ChromStretch

Why this study?

People with ovarian cancer can respond very differently to the same treatment. Clinical, pathology and molecular information help guide therapy, but they cannot always predict how an individual tumour will respond. We are testing whether a functional test on living tumour cells can add useful information about treatment sensitivity or resistance.

What is ChromStretch?

ChromStretch is a laboratory test developed at Erasmus MC. We expose a small number of living tumour cells to an anticancer drug and then stretch their chromatin - DNA together with its associated proteins. Using microscopy, we measure how newly copied DNA responds to the treatment.

What samples are used?

The assay requires living tumour cells. Depending on the clinical situation, these may be obtained from ovarian cancer ascites, a fresh tumour biopsy or, in some cases, pleural fluid. The study focuses on samples that contain enough viable tumour cells for the laboratory test.

What happens in this prospective study?

First, we test whether ChromStretch can be performed reliably on patient samples and produce an interpretable result. We then compare the laboratory readout with the treatment the patient receives, the clinical response and follow-up. This allows us to test whether the assay can distinguish treatment-sensitive from treatment-resistant tumours.

Which treatments are being studied?

The first clinical validation focuses mainly on platinum-based chemotherapy, an important treatment for ovarian cancer. Other treatments may also be explored when relevant to the patient sample and the study protocol.

Does the test determine a patient's treatment?

Not at this stage. During this validation study, treatment decisions are made by the clinical team according to standard care. ChromStretch results are analysed as research data and compared with the patient's later clinical response.

A research test being validated

ChromStretch is not yet a standard diagnostic test. The aim of this study is to determine whether it is technically reliable and whether its readout can predict treatment response. If validated, the long-term goal is to complement existing tests and help reduce exposure to treatments that are unlikely to work.

Why look at DNA replication?

Cancer treatments such as platinum chemotherapy damage DNA and challenge tumour cells while they copy it. Cancer cells differ in how well they protect and repair newly made DNA. Our research has shown that stressed replication sites rapidly change their chromatin - the way DNA is packaged and organised - and that these changes can help protect the DNA.

What does ChromStretch measure?

ChromStretch visualises individual chromatin fibres and measures treatment-induced changes at newly replicated DNA. The current assay focuses on H3K9me3, a chromatin mark, and RAD51, a DNA-repair protein. Together, these markers provide a functional picture of how tumour cells respond to treatment.

Why a functional test?

Genetic and molecular tests can tell us which alterations a tumor carries. ChromStretch asks a different question: what do the living tumor cells actually do when they encounter a treatment? The aim is not to replace existing tests, but to add a direct functional readout of treatment response.

How quickly can the assay provide a readout?

The laboratory workflow is designed to generate a research readout in about three days once sufficient viable tumour cells are available. A key goal of the study is to determine whether this can be achieved reliably across different patient samples.

What could this mean for patients?

If prospectively validated, ChromStretch could complement pathology and molecular testing with information about how a patient's tumour responds to a drug. Because it can work with a small number of viable cells, it may be useful when tumor material is limited. Further clinical validation is required before it can guide routine treatment decisions.

• European Research Council (ERC) Proof of Concept - PRECISE, Grant Agreement 101293351 (2026-2027).
  Project information: PRECISE on CORDIS
• Erasmus MC - Daniel den Hoed grant: AV20260003 - ChromStretch
• Oncode Institute - translational development support for ChromStretch.

Internal Collaborations:

Department of Molecular Genetics, Erasmus MC

Department of Gynaecological Oncology, Erasmus MC

Department of Medical Oncology, Erasmus MC

Department of Pathology, Erasmus MC

External Collaborations:

University Medical Center Groningen (UMCG)

Franciscus Gasthuis & Vlietland

Albert Schweitzer Ziekenhuis

• Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability Gaggioli V, Lo CSY, Reveron-Gomez N et al. (2023) Nature Cell Biology 25: 1017-1032.
• Replication-stress-induced chromatin loops protect fork stability Gaggioli V, Sengupta K, Choudhury A et al. (2026) Nature 656: 493-505.

Related patent

Methods, compositions and devices for spreading chromatin fibers Taneja N, Gaggioli V, Kanaar R. International patent application PCT/NL2023/050120; publication WO2023172142A1 (2023).

Contact us

 

Scientific lead: Dr. Nitika Taneja

Clinical lead: Dr. Ingrid Boere

Study coordination: Mikky Pieterse, MD

Technical lead: Carmen Fonseca

Email: chromstretch@erasmusmc.nl

 

Our Team

 

Dr. Nitika Taneja, PhD - Principal Investigator, Molecular Genetics

Dr. Ingrid Boere - Medical oncologist and clinical co-investigator, Medical Oncology

Dr. Heleen van Beekhuizen - Gynaecological oncologist, Head of Gynaecological Oncology

Dr. Floris Groenendijk – Pathologist, Pathology and Clinical Bioinformatics

Dr. John Martens - Head of Translational Cancer, Medical Oncology

Mikky Pieterse, MD - PhD candidate, clinical study coordination, Medical Oncology

Merel Vegter - PhD candidate, Gynaecological Oncology

Carmen Fonseca - Research Technician, Molecular Genetics