Markers predicting platinum resistance in ovarian cancer

A method for assessing platinum drug resistance through the detecting of RNA modifications encapsulated within extracellular vesicles (EVs) released from ovarian cancer tissue

Advantages

  • The markers in EVs derived from tissues extracted from patients through biopsy or alternative methods, holding the potential to lead to a reliable testing methodology.
  • Novel diagnostics using RNA modifications in EVs as markers.
  • Development to create a simple kit can be expected if antibodies against the RNA modifications are obtained.

Technology Overview & Background

In the treatment of ovarian cancer, following the surgical excision of the malignancy, platinum-based chemotherapy such as the combination of carboplatin (a famous platinum drug) and paclitaxel became the gold standard. Despite it being reported that over 80% of ovarian cancer patients initially respond to platinum-based chemotherapy, more than half of patients experience recurrence due to platinum resistance, coupled with severe side effects imposing a substantial physical burden. Therefore, determining sensitivity to platinum-based drugs before initial treatment can alleviate the physical burden on patients and significantly reduce medical costs. Despite reported candidate molecules for drug sensitivity diagnostic markers, none have been implemented in clinical practice due to insufficient sensitivity and specificity.

The researcher’s group developed a methodology for collecting tissue specific EVs from cancerous tissues removed during surgery. Given that cancer tissue derived EVs faithfully reflect the in vivo environment and can be compared with normal tissues, the expectation is the derivation of highly reliable marker candidates.

In this study, researchers focused on ovarian cancer, investigating RNA modifications within cancer tissue derived EVs and successfully identifying marker candidate’s characteristic of ovarian cancer and predictive of platinum drug resistance. Future detection of these marker candidates through antibodies is anticipated.

Data

  • Researchers examined the RNA modifications in EVs derived from normal ovarian tissue and ovarian cancer tissue, confirming the marker candidates characteristically contained in EVs from cancer tissues.
  • Examination of platinum-resistant and platinum-sensitive ovarian cancer patient-derived EVs confirmed the marker candidates characteristically contained in platinum-resistant cancer tissues.
  • The area under the curve (AUC) for the best-performing marker candidate in this study was 0.79. Marker measurements were conducted using mass spectrometry.

Patents

Patent applied (not published)

Principal Investigator & Academic Institution

Kentaro Jingushi, PhD (Specially Appointed Associate Professor/ Lecturer, School of Pharmaceutical Sciences, Osaka University, Japan)

Development Stages & Plans

  • Clinical samples have been utilized for discovering candidate markers characteristically in platinum-resistant ovarian cancer.
  • Clinical samples were provided from collaborating institutions.
  • Further enhancement in diagnostic performance is anticipated through the combination of these markers.
  • Researchers are actively seeking collaboration with diagnostics and pharmaceutical companies interested in the product development of diagnostic technology for platinum drug resistance utilizing these markers.
  • Collaboration opportunities are also sought with companies for the acquisition of antibodies against the identified RNA modifications.

 

Project No. TT-04723

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