tyrosine-kinase inhibitor

Overview

Tyrosine-kinase inhibitors (TKIs) are a class of Targeted therapies designed to block the activity of tyrosine kinases, enzymes that transmit growth, survival, and differentiation signals through phosphorylation-dependent signaling pathways. In oncology, TKIs are used to suppress aberrant kinase-driven tumor proliferation and are especially important in cancers driven by oncogenic kinase signaling, such as EGFR-mutant non-small-cell lung cancer, chronic myeloid leukemia, gastrointestinal stromal tumors, renal cell carcinoma, and hepatocellular carcinoma.

Clinically, TKIs are often used as monotherapy or in combination with other systemic treatments, including immunotherapy, checkpoint inhibitor, and antiangiogenic agents such as apatinib or sorafenib. Their use is shaped by substantial interpatient pharmacokinetic variability, narrow therapeutic windows for some agents, and the frequent emergence of acquired resistance. As a result, TKIs are also a major focus of therapeutic drug monitoring, resistance-genotyping, and biomarker-driven treatment selection.

Focus of Latest Publications

Recent publications on tyrosine-kinase inhibitor therapy have focused on combination strategies, resistance mechanisms, biomarker development, and practical issues in treatment monitoring. In hepatocellular carcinoma, lenvatinib was discussed in a case report as a tyrosine kinase inhibitor whose efficacy may be enhanced by arginine depletion with ADI-PEG 20. Another study in fibrotic hepatocellular carcinoma evaluated a fibroblast activation protein-α-responsive, size-transformable lipid nanoparticle co-loaded with sorafenib and doxorubicin, designed to target activated hepatic stellate cells and improve stromal penetration. This system showed Fap-α-triggered size reduction, deeper intratumoral accumulation, stromal remodeling, and superior antitumor efficacy with reduced systemic toxicity in orthotopic HCC models.

Several recent studies addressed tyrosine kinase inhibitor resistance in non-small-cell lung cancer. One investigation found that osimertinib resistance was associated with altered sphingolipid metabolism, including reduced free ceramides and increased complex glycosphingolipids, and showed that combining osimertinib with D-PDMP increased sensitivity to the drug. Another publication described a tri-modal biosensor for detecting resistance-related EGFR point mutations such as T790M in the context of EGFR tyrosine kinase inhibitor therapy, highlighting the clinical need for reliable resistance testing. In parallel, a multiplex prime editing framework was used to assay thousands of point mutations across eight oncogenes for their ability to confer resistance to four tyrosine kinase inhibitors, demonstrating a scalable approach for functional resistance screening.

In renal cell carcinoma and thyroid cancer, tyrosine kinase inhibitors were examined in the context of supportive care and treatment selection. A cluster randomized controlled trial tested the feasibility and safety of intensive systolic blood pressure control in patients initiating VEGFR tyrosine kinase inhibitors, reflecting the importance of managing treatment-related hypertension. In metastatic renal cell carcinoma, a study assessed the clinical and immunological significance of FOXO1 as a biomarker of improved response to immune checkpoint inhibitor plus tyrosine kinase inhibitor therapy. Another real-world series in metastatic non-clear cell renal cell carcinoma compared first-line immunotherapy-tyrosine kinase inhibitor therapy with tyrosine kinase inhibitor monotherapy, while a review of neoadjuvant therapy in kidney and bladder cancer noted that early tyrosine kinase inhibitor monotherapy trials in renal cell carcinoma produced limited pathologic responses.

Additional publications emphasized broader translational and clinical utility. One study developed standardized ready-to-use natural deep eutectic solvent-impregnated polypropylene fiber units for robust, high-throughput determination of tyrosine kinase inhibitors in biological fluids, aiming to improve therapeutic drug monitoring for agents with narrow therapeutic windows and variable pharmacokinetics. Together, these reports show continued interest in combining tyrosine kinase inhibitors with other therapies, understanding and overcoming resistance, and improving biomarker-guided use and monitoring across multiple cancer types.

