Thus far, limited hepatic reserve, recurrence of tumor after loco-regional therapy (TACE, TARE, RFA) and significant drug resistance in these patients is unfavorable and results in treatment failure and death. This is the only available option for patients diagnosed with unresectable, metastatic, or otherwise advanced HCC. However, in this case, treatment failure occurs frequently as a result of significant drug resistance. Patients presenting with an intermediate stage of HCC may benefit from “downstaging.” Downstaging is the application and process of locoregional therapy to individual tumors located outside of acceptable transplant criteria.
The goal is to reduce the tumor burden to allow organ transplantation. This downstaging has many benefits for liver transplantation for HCC formed after liver transplantation after downstaging should work towards obtaining a 5-year survival rate, much like to those who fall within criteria for transplantation. In a cohort study by Lewandowski et al., downstaging was attempted in 86 patients between 2000 and 2008. Patients had UNOS T3 HCC and no significant limits for two to three lesions. TACE and TARE were used in a total of 86 patients with HCC beyond Milan criteria. This was not a random study—TARE was used in those in whom TACE had a low chance of tolerability. Therefore, as criteria for transplantation selection and liver allocation procedures evolve, bridging and downstaging therapies such as proton and photon therapy will play a primary role in waitlist management of patients with HCC.
Heterogeneity of HCC may be caused by stem cell markers, which is a more aggressive phenotype. Cancer stem cells, particularly with ovarian cancer, are well defined as the cells have the capacity to renew and reproduce multiple mature cell types. The two defining characteristics of a stem cell are constant self-renewal and the ability to transform into a unique adult cell type. Additionally, researchers have been speculating as to the niche that helps stem cell maintain their steaminess. The cell’s unique and important niche is made up of ECM, stromal cells, and signals. For example, developed cells split to produce daughter cells. While one remains a stem cell, the remaining cell transforms into a progenitor cell, leaves the niche, and begins a route of differentiation, which forms a well-developed and mature cell. There are three classes of stem cells: embryonic stem, somatic adult stem cells, and induced pluripotent stem cells. Embryonic stem cells are cells originating from the fetus in the embryo stage.
Specifically, the embryonic stem cells are created from the time of implantation in the uterus until the end of the second month of gestation. Embryonic stem cells refer to a specific time period, resulting in the isolation and agronomy of cells from the blastocyst. The blastocyst forms approximately five days after the egg’s fertilization. The molecular classification of ESC expresses surface markers such as CD24, CD9, and alkaline phosphatase, as well as several genes involved with pluripotency, such as SOX-2, Rex-1, SSEA-3, LIN28, Thy-1, Oct-4, and Nanog. Expression of high non-embryonic stem cells are types of stem cells that are rare cells with a very limited self-renewal period and capacity for differentiation. Many types of precursor cells are isolated in adult tissues, which leads to the concept that all tissues have their own variety of stem cells. They are responsible for replacing cells that narcotize within an organ, due to either pathological or physiological events. Adult stem cells are rare, as they do not display morphology or surface markers that would separate them from a typical mature cell.