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Related Concept Videos

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...
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...
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...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...
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:

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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

New targets for Ph+ leukaemia therapy.

Giovanni Martinelli1, Ilaria Iacobucci, Cristina Papayannidis

  • 1Department of Hematology/Oncology L. and A. Seràgnoli S.Orsola Malpighi Hospital, University of Bologna, Bologna, Italy. giovanni.martinelli2@unibo.it

Best Practice & Research. Clinical Haematology
|December 5, 2009
PubMed
Summary

Philadelphia chromosome-positive leukaemias (Ph+ leukaemias) have improved outcomes with tyrosine kinase inhibitors (TKIs), but new genetic alterations necessitate novel therapies. This review highlights promising drugs targeting mutations and leukaemia stem cells.

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Area of Science:

  • Oncology
  • Hematology
  • Genetics

Background:

  • Tyrosine kinase inhibitors (TKIs) have improved outcomes for Philadelphia chromosome-positive (Ph+) leukaemias, including chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL).
  • Despite TKI advancements, disease progression and relapse remain significant challenges for the majority of patients.
  • Recent research has identified novel genetic alterations impacting key cellular pathways in Ph+ leukaemias.

Purpose of the Study:

  • To review recent findings on genetic alterations in Ph+ leukaemias.
  • To highlight novel therapeutic strategies and emerging drugs for treating adult BCR-ABL-positive leukaemias.
  • To discuss the clinical development of new TKIs and other targeted therapies.

Main Methods:

  • Analysis of BCR-ABL point mutations.
  • Gene expression profiling (GEP) analysis.
  • Single nucleotide polymorphism (SNP) array analysis.

Main Results:

  • Identification of multiple novel genetic alterations affecting lymphoid differentiation, cell cycle, tumour suppression, apoptosis, and drug responsiveness.
  • GEP analysis revealed several differentially expressed genes.
  • SNP array analysis frequently identified deletions in genes such as IKAROS, PAX5, and CDKN2A-CDKN2B.

Conclusions:

  • New therapeutic approaches, including novel TKIs (dasatinib, nilotinib, bosutinib), are in clinical development.
  • Emerging aurora kinase inhibitors and Smo1/Hedgehog inhibitors show promise against specific mutations (e.g., Bcr-Ab T315I) and leukaemia stem cells.
  • This review identifies promising drugs for the treatment of adult BCR-ABL-positive leukaemias.