YBX1 Promotes Drug Resistance in Hepatocellular Carcinoma and Serves as a Potential Therapeutic Target

Manish Tripathi1, Veerababu Nagati1, Dennis Kwabiah1

  • 1The University of Texas Rio Grande Valley.

Research Square
|April 17, 2026
PubMed

Insights

Y-box binding protein 1 (YBX1) drives drug resistance in hepatocellular carcinoma (HCC). Inhibiting YBX1 with SU056 shows promise in overcoming sorafenib resistance and reducing tumor size in HCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Drug resistance significantly worsens outcomes for hepatocellular carcinoma (HCC) patients.
  • Tyrosine kinase inhibitors (TKIs) are first-line HCC therapy but face resistance.
  • Mechanisms underlying TKI resistance in HCC remain incompletely understood.

Purpose of the Study:

  • To investigate the role of transcription factor Y-box binding protein 1 (YBX1) in mediating HCC drug resistance.
  • To validate YBX1 as a potential therapeutic target for overcoming drug resistance in HCC.

Main Methods:

  • Analysis of YBX1 expression in human HCC patient cohorts.
  • In vitro studies using HCC cell lines to assess the impact of YBX1 overexpression and knockdown on drug resistance.
  • In vivo studies using small-molecule inhibitor SU056 to target YBX1 in HCC models.

Main Results:

  • Increased YBX1 levels correlate with HCC aggressiveness, metastasis, and poor survival.
  • YBX1 overexpression confers sorafenib resistance, enhancing cell survival and tumorigenic features.
  • YBX1 knockdown or inhibition with SU056 reduces HCC cell viability and tumor growth in vivo.

Conclusions:

  • Y-box binding protein 1 (YBX1) is a key transcription factor driving sorafenib resistance in hepatocellular carcinoma.
  • Targeting YBX1 presents a promising therapeutic strategy to overcome drug resistance and improve HCC patient prognosis.

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
Hepatic Drug Excretion: Influencing Factors01:16

Hepatic Drug Excretion: Influencing Factors

The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
783
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.2K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.4K
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
72
Hepatic Drug Excretion: Enterohepatic Cycling01:17

Hepatic Drug Excretion: Enterohepatic Cycling

Enterohepatic cycling involves the active secretion of drugs and their metabolites into the bile via transporters in the canalicular membrane of hepatocytes. This secretion is an integral part of the digestive process, releasing these substances into the gastrointestinal (GI) tract.
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
3.4K