Combining Chemistry and Engineering for Hepatocellular Carcinoma: Nano-Scale and Smaller Therapies

Abstract

Primary liver cancer, or hepatocellular carcinoma (HCC), is a major worldwide cause of death from carcinoma. Most patients are not candidates for surgery and medical therapies, including new immunotherapies, have not shown major improvements since the modest benefit seen with the introduction of sorafenib over a decade ago. Locoregional therapies for intermediate stage disease are not curative but provide some benefit. However, upon close scrutiny, there is still residual disease in most cases. We review the current status for treatment of intermediate stage disease, summarize the literature on correlative histopathology, and discuss emerging methods at micro-, nano-, and pico-scales to improve therapy. These include transarterial hyperthermia methods and thermoembolization, along with microfluidics model systems and new applications of mass spectrometry imaging for label-free analysis of pharmacokinetics and pharmacodynamics.

Tumor Microenvironment Alters Chemoresistance of Hepatocellular Carcinoma Through CYP3A4 Metabolic Activity

“…However, these studies did not investigate the regulation of cellular metabolism, including CYP3A4 activity, under different microenvironmental conditions ( 26 , 27 , 33 , 34 ). Recent work extending these efforts has demonstrated significant potential in utilizing collagen tunability to replicate native microenvironment properties (pH, stiffness, fiber properties, and porosity) ( 35 , 36 ), demonstrating promise in replicating physiological TME to investigate the modulation of CYP3A4 activity and chemoresistance.…”

Cytotoxicity and Apoptosis Induction of 6,7-Dehydroroyleanone from Taiwania cryptomerioides Bark Essential Oil in Hepatocellular Carcinoma Cells

“…Hepatocellular carcinoma, primary liver cancer, is one of the main leading causes of cancer-related death in the world; major therapies are surgical resection, liver transplant, radio frequency ablation, chemotherapy, immunotherapy, etc. Medicinal drugs include sorafenib, lenvatinib, regorafenib, cabozantinib, and ramucirumab; hepatocellular carcinoma still lacks more effectual pharmacotherapies [10,11]. Many researchers are devoted to finding the promising chemicals from plant natural products for hepatocellular carcinoma treatment.…”

Inhibiting p21-activated kinase (PAK7) enhances radiosensitivity in hepatocellular carcinoma

“…2 Currently, the prevalence of HCC has been increasing annually, making it a major public health issue. 2,3 So far, surgery remains the major method for HCC, 4 but many patients have lost the opportunity of surgical treatment at the time of diagnosis, since HCC is always featured with hidden onset, inconspicuous early symptoms and rapid progression. 5 As for the significant progress in the development of radiotherapy technique, like intensity-modulated radiation therapy (IMRT), helical tomotherapy and stereotactic radiotherapy, radiotherapy has become the necessary method for treatment of HCC.…”