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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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Lung Capacity01:47

Lung Capacity

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Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
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Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
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Adaptive Mechanisms in Cancer Cells02:53

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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
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Targeting HER2 Aberrations in Non-Small Cell Lung Cancer with Osimertinib.

Shengwu Liu1, Shuai Li2,3, Josephine Hai1

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
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Osimertinib shows efficacy against HER2 aberrations in lung cancer. Combination therapy with JQ1 enhances response in HER2-mutant non-small cell lung cancer, supporting clinical trials.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • HER2 (ERBB2) aberrations are oncogenic drivers in 2-6% of lung adenocarcinomas.
  • HER2 amplification confers resistance to EGFR tyrosine kinase inhibitors (TKIs).
  • Limited data exist on targeting HER2 aberrations in non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • To evaluate the preclinical efficacy of osimertinib against HER2 aberrations in NSCLC.
  • To identify potential combination therapies for HER2-mutant NSCLC.

Main Methods:

  • Generated three genetically modified mouse models (GEMM) for HER2 alterations in NSCLC.
  • Tested osimertinib efficacy in vivo against these models.
  • Investigated combination therapy with osimertinib and BET inhibitor JQ1.

Main Results:

  • Osimertinib demonstrated efficacy in HER2 wild-type overexpression and EGFR del19/HER2 models.
  • Osimertinib was ineffective against HER2 exon 20 insertion tumors.
  • Combined osimertinib and JQ1 significantly improved response rates in HER2-mutant NSCLC.

Conclusions:

  • Osimertinib exhibits robust antitumor activity against various HER2 aberrations in lung cancer.
  • Combination therapy with JQ1 enhances osimertinib's efficacy in HER2-mutant NSCLC.
  • Supports clinical trials for osimertinib, alone or with epigenetic drugs, for NSCLC patients with HER2 aberrations.