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October 22, 2019Blood AdvancesOpen Access

THPO-ASO administration reduced blood platelet count and delayed the progression of metastatic breast cancer in transgenic MMTV-PyMT mice compared to untreated controls.

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Why the study?

Platelets support pathological thrombosis and neoplastic proliferation, prompting investigators to test whether selectively silencing hepatic thrombopoietin could safely reduce platelet count and alter tumor progression.

Does THPO-ASO reduce platelet count and delay breast cancer progression in transgenic MMTV-PyMT mice?

Population

Mice, a baboon, and 6-week-old transgenic MMTV-PyMT mice

Comparison

THPO-ASO administration vs untreated controls

Design

Preclinical animal study

Key result

THPO-ASO administration reduced blood platelet count and delayed the progression of metastatic breast cancer in transgenic MMTV-PyMT mice compared to untreated controls.

Authors

TSToshiaki ShiraiARAlexey S. RevenkoJTJustin Tibbitts

Discussion

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Member takes

Overview

Platelet count in normal range may associate with thrombosis or cancer; leaves open whether cMPL modulation merits prospective trials.

Structured PICO

Does THPO-ASO reduce platelet count and delay breast cancer progression in transgenic MMTV-PyMT mice?

P
Population
6-week-old transgenic MMTV-PyMT mice that develop early ductal atypia progressing into fatal metastatic breast cancer.
I
Intervention
Murine- and primate-specific antisense oligonucleotides (THPO-ASO) targeting hepatic thrombopoietin gene (THPO) expression
C
Comparator
Untreated controls
O
Outcome
Average time to euthanasia (primary humane endpoint) at 2 cm3 combined palpable tumor volumesurrogate

Pharmacological reduction of platelet count using THPO-ASO is feasible and delays the progression of platelet-dependent pathological processes like breast cancer metastasis in a preclinical model.

Cite This Study

Shirai et al. (2019) studied Breast cancer. THPO-ASO vs. untreated controls was evaluated on Average time to euthanasia at 2 cm3 combined palpable tumor volume. THPO-ASO administration reduced blood platelet count and delayed the progression of metastatic breast cancer in transgenic MMTV-PyMT mice compared to untreated controls.

synapsesocial.com/papers/6a9eaa8704d883a0111cd477https://doi.org/10.1182/bloodadvances.2019000250
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Thrombopoietin: Biology and Clinical Applications1996 · 38 citations
  2. 2Safety and Antithrombotic Efficacy of Moderate Platelet Count Reduction by Thrombopoietin Inhibition in Primates2010 · 24 citations
  3. 3Murine thrombopoietin mRNA levels are modulated by platelet count1995 · 199 citations
  4. 4Thrombopoietin inhibition abrogates JAK2V617F clonal expansion in a murine model of myeloproliferative neoplasm2025
  5. 5Recombinant human thrombopoietin: basic biology and evaluation of clinical studies2002 · 375 citations