Related Experiment Video

Updated: Oct 18, 2025

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence
06:25

Quantifying Replication Stress in Ovarian Cancer Cells Using Single-Stranded DNA Immunofluorescence

Published on: February 10, 2023

2.2K

Precision Oncology with Drugs Targeting the Replication Stress, ATR, and Schlafen 11

Ukhyun Jo1, Yasuhisa Murai1,2, Naoko Takebe3

  • 1Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892-4264, USA.

Cancers
|September 28, 2021
PubMed

Insights

Targeting DNA replication stress with ATR inhibitors offers a precision medicine approach for cancer. Schlafen 11 (SLFN11) can identify tumors suitable for this treatment, improving cancer diagnosis and therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Precision medicine utilizes tumor molecular features and drug delivery for improved cancer care.
  • Targeting DNA replication is a viable strategy due to the availability of numerous anticancer drugs.
  • Elevated replication stress (RepStress) is induced by these drugs, but selective targeting remains a challenge.

Purpose of the Study:

  • To discuss targeting DNA replication, checkpoint, and repair pathways in cancer treatment.
  • To explore the use of ATR inhibitors for cancer therapy.
  • To identify Schlafen 11 (SLFN11) as a predictive biomarker for treatment response.

Main Methods:

  • Review of molecular processes of DNA replication and its checkpoints.
  • Discussion of targeting replication, checkpoint, and repair pathways.
  • Exploitation of Schlafen 11 (SLFN11) as a predictive biomarker.

Main Results:

  • ATR inhibitors can target replication stress pathways.
  • SLFN11 is a potential predictive biomarker for identifying tumors responsive to replication-targeting drugs.

Conclusions:

  • Targeting DNA replication stress pathways with ATR inhibitors represents a precision medicine strategy.
  • SLFN11 can help select patients for this targeted therapy, addressing unmet clinical needs in cancer treatment.
Keywords:
ATRAdavoseribCamptothecinCeralasertibPARPRucaparibberzosertibcisplatinniraparibolaparibreplication stressschlafen 11talazoparibtemozolomide

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.2K
Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype14:51

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype

Published on: June 17, 2022

3.3K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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...
8.0K
DNA Damage can Stall the Cell Cycle02:37

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.5K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

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...
5.2K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.7K
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...
3.4K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.0K