Related Experiment Video
Updated: Jun 5, 2026
Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver
Published on: July 31, 2016
PKMYT1 is a Targetable Vulnerability in del(17p) High-Risk Multiple Myeloma
Anaïs Schavgoulidze1, Jian Cui2, Jessica Encinas3
1Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.
Abstract:
Deletion of 17p is among the most adverse cytogenetic abnormalities in multiple myeloma (MM). By integrating RNA-seq data from patient MM cells with genetic dependency data from MM cell lines, we identified the protein kinase membrane-associated tyrosine/threonine 1 (PKMYT1) kinase, a member of the Wee family, as a potential therapeutic target in MM cells harboring del(17p). Genetic suppression or pharmacological inhibition of PKMYT1 activity with the selective inhibitor RP-6306 triggered accumulation of DNA damage, micronucleus formation and mitotic catastrophe, resulting in preferential cell death in del(17p) MM cells while largely sparing del(17p)-negative MM cells and healthy cells. RP-6306 also reduced tumor burden and extended survival in vivo in both xenograft and TP53-deficient syngeneic models. Collectively, our findings nominate PKMYT1 as an actionable target and support PKMYT1 inhibition as a biomarker-driven therapeutic strategy for patients with del(17p)/TP53-deficient MM.
Insights
Targeting PKMYT1 kinase with RP-6306 shows promise for multiple myeloma (MM) patients with 17p deletion. This approach induces cancer cell death while sparing healthy cells, offering a new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- 17p deletion is a poor prognostic factor in multiple myeloma (MM).
- Identifying targeted therapies for MM with 17p deletion is crucial.
Purpose of the Study:
- To identify novel therapeutic targets in MM cells with 17p deletion.
- To evaluate the efficacy of PKMYT1 inhibition as a targeted therapy.
Main Methods:
- Integrated RNA-sequencing and genetic dependency data from MM patient cells and cell lines.
- Utilized the selective PKMYT1 inhibitor RP-6306 in vitro and in vivo models.
- Assessed DNA damage, cell death, tumor burden, and survival.
Main Results:
- PKMYT1 was identified as a potential therapeutic target in del(17p) MM.
- RP-6306 induced DNA damage, mitotic catastrophe, and selective cell death in del(17p) MM cells.
- RP-6306 reduced tumor burden and improved survival in preclinical models.
Conclusions:
- PKMYT1 is an actionable therapeutic target for MM with 17p deletion.
- PKMYT1 inhibition represents a promising biomarker-driven strategy for del(17p)/TP53-deficient MM.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:23Abnormal Proliferation