%0 Journal Article
%T A retrospective study on the mechanism underlying quick transfer from response to resistance in a repeated recurrent chordoma patient with molecular alterations treated with Palbociclib.
%A Zhong N
%A Yu D
%A Yang M
%A Lu X
%A Zhang Q
%A Wei W
%A Jiao J
%A Yang X
%A Zhu Z
%A Chen S
%A Xiao J
%J J Cancer Res Clin Oncol
%V 150
%N 2
%D 2024 Feb 19
%M 38369555
%F 4.322
%R 10.1007/s00432-023-05560-x
%X OBJECTIVE: There is no approved targeted therapy for chordoma at present. Although several preclinical studies have implied the potential applicability of CDK4/6 inhibitor for this rare tumor, no clinical evidence has been documented so far. The purpose of this study was to elucidate the therapeutic efficacy of CDK4/6 inhibitor for chordoma.
METHODS: The next generation sequencing (as for whole-exome sequencing, WES assay) and immunohistochemical (IHC) staining of the chordoma tissue from a patient with an advanced lesion were performed before treatment. Then, the patient was treated with Palbociclib for 4 months until progression occurred in the 5th month. Surgical resection was implemented and the tumor tissue was obtained postoperatively for assessment of molecular alterations.
RESULTS: Molecular features of the tumor before medical treatment suggested applicability of CDK4/6 inhibitor and the patient showed partial response (PR) according to Choi Criteria after 4 months treating with Palbociclib until progression occurred. Then, a drastic molecular alteration of the tumor as represented by emergence of dramatic E2F amplification, which is known to induce CDK4/6 independent cell-cycle entry and progression after treatment, was detected. The findings in this patient demonstrated tumor evolution under drug pressure.
CONCLUSIONS: The findings of the present study suggest the feasibility of Palbociclib for the clinical treatment of chordoma, and imply the necessity of combination therapies rather single drug administration due to the quick resistance of the tumor to Palbociclib treatment.