Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers

Abstract

Hepatobiliary, pancreatic, and gastrointestinal cancers account for 36% of the ten million deaths caused by cancer worldwide every year. The two main reasons for this high mortality are their late diagnosis and their high refractoriness to pharmacological treatments, regardless of whether these are based on classical chemotherapeutic agents, targeted drugs, or newer immunomodulators. Mechanisms of chemoresistance (MOC) defining the multidrug resistance (MDR) phenotype of each tumor depend on the synergic function of proteins encoded by more than one hundred genes classified into seven groups (MOC1-7). Among them, the efflux of active agents from cancer cells across the plasma membrane caused by members of the superfamily of ATP-binding cassette (ABC) proteins (MOC-1b) plays a crucial role in determining tumor MDR. Although seven families of human ABC proteins are known, only a few pumps (mainly MDR1, MRP1-6, and BCRP) have been associated with reducing drug content and hence inducing chemoresistance in hepatobiliary, pancreatic, and gastrointestinal cancer cells. The present descriptive review, which compiles the updated information on the expression of these ABC proteins, will be helpful because there is still some confusion on the actual relevance of these pumps in response to pharmacological regimens currently used in treating these cancers. Moreover, we aim to define the MOC pattern on a tumor-by-tumor basis, even in a dynamic way, because it can vary during tumor progression and in response to chemotherapy. This information is indispensable for developing novel strategies for sensitization.

Localized Therapeutic Approaches Based on Micro/Nanofibers for Cancer Treatment

“…Chemotherapy is a drug-based treatment to destroy cancer cells [ 17 , 19 ]. This treatment is used to reduce the tumor before surgery or to delay its growth until surgery [ 17 , 20 ]. Classical chemotherapeutic agents have their primary effect on macromolecular synthesis or function, contributing to cell death.…”

“…Therefore, in selecting an effective drug, it is necessary to find an agent that has a marked inhibitory or growth-controlling effect on cancer cells and a minimal toxic effect on the host. Even so, there are several side effects in the body such as fatigue, nausea, loss of appetite and hair, and even blood clots [ 17 , 20 ]. Combination chemotherapy is a grouping of medications that is usually more effective in producing responses and prolonging life than medications used separately (monotherapy) and sequentially [ 17 ].…”

Comparative Study between the 3D‐Liver Spheroid Models Developed from HepG2 and Immortalized Hepatocyte‐Like Cells with Primary Hepatic Stellate Coculture for Drug Metabolism Analysis and Anticancer Drug Screening

“…Recent reports indicated that the high expression of MRP2 relates to chemoresistance in HCC patients resulting in low efficacy of HCC treatment. [39,40] Therefore, the current developed 3D-HepG2 coculture model may be useful for studying the mechanism of drug resistance and predicting efficacy of novel anticancer drugs for HCC treatment. The highest MRP2 expression in 3D-imHC mono and coculture models was observed at day 10 (Figure 4B).…”

ABCB1 overexpression through locus amplification represents an actionable target to combat paclitaxel resistance in pancreatic cancer cells

“…Paclitaxel also potentiates gemcitabine efficacy by increasing intratumor uptake and inhibiting its inactivation by catabolizing enzymes [ 10 , 11 ]. Mechanisms underlying paclitaxel resistance in PDAC are poorly understood [ 12 , 13 ]. Three studies have investigated paclitaxel resistance in PDAC, reporting that it involves metabolic adaptation [ 14 ], sustained c-MYC activation [ 15 ], and expression of orexin receptor type 1 [ 16 ].…”