Nature Cancer, Год журнала: 2025, Номер 6(1), С. 24 - 40
Опубликована: Янв. 30, 2025
Язык: Английский
Drugs, Год журнала: 2025, Номер unknown
Опубликована: Янв. 17, 2025
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2−) metastatic breast cancer, and are now also established agents in high-risk intermediate-risk HR+ early cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression been successfully evaluated setting, considered a standard care. Mechanism action resistance mechanisms against addition to endocrine represent an important research topic, for Clinically, efficient substances that usually well tolerated. However, side effects differing between reported, might lead discontinuation, including disease setting. In adjuvant palbociclib has not improved outcomes, whereas large randomized phase III trials demonstrated significant disease-free survival benefit ribociclib (NATALEE trial) abemaciclib (monarchE trial). Patient selection, duration, backbone therapy, other study details differ these pivotal trials. This review focuses on both scientific background as all available clinical data CDK4/6i, with particular emphasis their use
Язык: Английский
Процитировано
1
Cancer Drug Resistance, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
This review offers an expert perspective on biomarkers, CDK4/6 inhibitor efficacy, and therapeutic approaches for managing hormone receptor-positive (HR+), human epidermal growth factor receptor-negative (HER2-) advanced breast cancer (ABC), particularly after progression. Key trials have demonstrated that combining inhibitors with endocrine therapy (ET) significantly improves progression-free survival (PFS), median durations ranging from 14.8 to 26.7 months, overall (OS), reaching up 53.7 months. Actionable such as PIK3CA ESR1 mutations, emerged pivotal tools guide second-line treatment decisions, enabling the use of targeted therapies like alpelisib elacestrant emphasizing important role biomarkers in guiding selection therapy. overview aims provide clinicians a practical up-to-date framework inform decisions improve patient care context this challenging disease. Additionally, we emerging novel strategies address difficult clinical landscape.
Язык: Английский
Процитировано
1
Опубликована: Янв. 28, 2025
The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy has revolutionized treatment for hormone receptor-positive (HR+) metastatic breast cancer. However, the emergence resistance in most patients often leads to discontinuation with no consensus on effective second-line therapies. therapeutic benefits maintaining CDK4/6i or incorporating CDK2 (CDK2i) after disease progression remain unclear. Here, we demonstrate that sustained therapy, either alone combined CDK2i, significantly suppresses growth drug-resistant HR + Continued induces a non-canonical pathway retinoblastoma protein (Rb) inactivation via post-translational degradation, resulting diminished E2F activity delayed G1 progression. Importantly, our data highlight CDK2i should be effectively suppress overcome resistance. We also identify cyclin E overexpression as key driver inhibition. These findings provide crucial insights into overcoming cancer, supporting continued use strategic incorporation improve outcomes.
Язык: Английский
Процитировано
1
The Lancet Oncology, Год журнала: 2025, Номер 26(3), С. 343 - 354
Опубликована: Фев. 17, 2025
Язык: Английский
Процитировано
1
Cancer Letters, Год журнала: 2024, Номер 588, С. 216747 - 216747
Опубликована: Фев. 23, 2024
Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) have rapidly received Food Drug Administration (FDA) approval as a new type of therapy for patients with advanced hormone receptor-positive breast cancer. However, the widespread application CDK4/6i, drug resistance has become challenge clinical practice greatly limited treatment effect. Here, whole microenvironment landscape ER
Язык: Английский
Процитировано
7
Breast Cancer Research and Treatment, Год журнала: 2024, Номер 206(3), С. 551 - 559
Опубликована: Май 4, 2024
Язык: Английский
Процитировано
7
Breast Care, Год журнала: 2024, Номер 19(3), С. 183 - 191
Опубликована: Янв. 1, 2024
The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents 2024 update evidence-based recommendations for diagnosis and treatment patients with locally advanced metastatic breast cancer.
Язык: Английский
Процитировано
6
Endocrinology, Год журнала: 2024, Номер 165(6)
Опубликована: Апрель 21, 2024
Abstract Annual breast cancer (BCa) deaths have declined since its apex in 1989 concomitant with widespread adoption of hormone therapies that target estrogen receptor alpha (ERα), the prominent nuclear expressed ∼80% BCa. However, up to ∼50% patients who are ER+ high-risk disease experience post endocrine therapy relapse and metastasis distant organs. The vast majority BCa mortality occurs this setting, highlighting inadequacy current therapies. Genomic abnormalities ESR1, gene encoding ERα, emerge under prolonged selective pressure enable resistance. These genetic lesions include focal amplifications, hotspot missense mutations ligand binding domain, truncations, fusions, complex interactions other receptors. Tumor cells utilize aberrant ERα activity proliferate, spread, evade as well cancers. Cutting edge studies on structural transcriptional relationships being harnessed produce new shown benefits ESR1 mutations. In review we discuss history research unlocking unknown aspects signaling including basis for antagonism, future directions investigation. addition, development from their inception present day survey avenues drug improve pharmaceutical profiles, targeting, efficacy.
Язык: Английский
Процитировано
6
Current Oncology Reports, Год журнала: 2024, Номер 26(6), С. 665 - 678
Опубликована: Май 7, 2024
Язык: Английский
Процитировано
5
JNCI Cancer Spectrum, Год журнала: 2023, Номер 7(4)
Опубликована: Июнь 26, 2023
The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors palbociclib, ribociclib, abemaciclib are standard-of-care therapy for hormone receptor-positive advanced or metastatic breast cancer, based on randomized trials showing improved progression-free survival all 3 drugs overall ribociclib abemaciclib. Results in early cancer discordant, with sustained improvement invasive disease-free demonstrated but not other CDK4/6 to date. We review nonclinical studies exploring mechanistic differences between the drugs, impact of continuous dosing treatment effect, translational research into potential resistance mechanisms prognostic predictive markers. focus particularly how emerging findings may help us understand similarities available inhibitors. Even at late-stage clinical development, there remains much learn about agents this class exert their varying effects.
Язык: Английский
Процитировано
11