Therapy after cyclin‐dependent kinase inhibition in metastatic hormone receptor‐positive breast cancer: Resistance mechanisms and novel treatment strategies

Sharifi, Marina N.; Anandan, Apoorva; Grogan, Patrick T.; O’Regan, Ruth

doi:10.1002/cncr.32931

Cited by 19 publications

(16 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, prolonged treatment eventually provokes resistance, which has been attributed to the loss of the Rb tumor-suppressor or cyclin D1, activation of CDK2, cyclin E1 and amplification of CDK6 [104][105][106]. The identification of biomarkers predicting the responsiveness towards CDK4/6 inhibitors is of great importance [79,107]. Factors that might predict primary resistance were already assessed during early clinical trials of palbociclib.…”

Section: Resistance To Cdk4/6 Inhibitorsmentioning

confidence: 99%

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

2020

View full text Add to dashboard Cite

Despite the development of targeted therapies and novel inhibitors, cancer remains an undefeated disease. Resistance mechanisms arise quickly and alternative treatment options are urgently required, which may be partially met by drug combinations. Protein kinases as signaling switchboards are frequently deregulated in cancer and signify vulnerable nodes and potential therapeutic targets. We here focus on the cell cycle kinase CDK6 and on the MAPK pathway and on their interplay. We also provide an overview on clinical studies examining the effects of combinational treatments currently explored for several cancer types.

show abstract

Section: Resistance To Cdk4/6 Inhibitorsmentioning

confidence: 99%

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

2020

View full text Add to dashboard Cite

show abstract

“…The ESMO guideline recommended alpelisib plus endocrine therapy for patients with PIK3CA-mutated tumors or everolimus plus endocrine therapy for those with PIK3CA wild type or unknown tumors as the best subsequent treatment [2]. Furthermore, clinical trials examining the effect of PI3K inhibitors and AKT inhibitors on post-CDK4/6 inhibitors are now ongoing [25].…”

Section: Discussionmentioning

confidence: 99%

Treatment Strategy for Patients with HR-Positive HER2-Negative Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitors

et al. 2021

View full text Add to dashboard Cite

Background/Aims: The study aim was to evaluate if mTOR inhibitors can be considered as a treatment option for HR+ HER2− metastatic breast cancer (MBC) after progression on CDK4/6 inhibitors in clinical practice. Methods: We retrospectively collected the clinicopathological data of patients with HR+ HER2− MBC treated with CDK4/6 inhibitors and subsequent therapies at our institution between 2014 and 2020. The patients were divided into 3 groups according to the type of subsequent treatment: (A) exemestane plus everolimus, (B) endocrine monotherapy, and (C) chemotherapy. Overall survival (OS) was estimated by using the Kaplan-Meier method and compared by using the log-rank test. The efficacy and adverse events (AEs) of each subsequent treatment were assessed by using Fisher’s exact tests. Results: Eighty-six patients (34 in group A, 20 in group B, 32 in group C) were included. The most common endocrine therapy in group B was fulvestrant (40%). The major chemotherapy regimen in group C was eribulin (25%). The median OS times after stopping CDK4/6 inhibitors were 34.5 months (95% confidence interval, 17.2 to NA), 13.6 months (3.9 to NA), and 19.5 months (18.8 to NA) in group A, group B, and group C, respectively. The only significant difference in OS was observed between group A and group B (20.9 months; p = 0.003). There was no difference in the incidence of grade 3 AEs between groups A and C or in the frequency of treatment discontinuation because of AEs among the 3 groups. Conclusion: Our study shows that mTOR inhibitors might be an effective treatment option for patients with HR+ HER2− MBC previously treated with CDK4/6 inhibitors.

show abstract

“…Still, the question remains how to treat patients that progress under CDK4/6 inhibition. Novel strategies include, among others, the continuation of CDK4/6 inhibitors through progression as well as triple combinations with PI3K or checkpoint inhibitors [ 81 ].…”

Section: Modern Approaches In Advanced Breast Cancermentioning

confidence: 99%

Endocrine Treatment for Breast Cancer Patients Revisited—History, Standard of Care, and Possibilities of Improvement

Nabieva

Fasching

2021

Cancers

View full text Add to dashboard Cite

Purpose of review: Due to the findings of current studies and the approval of novel substances for the therapy of hormone-receptor-positive breast cancer patients, the established standards of endocrine treatment are changing. The purpose of this review is to give an overview of the history of endocrine treatment, to clarify its role in the present standard of care, and to discuss the possibilities of improvement. Recent findings: Tamoxifen, aromatase inhibitors, and fulvestrant are the main drugs that have been used for decades in the therapy of hormone-receptor-positive breast cancer patients. However, since a relevant number of women suffer at some point from disease recurrence or progression, several novel substances are being investigated to overcome resistance mechanisms by interfering with certain signaling pathways, such as the PI3K/AKT/mTOR or the CDK4/6 pathways. mTOR and CDK4/6 inhibitors were the first drugs approved for this purpose and many more are in development. Summary: Endocrine treatment is one of the best tolerable cancer therapies available. Continuous investigation serves to improve patients’ outcomes and modernize the current standard of care. Considering the resistance mechanisms and substances analyzed against these, endocrine treatment of hormone-receptor-positive breast cancer is on the brink of a new era.

show abstract

Therapy after cyclin‐dependent kinase inhibition in metastatic hormone receptor‐positive breast cancer: Resistance mechanisms and novel treatment strategies

Cited by 19 publications

References 67 publications

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

Treatment Strategy for Patients with HR-Positive HER2-Negative Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitors

Endocrine Treatment for Breast Cancer Patients Revisited—History, Standard of Care, and Possibilities of Improvement

Contact Info

Product

Resources

About