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Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

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Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
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Targeted Cancer Therapies02:57

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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.
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Cancer Stem Cells and Tumor Maintenance02:40

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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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Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

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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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Cancer02:18

Cancer

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Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
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Related Experiment Video

Updated: Feb 19, 2026

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

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Combating subclonal evolution of resistant cancer phenotypes.

Samuel W Brady1,2, Jasmine A McQuerry1,3, Yi Qiao4

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, 30 South 2000 East, Salt Lake City, UT, 84112, USA.

Nature Communications
|November 3, 2017
PubMed
Summary
This summary is machine-generated.

Breast cancer cells evolve phenotypically to resist treatment, not just genetically. Targeting these acquired traits shows promise for adaptive cancer therapy.

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Area of Science:

  • Cancer Biology
  • Genomics
  • Translational Oncology

Background:

  • Metastatic breast cancer treatment is limited by acquired drug resistance.
  • Tumor heterogeneity and drug-refractory subclones drive treatment failure.
  • Understanding subclonal evolution is critical for improving therapeutic strategies.

Purpose of the Study:

  • To investigate the genetic and phenotypic evolution of breast cancer subclones during treatment.
  • To identify mechanisms of acquired drug resistance in metastatic breast cancer.
  • To evaluate the potential of phenotype-targeted therapies for overcoming resistance.

Main Methods:

  • Longitudinal tracking of genetic and phenotypic subclonal evolution in four breast cancer patients.
  • Utilized bulk and single-cell RNA sequencing to analyze tumor changes over time.
  • Assessed the impact of chemotherapy on subclone dominance and gene expression profiles.

Main Results:

  • Acquired genetic mutations post-chemotherapy were rare.
  • Significant phenotypic changes were observed, including enhanced mesenchymal and growth factor signaling, and decreased antigen presentation and TNF-α signaling.
  • Pre-existing subclones with resistant phenotypes were selected for by chemotherapy, indicating adaptive evolution.

Conclusions:

  • Breast cancer exhibits phenotypic evolution as a key mechanism of drug resistance.
  • Acquired malignant phenotypes can be targeted by specific therapies, showing effectiveness in post-chemotherapy cells.
  • An adaptive, phenotype-targeted treatment strategy is proposed to combat evolving cancer resistance.