Key Publications

• NEWJan The Combined Therapeutic Effect of Lenvatinib and ADI-PEG 20 in Advanced Hepatocellular Carcinoma: A Case Report. (In vivo (Athens, Greece), 2026, PMID 42379775): "Arginine depletion with ADI-PEG 20 may enhance the efficacy of tyrosine kinase inhibitors (TKIs) such as lenvatinib."
• NEWJun FAP-α-Responsive Size-Transformable Lipid Nanoparticles for Stromal Remodeling and Enhanced Drug Penetration in Fibrotic Hepatocellular Carcinoma. (ACS applied materials & interfaces, 2026, PMID 42328782): "This developed system, denoted as SOR/DOX@GPA-LNP, is co-loaded with sorafenib and doxorubicin and engineered with three key features: (i) a FAP-α-cleavable GPA peptide linker for TME-specific activation, (ii) FAP-α-mediated targeting of aHSCs, and (iii) a PAMAM core-mediated proton sponge activity to facilitate endosomal escape."
• May A tri-modal biosensor based on alkyne-functionalized gold nanoparticles and molecular beacon for detection of resistance-related point mutations in epidermal growth factor receptor-tyrosine kinase inhibitors. (Molecular biology reports, 2026, PMID 42171913): "Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC) is frequently driven by point mutations such as EGFR T790M."
• May Cluster Randomized Controlled Trial of Intensive Systolic Blood Pressure Control in Patients With Renal Cell or Thyroid Cancer Receiving VEGFR Tyrosine Kinase Inhibitors: ECOG-ACRIN EAQ191. (Hypertension (Dallas, Tex. : 1979), 2026, PMID 42158981): "The objective of this cluster randomized controlled trial was to determine the feasibility and safety of an intensive (systolic blood pressure [SBP] <120 mmHg) versus usual care (SBP <140 mmHg) approach to SBP control in patients with renal cell or thyroid cancer initiating VEGFR (vascular endothelial growth factor)-tyrosine kinase inhibitors."
• May Altered Sphingolipid Metabolism is Associated with Osimertinib Resistance in Nonsmall-Cell Lung Cancer. (Journal of proteome research, 2026, PMID 41988688): "Current treatment for advanced NSCLC targets EGFRm with tyrosine kinase inhibitors (TKIs)."
• Apr Clinical and immunological significance of FOXO1 as a biomarker of improved response to immune checkpoint plus tyrosine kinase inhibitor therapy in metastatic renal cell carcinoma. (European journal of pharmacology, 2026, PMID 41935603): "Predicting response to immune checkpoint inhibitor plus tyrosine kinase inhibitor (IO + TKI) therapy in metastatic renal cell carcinoma (mRCC) remains challenging."
• Jun Standardized ready-to-use natural deep eutectic solvent-impregnated polypropylene fiber units for robust and high-throughput determination of tyrosine kinase inhibitors in biological fluids. (Analytica chimica acta, 2026, PMID 41935003): "Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) is essential for individualized dosing due to their narrow therapeutic windows and pronounced pharmacokinetic variability."
• Apr Neoadjuvant Systemic Therapy in Kidney and Bladder Cancer: Current Evidence and Emerging Paradigms. (American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting, 2026, PMID 41774881): "Early trials of tyrosine kinase inhibitor monotherapy showed limited pathologic responses, while immune checkpoint inhibitor-based combinations have demonstrated feasibility, safety, and the capacity to induce pathologic responses including pCR."
• May A multiplex, prime editing framework for identifying drug resistance variants at scale. (Cell genomics, 2026, PMID 41722572): "...for their ability to confer drug resistance to four tyrosine kinase inhibitors."
• Apr Clinical outcomes of metastatic non-clear cell renal cell carcinoma: a real-world single-centre experience. (Annals of medicine, 2026, PMID 41578672): "...to assess the clinical outcomes of patients treated with first-line immunotherapy-tyrosine kinase inhibitor (IO-TKI) therapy versus TKI monotherapy."