CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib

Eggersmann, Tanja K.; Degenhardt, Tom; Gluz, Oleg; Wuerstlein, Rachel; Harbeck, Nadia

doi:10.1007/s40259-019-00337-6

Cited by 77 publications

(48 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[34][35][36][37][38][39] Numerous studies have shown that CDK4/6 inhibitors have many other antitumor effects besides cell cycle inhibition. [40][41][42][43] However, although they can eliminate tumors through multiple mechanisms, CDK4/6 inhibitors are not effective for all patients. Acquired and intrinsic drug resistance greatly limits their efficacy.…”

Section: Discussionmentioning

confidence: 99%

HMGB1 is a key factor for tamoxifen resistance and has the potential to predict the efficacy of CDK4/6 inhibitors in breast cancer

Zhang

Wang

et al. 2021

Cancer Science

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

HMGB1 is a key factor for tamoxifen resistance and has the potential to predict the efficacy of CDK4/6 inhibitors in breast cancer

Zhang

Wang

et al. 2021

Cancer Science

View full text Add to dashboard Cite

show abstract

“…In the NEMO study, pneumonitis occurred in 1% of the patients treated by binimetinib and a decrease of the left ejection fraction in 4% of the patients (2). In contrast, neither a decrease in left ventricular ejection fraction nor pneumonitis was observed with CDK4/6 inhibitors (13,14). Therefore we decided to re-start CDK4/6 inhibition earlier than MEK inhibiton.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Combined CDK4/6 and MEK Inhibition in Refractory CDKN2A and NRAS Mutant Melanoma

et al. 2021

View full text Add to dashboard Cite

There are only limited treatment options for metastatic NRAS mutant melanoma patients with resistance to immune checkpoint inhibitors. Besides activation of the mitogen-activated protein (MAP) kinase pathway, they often have additional disturbances in cell cycle regulation. However, unlike BRAF mutant melanoma, no targeted therapy has yet been approved for NRAS mutant melanoma so far. Here we present a NRAS mutant melanoma patient with response to combined binimetinib and ribociclib therapy following characterization of the molecular defects of the tumor by panel sequencing. Next generation sequencing (708 cancer genes) of a soft tissue metastasis revealed a homozygous deletion of CDKN2A in addition to the previously known NRAS mutation, as well as amplification of CCNE1 and CDK6. Immunohistochemical staining of the altered cell cycle genes confirmed loss of p16, reduced expression of p21 and high expression of CDK6 and cyclin D1. As the patient had been progressive on combined immunotherapy, targeted therapy with combined MEK and CDK4/6 inhibition was initiated as recommended by the molecular tumor board. Response to treatment was monitored with PET/CT and liquid biopsy, serum LDH, and S100. In addition, a patient-derived xenograft (PDX) was used to prove the efficacy of the two drugs in combination. Furthermore, senescence-associated beta-galactosidase staining showed that more cells were senescent under the combination treatment of binimetinib and ribociclib. Our case demonstrates how an individualized, molecular-based therapeutic approach could be found based on next-generation sequencing results. Furthermore our report highlights the fruitful and efficient collaboration of dermatooncologists, human geneticists, molecular pathologists, biochemists, radiologists, and nuclear physicians. Further studies are urgently needed to expand the very limited therapeutic landscape of NRAS mutated melanoma.

show abstract

“…A recent review (Yu et al, 2020) described some novel potential targets such as gene targets, Noncoding RNA, classical signaling pathways among others. From a clinical point of view, in 2017 the Food and Drug Administration (FDA) approved the use of cyclin-dependent kinases 4/6 (CDK4/6) inhibitors (ribociclib, palbociclib, abemaciclib) for ER+ and HER2-advanced BC (Eggersmann et al, 2019). In the following year, also PARP inhibitors (talazoparib, olaparib) were approved for HER2-and BRCA1/2-mutant advanced BC (McCann and Hurvitz, 2018).…”

Section: Tnbc Treatmentmentioning

confidence: 99%

Focus on Triple-Negative Breast Cancer: Potassium Channel Expression and Clinical Correlates

Lastraioli

2020

Front. Pharmacol.

View full text Add to dashboard Cite

Despite improvements in early diagnosis and treatment, breast cancer is still a major health problem worldwide. Among breast cancer subtypes, the most challenging and harder to treat is represented by triple-negative molecular subtype. Due to its intrinsic features this subtype cannot be treated neither with hormonal therapy (since it does not express estrogen or progesterone receptors) nor with epidermal growth factor receptor 2 (HER2) inhibitors (as it does not express high levels of this protein). For these reasons, the standard of care for these patients is represented by a combination of surgery, radiation therapy and chemotherapy. In this scenario, searching for novel biomarkers that might help both in diagnosis and therapy is mandatory. In the last years, it was shown that different families of potassium channels are overexpressed in primary breast cancers. The altered ion channel expression may be useful for diagnostic and therapeutic purposes due to some peculiar characteristics of this class of molecules. Ion channels are defined as pore-forming transmembrane proteins regulating passive ion fluxes in the cells. Ion channels represent good potential markers since, being localized at the plasma membrane level, their detection and block with specific drugs and antibodies might be fast and tunable. This review focuses on triple-negative breast cancers and recapitulates the current knowledge about potassium channels' clinical relevance and their potential use in the clinical setting, for triple-negative breast cancer diagnosis and therapy.

show abstract

CDK4/6 Inhibitors Expand the Therapeutic Options in Breast Cancer: Palbociclib, Ribociclib and Abemaciclib

Cited by 77 publications

References 31 publications

HMGB1 is a key factor for tamoxifen resistance and has the potential to predict the efficacy of CDK4/6 inhibitors in breast cancer

HMGB1 is a key factor for tamoxifen resistance and has the potential to predict the efficacy of CDK4/6 inhibitors in breast cancer

Case Report: Combined CDK4/6 and MEK Inhibition in Refractory CDKN2A and NRAS Mutant Melanoma

Focus on Triple-Negative Breast Cancer: Potassium Channel Expression and Clinical Correlates

Contact Info

Product

Resources

About