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Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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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...
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Combination Therapies and Personalized Medicine02:50

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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...
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Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

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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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Receptor Tyrosine Kinases01:26

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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...
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M-Cdk Drives Transition Into Mitosis02:15

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
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M cyclin...
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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
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Dual Kinase Targeting in Leukemia.

Luca Mologni1, Giovanni Marzaro2, Sara Redaelli1

  • 1Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.

Cancers
|January 6, 2021
PubMed
Summary

Multi-targeting drugs offer a new approach to cancer therapy by simultaneously inhibiting multiple survival pathways. This review highlights dual-kinase inhibitors and novel PROTACs for treating leukemias and lymphoid tumors.

Keywords:
AMLCMLPROTAClymphomamulti-kinase inhibitors

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Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Cancer treatment often involves inhibiting multiple survival pathways to improve outcomes and prevent relapse.
  • Traditional combination therapy uses multiple drugs; however, multi-targeting drugs offer a more streamlined approach.
  • Multi-targeting drugs, which inhibit several cancer-related macromolecules simultaneously, are revolutionizing cancer treatment.

Purpose of the Study:

  • To review recent advancements in dual-kinase inhibitors for acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), and lymphoid tumors.
  • To provide an overview of preclinical studies and ongoing clinical trials involving these inhibitors.
  • To discuss emerging dual-targeting strategies, including kinase/histone deacetylase (HDAC) and kinase/tubulin polymerization inhibitors, and Proteolysis Targeting Chimeras (PROTACs).

Main Methods:

  • Literature review of preclinical studies and clinical trials.
  • Focus on dual-kinase inhibitors and their application in specific hematological malignancies.
  • Exploration of novel dual-targeting strategies and PROTAC technology.

Main Results:

  • Dual-kinase inhibitors show significant promise in preclinical and clinical settings for AML, CML, and lymphoid tumors.
  • Combination strategies involving kinase inhibitors with HDAC or tubulin polymerization inhibitors are being explored for leukemia.
  • Proteolysis Targeting Chimeras (PROTACs) represent a new frontier in targeted cancer therapy.

Conclusions:

  • Multi-targeting drugs, particularly dual-kinase inhibitors, are a significant advancement in cancer pharmacotherapy.
  • Ongoing research into novel combinations and PROTACs holds great potential for improving cancer treatment efficacy.
  • The development of targeted therapies continues to evolve, offering new hope for patients with hematological malignancies.