CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective

Zhou, Fiona H.; Downton, Teesha; Freelander, Allegra; Hurwitz, Joshua; Caldon, C. Elizabeth; Lim, Elgene

doi:10.3389/fcell.2023.1148792

Cited by 14 publications

(8 citation statements)

References 129 publications

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“…39 Increasing evidence suggests that CDK4/6I resistance can result from RB1 inactivation; CDK6, CCNE1/2, and aurora kinase A overexpression; and mutational activation of FGFR, ERBB2, AKT1, and RAS oncogenes. 40,41 The PALOMA-3 trial (ClinicalTrials.gov identifier NCT01942135) revealed that acquired ERBB2 mutations contribute to CDK4/6i resistance. 42 These mutations can enhance HER2 pathway signaling and sensitize tumors to HER2 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Real‐world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis

Liang,

Zhang,

Gui

et al. 2024

Cancer

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BackgroundCyclin‐dependent kinase 4/6 inhibitors combined with endocrine therapy (ET) comprise the standard treatment for patients with hormone receptor‐positive and human epidermal growth factor 2 (HER2)‐negative metastatic breast cancer. The optimal systematic treatment after progression on palbociclib and the role of HER2 expression among these patients remain unclear.MethodsThe authors retrospectively identified 361 patients who received palbociclib combined with ET. Progression‐free survival (PFS) and overall survival (OS) were analyzed based on subsequent treatments and HER2 status (PFSsub and OSsub, respectively). PFS1 and OS1 were calculated from palbociclib administration to disease progression/death and death from any cause, respectively. PFSsub and OSsub were calculated from subsequent treatment initiation.ResultsThe median PFS1 and OS1 were 10.2 and 39.9 months, respectively. The median PFSsub and OSsub of 111 patients (54.7%) who received chemotherapy were 4.9 months and 20.0 months, respectively, whereas those of 89 patients (43.8%) who received endocrine backbone therapy were 5.9 months and 29.3 months, respectively. Among them, 31 patients (15.3%) who received abemaciclib combined with new ET showed better PFSsub and OSsub (12.2 months and not reached, respectively). The median PFS1 was significantly shorter in the HER2‐low subgroup than in the HER2‐zero subgroup among patients who received second‐line or later palbociclib (6.1 vs. 7.8 months; p = .040) but did not differ among patients who received first‐line palbociclib.ConclusionsVarious regimens after palbociclib use were received. An improvement was noted in PFS among patients who received endocrine backbone therapy relative to chemotherapy, which may have been secondary to the receipt of chemotherapy by patients with more aggressive disease. HER2 status was not related to the effect of first‐line palbociclib, but it may play a role in later lines.

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Section: Discussionmentioning

confidence: 99%

Real‐world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis

Liang,

Zhang,

Gui

et al. 2024

Cancer

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“…Increasing evidence suggests that the hepatocyte growth factor/mesenchymal-epithelial transition factor (c-MET) signaling pathway serves a key role in carcinogenesis, regulation of tumor microenvironment, metastasis and drug resistance (58,59). Aberrations in c-MET have been described among several potential mechanisms of resistance to CDK4/6is (60). Increased c-MET expression, frequently observed in HR + /HER2breast cancer (61,62), is associated with disease stage, progesterone receptor levels, Ki67 index and worse survival (63).…”

Section: Discussionmentioning

confidence: 99%

Liquid biopsy utilizing miRNA in patients with advanced breast cancer treated with cyclin‑dependent kinase 4/6 inhibitors

Kubeczko,

Tudrej,

Tyszkiewicz

et al. 2024

Oncol Lett

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Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are the mainstay of treatment of hormone receptor + /human epidermal growth factor receptor 2-patients with advanced breast cancer (ABC). Despite improvements in overall survival, most patients experience disease progression. Biomarkers derived from a liquid biopsy are appealing for their potential to detect resistance to treatment earlier than computed tomography imaging. However, clinical data concerning microRNAs (miRNAs/miRs) in the context of CDK4/6is are lacking. Thus, the present study assessed the use of miRNAs in patients with ABC treated with CDK4/6is. Patients treated for ABC with CDK4/6is between June and August 2022 were eligible. miRNA expression analyses were performed using a TaqMan™ low-density miRNA array. A total of 80 consecutive patients with ABC treated with CDK4/6is at Maria Sklodowska-Curie National Research Institute of Oncology (Gliwice, Poland) were assessed, with 14 patients diagnosed with progressive disease at the time of sampling, 55 patients exhibited clinical benefit from CDK4/6i treatment and 11 patients were at the beginning of CDK4/6i treatment. Patients with disease progression had significantly higher levels of miR-21 (P=0.027), miR-34a (P=0.011), miR-193b (P=0.032), miR-200a (P=0.027) and miR-200b (P=0.003) compared with patients who benefitted from CDK4/6i treatment. Significantly higher levels of miR-34a expression were observed in patients with progressive disease than in patients beginning treatment (P=0.031). The present study demonstrated the potential innovative role of circulating miRNAs during CDK4/6i treatment. Plasma-based expression of miR-21, -34a, -193b, -200a and -200b effectively distinguished patients with ABC who responded to CDK4/6i treatment from patients who were resistant. However, longitudinal studies are required to verify the predictive and prognostic potential of miRNA.

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“…In melanoma, multiple mutations can affect CDK4/6 activity and increase proliferation by promoting the G1-S transition [53]. Interestingly, CDK4/6 can be activated beyond the MAPK pathway via the estrogen receptor (ER) signaling pathway, which is common in breast cancer [54,55]. Because CDK4/6 inhibitors have already been developed and effectively used to treat breast cancer tumors, clinicians are testing the efficacy of CDK4/6 inhibitors in combination with other inhibitors to combat melanoma.…”

Section: Non-braf and Mek-related Biomarkersmentioning

confidence: 99%

Development of Personalized Strategies for Precisely Battling Malignant Melanoma

Isaak,

Clements,

Buenaventura

et al. 2024

IJMS

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Melanoma is the most severe and fatal form of skin cancer, resulting from multiple gene mutations with high intra-tumor and inter-tumor molecular heterogeneity. Treatment options for patients whose disease has progressed beyond the ability for surgical resection rely on currently accepted standard therapies, notably immune checkpoint inhibitors and targeted therapies. Acquired resistance to these therapies and treatment-associated toxicity necessitate exploring novel strategies, especially those that can be personalized for specific patients and/or populations. Here, we review the current landscape and progress of standard therapies and explore what personalized oncology techniques may entail in the scope of melanoma. Our purpose is to provide an up-to-date summary of the tools at our disposal that work to circumvent the common barriers faced when battling melanoma.

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CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective

Cited by 14 publications

References 129 publications

Real‐world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis

Real‐world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis

Liquid biopsy utilizing miRNA in patients with advanced breast cancer treated with cyclin‑dependent kinase 4/6 inhibitors

Development of Personalized Strategies for Precisely Battling Malignant Melanoma

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