Related Experiment Video

Updated: Jun 8, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

Third-generation tyrosine kinase inhibitors and beyond

Alfonso Quintás-Cardama1, Hagop Kantarjian, Jorge Cortes

  • 1Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Seminars in Hematology
|September 30, 2010
PubMed

Insights

Imatinib resistance in chronic myeloid leukemia (CML) affects one-third of patients. Newer tyrosine kinase inhibitors (TKIs) offer improved responses, with investigational agents targeting resistance mutations showing promise.

Area of Science:

  • Hematology
  • Oncology
  • Pharmacology

Background:

  • Imatinib is the standard first-line therapy for chronic myeloid leukemia (CML).
  • Approximately one-third of CML patients exhibit resistance or intolerance to imatinib.
  • Limited therapeutic options exist for patients failing imatinib, including second-generation tyrosine kinase inhibitors (TKIs).

Purpose of the Study:

  • To review the therapeutic landscape for CML patients failing imatinib therapy.
  • To discuss the role of second-generation TKIs and emerging third-generation TKIs and non-ATP mimetic compounds.

Main Methods:

  • Literature review of clinical studies and therapeutic guidelines for CML management.
  • Analysis of treatment outcomes for patients receiving imatinib, second-generation TKIs, and investigational agents.

Main Results:

  • Second-generation TKIs (nilotinib, dasatinib) achieve complete cytogenetic response in about 50% of imatinib-refractory CML patients.
  • Allogeneic stem cell transplantation (SCT) remains an option for some patients.
  • Third-generation TKIs and non-ATP mimetic compounds demonstrate promising activity against resistant mutations, including T315I.

Conclusions:

  • Sequential TKI therapy is crucial for managing imatinib-resistant CML.
  • Investigational agents targeting specific mutations offer new hope for patients with limited treatment options.
  • Further research is needed to establish the long-term efficacy and duration of responses with newer TKIs.

More Related Videos

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

Related Concept Videos

Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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 specific...
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 specific...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
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...