Transcriptional cyclin-dependent kinases as therapeutic targets in bone metastasizing cancers
- 1OncoBone Therapeutics Ltd.
Abstract
Cyclin-dependent kinases (CDKs) are established and emerging drug targets in cancer. Clinical success of CDK4/6 inhibitors in HR+/HER2- breast cancer has validated the CDK family therapeutically and stimulated development of both next-generation cell-cycle CDK inhibitors and inhibitors targeting transcriptional CDKs (CDK7-9, CDK11–13 and CDK19). Experience across these programs has shown that the therapeutic value of a CDK inhibitor is determined not only by kinase selectivity, but also by tumor dependency, compensatory pathways, normal-tissue biology, pharmacokinetic exposure and dosing schedule. Transcriptional CDKs are particularly attractive in cancers that depend on highly active oncogenic transcriptional programs, potentially creating a therapeutic window despite their essential roles in normal cells. In this review, we summarize CDKs as cancer drug targets with emphasis on transcriptional CDKs and metastatic disease. We specifically explore the potential of CDK9 inhibition in bone metastases, including effects on both tumor cell survival and RANKL-NF-κB -driven osteoclastogenic bone microenvironment, and discuss how CDK12 and CDK13 may provide complementary or context-dependent therapeutic opportunities.
Related
- Tarloxotinib targets tumor hypoxia to improve therapeutic efficacy of immune checkpoint inhibition in a MyD88-dependent manner.
- Emerging Roles of Src Family Protein Tyrosine Kinases in Diabetic Peripheral Neuropathy: Current Evidence and Therapeutic Perspectives.
- Skin-Derived Non-Coding RNAs as Potential Biomarkers and Therapeutic Targets
- Identification of genetically supported candidate therapeutic targets for angina pectoris using mendelian randomization
- From respiratory viral infection to persistent cough hypersensitivity: neuroimmune regulation and therapeutic implications of P2X3/TRP ion-channel targets
BibTeX
@article{kahkonen2026transcriptional,
title = {{Transcriptional cyclin-dependent kinases as therapeutic targets in bone metastasizing cancers}},
author = {Tiina E. Kähkönen and Gergana Galabova and Michael Thormann and Jussi M. Halleen},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1984003},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1984003/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptional cyclin-dependent kinases as therapeutic targets in bone metastasizing cancers
AU - Tiina E. Kähkönen
AU - Gergana Galabova
AU - Michael Thormann
AU - Jussi M. Halleen
PY - 2026
DA - 2026/10/26
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1984003
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1984003/full
AB - Cyclin-dependent kinases (CDKs) are established and emerging drug targets in cancer. Clinical success of CDK4/6 inhibitors in HR+/HER2- breast cancer has validated the CDK family therapeutically and stimulated development of both next-generation cell-cycle CDK inhibitors and inhibitors targeting transcriptional CDKs (CDK7-9, CDK11–13 and CDK19). Experience across these programs has shown that the therapeutic value of a CDK inhibitor is determined not only by kinase selectivity, but also by tumor dependency, compensatory pathways, normal-tissue biology, pharmacokinetic exposure and dosing schedule. Transcriptional CDKs are particularly attractive in cancers that depend on highly active oncogenic transcriptional programs, potentially creating a therapeutic window despite their essential roles in normal cells. In this review, we summarize CDKs as cancer drug targets with emphasis on transcriptional CDKs and metastatic disease. We specifically explore the potential of CDK9 inhibition in bone metastases, including effects on both tumor cell survival and RANKL-NF-κB -driven osteoclastogenic bone microenvironment, and discuss how CDK12 and CDK13 may provide complementary or context-dependent therapeutic opportunities.
SN - 2234-943X
ER -