Cell-based assays for CDK8/19 inhibition are not easily defined, since there are no known cellular functions unique to these kinases. To solve this problem, we generated derivatives of 293 cells with CRISPR knockout of one or both of CDK8 and CDK19....
Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer....
Uncontrolled proliferation is the hallmark of cancer and other proliferative disorders and abnormal cell cycle regulation is, therefore, common in these diseases. Cyclin-dependent kinases (CDKs) play a crucial role in the control of the cell cycle a...
CDK4/6 inhibitors exert effective anti-tumor effects by blocking the cell cycle and, as a result, have become vital in the systemic treatment of malignant tumors. Previous research has indicated that CDK4/6 inhibitors not only exert effects on the ce...
Breast cancer (BC) is the most common cause of cancer-related death in women worldwide. Therapies targeting molecular pathways altered in BC had significantly enhanced treatment options for BC over the last decades, which ultimately improved the live...
Background: Treatment with aromatase inhibitors (AIs) is fundamental in women with hormone receptor-positive breast cancer in the adjuvant as well as the metastatic setting. Even though it is considered to be a well-tolerated therapy, aromatase inhib...
Background: Aromatase inhibitors (AIs) are associated with musculoskeletal pain in one third (20–47%) of breast cancer patients. Recently, CDK4/6 inhibitors have emerged as a new therapeutic approach in hormone receptor (HR)-positive breast cancer. W...
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have emerged as novel treatment options in the management of advanced or metastatic breast cancer. MicroRNAs are endogenous non-coding 19–22-nucleotide-long RNAs that regulate gene expression in develop...
Inflammation is a crucial pathological feature in cancers and kidney diseases, playing a significant role in disease progression. Cyclin-dependent kinases CDK4 and CDK6 not only contribute to cell cycle progression but also participate in cell metabo...
Deregulation of cell cycle, via cyclin D/CDK/pRb pathway, is frequently observed in breast cancer lending support to the development of drugs targeting the cell cycle control machinery, like the inhibitors of the cycline-dependent kinases (CDK) 4 and...
Guidelines for the first-line treatment of Hormone Receptor-positive, HER2-negative advanced or recurrent breast cancer have shifted to combination therapies of a CDK4/6 inhibitor and endocrine therapy. However, determining an optimal subsequent ther...
Objective: We aimed to evaluate the use of CDK4/6 inhibitors as a risk factor for medication-related osteonecrosis of the jaw (MRONJ) in a cohort of patients with metastatic breast cancer treated with denosumab. Methods: This was a multicentre, retro...
Type II testicular germ cell tumors (TGCT) are the most frequently diagnosed solid malignancy in young men. Up to 15% of patients with metastatic non-seminomas show cisplatin resistance and a very poor survival rate due to lacking treatment options....
The latest and newest discoveries for advanced and metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer are the three cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) in associati...
Estrogen receptor-positive (ER+) breast cancer is the most common form of breast cancer. Antiestrogens were the first therapy aimed at treating this subtype, but resistance to these warranted the development of a new treatment option. CDK4/6 inhibito...
CDK4/6 inhibitors in association with endocrine therapy represent the best therapeutic choice for either endocrine-sensitive or resistant hormone-receptor-positive advanced breast cancer patients. On the contrary, the optimal therapeutic strategy aft...
CDK4/6 and aromatase are prominent targets for breast cancer drug discovery and are involved in abnormal cell proliferation and growth. Although aromatase inhibitors have proven to be effective (for example exemestane, anastrozole, letrozole), resist...
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are approved for the treatment of human epidermal growth factor receptor 2 (HER-2)-negative, hormone receptor-positive breast cancer. The cardiovascular toxicity of CDK4/6 inhibitors is not well und...
CDK4/6 inhibition represents a new generation of cancer therapies, targeting CDK4/6 complexes to induce cell cycle arrest in the G1 phase. These inhibitors have been widely used in combination with hormone receptor antagonists for treating ER+/HER2&m...
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and endocrine therapy are the gold standards for systemic therapy for patients with hormone-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer. Followi...
Existing treatment strategies for pancreatobiliary malignancies are limited. Nowadays, surgery is the only path to cure these types of cancer, but only a small number of patients present with resectable tumors at the time of diagnosis. The notoriousl...
