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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.
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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.
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Targeted therapies for ROS1-rearranged non-small cell lung cancer.

T Patil1, E Simons2, R Mushtaq1

  • 1Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Drugs of Today (Barcelona, Spain : 1998)
|November 14, 2019
PubMed
Summary

ROS1 gene fusions are key in non-small cell lung cancer (NSCLC). This review covers tyrosine kinase inhibitors (TKIs) for ROS1-positive NSCLC, including newer agents addressing resistance and brain metastases.

Keywords:
CabozantinibCancer therapyCeritinibCrizotinibDS-6051bEntrectinibLorlatinibNon-small cell lung cancer (NSCLC)ROS1 gene fusionsROS1+ NSCLCRepotrectinibTyrosine kinase inhibitors

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • ROS1 gene fusions occur in 1-2% of non-small cell lung cancer (NSCLC) cases.
  • ROS1-positive NSCLC shares characteristics with ALK-positive NSCLC, including lower smoking history and female predominance.
  • Adenocarcinoma is the most common histology in ROS1-positive NSCLC.

Purpose of the Study:

  • To review current and emerging tyrosine kinase inhibitors (TKIs) for ROS1-positive NSCLC.
  • To discuss the management of brain metastases and central nervous system progression in ROS1-positive NSCLC.
  • To highlight novel resistance mechanisms to crizotinib and the development of next-generation TKIs.

Main Methods:

  • Literature review of clinical trials and research studies on ROS1-positive NSCLC.
  • Analysis of progression-free survival data and treatment outcomes.
  • Examination of molecular mechanisms of resistance to TKIs.

Main Results:

  • Crizotinib demonstrated significant progression-free survival (19.2 months) in the PROFILE 1001 trial, leading to FDA approval.
  • Brain metastases and central nervous system progression are significant concerns in ROS1-positive NSCLC.
  • Emerging TKIs show promise in overcoming resistance to crizotinib and managing advanced disease.

Conclusions:

  • Tyrosine kinase inhibitors are crucial for managing ROS1-positive NSCLC.
  • Ongoing research is focused on developing more effective TKIs to address resistance and CNS involvement.
  • Personalized treatment strategies incorporating newer TKIs are essential for improving outcomes in ROS1-positive NSCLC.