Heterogeneity of hepatocellular carcinoma: from mechanisms to clinical implications

Abstract

Hepatocellular Carcinoma (HCC) is one of the most common types of primary liver cancer. Current treatment options have limited efficacy against this malignancy, primarily owing to difficulties in early detection and the inherent resistance to existing drugs. Tumor heterogeneity is a pivotal factor contributing significantly to treatment resistance and recurrent manifestations of HCC. Intratumoral heterogeneity is an important aspect of the spectrum of complex tumor heterogeneity and contributes to late diagnosis and treatment failure. Therefore, it is crucial to thoroughly understand the molecular mechanisms of how tumor heterogeneity develops. This review aims to summarize the possible molecular dimensions of tumor heterogeneity with an emphasis on intratumoral heterogeneity, evaluate its profound impact on the diagnosis and therapeutic strategies for HCC, and explore the suitability of appropriate pre-clinical models that can be used to best study tumor heterogeneity; thus, opening new avenues for cancer treatment.

Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles

“…Moreover, the plasticity of CSCs allows them to dedifferentiate back under various stimuli, including those provided by EVs [75]. In addition to the CSC phenotype, because of the tumor heterogeneity, other subpopulations of tumor cells can be detected within the TME [76]. Extracellular vesicles play a significant role in the transfer of an aggressive tumor phenotype to nonaggressive tumor cells, as a result of which the latter acquire the stem cell-like properties [77][78][79].…”

Covalent conjugation of AZD8055 with unsaturated fatty acids for the development of mTOR nanoblockers: increasing the therapeutic efficacy of hepatocellular carcinoma treatment

“…showed that by rationally incorporating PI-103, a PI3K/mTOR inhibitor, into liposomes improved systemic injectability and therapeutic effects. 7 Due to these encouraging data, Tang et al. first designed a nanoblocker related to AZD8055, which showed the best antitumor effect among seven tested mTORC1/2 inhibitors.…”