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Updated: Feb 13, 2026

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Identification and Experimental Validation of Triosephosphate Isomerase 1 as a Functional Biomarker of SHetA2

Laura F Mortan1,2, Zitha Redempta Isingizwe1,3, Doris Mangiaracina Benbrook1,2,3

  • 1Gynecologic Oncology Section, Stephenson Cancer Center, University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.

Cells
|February 12, 2026
PubMed
Abstract

Insights

Triosephosphate isomerase 1 (TPI1) predicts ovarian cancer response to SHetA2. Higher TPI1 levels correlated with sensitivity, and modulating TPI1 affected drug potency, identifying TPI1 as a potential biomarker.

Area of Science:

  • Oncology
  • Biochemistry
  • Pharmacology

Background:

  • Identifying predictive biomarkers for investigational cancer drugs is crucial for personalized treatment.
  • SHetA2 is an investigational drug undergoing phase 1 trials for advanced or recurrent solid tumors.
  • Understanding patient response to SHetA2 in ovarian cancer requires biomarker discovery.

Purpose of the Study:

  • To identify and validate protein biomarkers predicting ovarian cancer patient response to SHetA2.
  • To investigate the role of Triosephosphate isomerase 1 (TPI1) in SHetA2 sensitivity.

Main Methods:

  • Ascites-derived ovarian cancer cell cultures were used to assess sensitivity to SHetA2 and olaparib.
  • Protein expression (including TPI1) was measured using microcapillary electrophoresis.
  • TPI1 levels were modulated via siRNA and lentivirus vectors; metabolite analysis was performed using mass spectrometry.

Main Results:

  • Elevated TPI1 levels were significantly associated with SHetA2 sensitivity in ovarian cancer ascites-derived cultures (q-value = 0.0003).
  • The majority of cultures were olaparib-resistant yet SHetA2-sensitive, with higher TPI1 in olaparib-resistant cases.
  • Modulating TPI1 expression directly impacted SHetA2 drug potency in ovarian cancer cell lines (p < 0.05).
  • SHetA2 treatment altered downstream metabolites in glycolysis, the TCA cycle, and the pentose phosphate pathway.

Conclusions:

  • Triosephosphate isomerase 1 (TPI1) is a strong candidate biomarker for predicting SHetA2 sensitivity in ovarian cancer.
  • TPI1's functional role in metabolic pathways affected by SHetA2 supports its utility as a biomarker.
Keywords:
SHetA2TCA cycleascitesbiomarkerglycolysishigh grade serous ovarian carcinomaolaparibpentose phosphate pathwayspheroidstriosephosphate isomerase 1

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