including exosomes and microvesicles, are nanosized particles secreted by nearly all cell types. They mediate intercellular communication by transferring bioactive molecules such as proteins, nucleic acids, and lipids. In liver cancer, EVs contribute to tumor growth, immune evasion, angiogenesis, metastasis, and drug resistance. In fact, they influence several key processes, such as tumor microenvironment remodeling, immune modulation and the formation of pre-metastatic niches, which help to create a tumor-friendly environment that makes liver cancer more aggressive and challenging to treat. Given their stability, protection from enzymatic degradation, presence in virtually all body fluids, and ability to reflect tumor heterogeneity and disease state, EVs hold great potential as non-invasive biomarkers for early diagnosis, prognosis, and therapeutic applications. Therapeutically, EVs offer promise as drug delivery systems due to their low immunogenicity and high biocompatibility. Additionally, strategies targeting EVs include inhibiting their secretion, blocking their uptake, or eliminating circulating EVs. Finally, EVs can also be used as immune vaccines to activate immune cells and restore anti-cancer immunity. Despite significant progress, challenges remain in standardizing isolation techniques, identifying reliable biomarkers, and translating research into clinical practice. Continued research is critical to fully unlock the diagnostic and therapeutic potential of EVs in liver cancer.
Liver cancer, particularly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), remains a major global health challenge. It is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Liver cancer typically arises from chronic liver diseases and cirrhosis, with several etiologies such as viral infections, metabolic disorders, excessive alcohol consumption, and primary sclerosing cholangitis, among others. The prognosis is poor, mainly due to late-stage diagnosis when treatment options are severely limited. Recent research has highlighted the pivotal role of extracellular vesicles (EVs) in liver cancer progression, offering new insights into disease mechanisms and potential therapeutic strategies. EVs, including exosomes and microvesicles, are nanosized particles secreted by nearly all cell types. They mediate intercellular communication by transferring bioactive molecules such as proteins, nucleic acids, and lipids. In liver cancer, EVs contribute to tumor growth, immune evasion, angiogenesis, metastasis, and drug resistance. In fact, they influence several key processes, such as tumor microenvironment remodeling, immune modulation and the formation of pre-metastatic niches, which help to create a tumor-friendly environment that makes liver cancer more aggressive and challenging to treat. Given their stability, protection from enzymatic degradation, presence in virtually all body fluids, and ability to reflect tumor heterogeneity and disease state, EVs hold great potential as non-invasive biomarkers for early diagnosis, prognosis, and therapeutic applications. Therapeutically, EVs offer promise as drug delivery systems due to their low immunogenicity and high biocompatibility. Additionally, strategies targeting EVs include inhibiting their secretion, blocking their uptake, or eliminating circulating EVs. Finally, EVs can also be used as immune vaccines to activate immune cells and restore anti-cancer immunity. Despite significant progress, challenges remain in standardizing isolation techniques, identifying reliable biomarkers, and translating research into clinical practice. Continued research is critical to fully unlock the diagnostic and therapeutic potential of EVs in liver cancer.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Biomarkers Cholangiocarcinoma EV-based therapeutics Extracellular vesicles Hepatocellular carcinoma Mestrado Integrado - 2024