Related Experiment Video

Updated: Jun 22, 2025

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

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

Published on: December 11, 2017

7.2K

Programming tumor evolution with selection gene drives to proactively combat drug resistance

Scott M Leighow1,2, Joshua A Reynolds1, Ivan Sokirniy1,2

  • 1Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, USA.

Nature Biotechnology
|July 4, 2024
PubMed

Insights

This study introduces selection gene drives to redirect tumor evolution and overcome drug resistance. These engineered systems effectively eliminate diverse cancer resistance mechanisms in vitro and in vivo.

Area of Science:

  • Oncology
  • Evolutionary Biology
  • Synthetic Biology

Background:

  • Targeted anticancer therapies frequently fail due to the evolution of drug resistance.
  • Tumor genetic heterogeneity complicates the development of universally effective cancer treatments.

Purpose of the Study:

  • To engineer a novel therapeutic strategy that reproducibly redirects tumor evolution to overcome drug resistance.
  • To develop and validate a selection gene drive system for cancer therapy.

Main Methods:

  • Development of a selection gene drive system with inducible fitness advantage and shared fitness cost switches.
  • Utilizing stochastic models to define selection gene drive design criteria.
  • Prototyping drives that leverage tyrosine kinase inhibitors and diverse therapeutic mechanisms (prodrug catalysis, immune induction).
  • In vitro and in vivo (mouse models) testing against pre-existing genetic resistance.

Main Results:

  • Selection gene drives can be stably introduced into cancer cells.
  • Designed drives successfully eradicated diverse genetic resistance mechanisms in vitro.
  • Model-informed application of drives effectively targeted pre-existing resistance in mouse solid tumor models.

Conclusions:

  • Selection gene drives represent a powerful, evolution-guided framework for anticancer therapy.
  • This approach offers a reproducible method to engineer therapeutic opportunities by redirecting tumor evolution.
  • The strategy holds promise for overcoming drug resistance in diverse cancers.

More Related Videos

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

10.6K
Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli09:01

Mutagenesis and Functional Selection Protocols for Directed Evolution of Proteins in E. coli

Published on: March 16, 2011

30.5K

Related Concept Videos

Antibiotic Selection00:57

Antibiotic Selection

Overview
53.0K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

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...
3.3K
Genome Size and the Evolution of New Genes03:21

Genome Size and the Evolution of New Genes

While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
7.9K
Mutation, Gene Flow, and Genetic Drift01:09

Mutation, Gene Flow, and Genetic Drift

In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
58.3K
Gene Flow02:39

Gene Flow

Gene flow is the transfer of genes among populations, resulting from either the dispersal of gametes or from the migration of individuals.
35.0K
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
13.9K