Cyclin-dependent kinase 2 (CDK2) has been garnering considerable interest as a target to develop new cancer treatments and to ameliorate resistance to CDK4/6 inhibitors. However, a selective CDK2 inhibitor has yet to be clinically approved. With the...
Background. To date, a number of human pathogenic viruses are still unaddressed by the current repertoire of approved antiviral drugs. In order to widen this spectrum of preventive measures against virus infections, we have focused on additional host...
New evidence on the impact of dysregulation of the CDK4/6 pathway on breast cancer (BC) cell proliferation has led to the development of selective CDK4/6 inhibitors, which have radically changed the management of advanced BC. Despite the improved out...
Purpose of review: Tamoxifen and aromatase inhibitors can be considered as some of the first targeted therapies. For the past 30 years, they were the endocrine treatment standard in the advanced and early breast cancer setting. CDK4/6 inhibitors, how...
The approval of cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) has remarkably improved the survival outcomes of patients with advanced hormone receptor-positive (HR+) breast cancer (BC), becoming the n...
Background: CDK4/6 inhibitors (CDK4/6i) combined with hormone therapies have demonstrated clinical benefit in HR+, HER2- breast cancer patients. However, the onset of resistance remains a concern and highlights a need for therapeutic strategies to im...
Over the last decade, CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) have emerged as promising anticancer drugs. Numerous studies have demonstrated that CDK4/6 inhibitors efficiently block the pRb-E2F pathway and induce cell cycle arrest...
Front-line therapy for advanced and metastatic hormone receptor positive (HR+), HER2 negative (HER−) advanced or metastatic breast cancer (mBC) is endocrine therapy with a CDK4/6 inhibitor (CDK4/6i). The introduction of CDK4/6i has dramatically...
CDK 4/6 inhibitors have demonstrated significant improved survival for patients with estrogen receptor (ER) positive breast cancer (BC). However, the ability of these promising agents to inhibit bone metastasis from either ER+ve or triple negative BC...
Treatment paradigms in advanced hormone receptor (HR)-positive breast cancer were substantially transformed with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) approval. The addition of these drugs to endocrine treatment profoundly improved pro...
Purpose: CDK4/6 inhibitors require meticulous monitoring due to their potential to cause hematological toxicities and hepatotoxicity. This study evaluates the safety of combining CDK4/6 inhibitors with palliative radiotherapy in patients with metasta...
Pharmacotherapy of acute myeloid leukemia (AML) remains challenging, and the disease has one of the lowest curability rates among hematological malignancies. The therapy outcomes are often compromised by the existence of a resistant AML phenotype ass...
Cyclin-dependent kinases (CDKs) are generally involved in the progression of cell cycle and cell division in normal cells, while abnormal activations of CDKs are deemed to be a driving force for accelerating cell proliferation and tumorigenesis. Ther...
CDK4/6 inhibitors (CDK4/6i) are recommended in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC). Up to now, no prognostic biomarkers have been identified in this setting. We retrospectively analyzed the expres...
The introduction in clinical practice of selective cyclin-dependent kinase (CDK) 4/6 inhibitors improves the outcome of patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mB...
The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has becom...
Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly improved progression-free survival in hormone-receptor-positive (HR+), human-epidermal-growth-factor-receptor-type-2-negative (HER2−) metastatic luminal breast cancer (mLBC). Sever...
Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been developed and clinically used as a frontline targeted therapeutic agent for hormone receptor-positive (HR+), HER2-negative breast cancer. However, the efficacy for CDK4/6 inhibitor...
In recent years, three PARP inhibitors and three CDK4/6 inhibitors have been approved by the FDA for the treatment of recurrent ovarian cancer and advanced ER-positive breast cancer, respectively. However, the clinical benefits of the PARPi or CDK4/6...
Osimertinib is a third-generation epidermal growth factor receptor and tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of lung adenocarcinoma patients harboring EGFR mutations. However, acquired resistance to this targeted therapy is...
Background: CDK4/6-inhibitors have demonstrated similar efficacy and are considered an effective first-line endocrine treatment of patients with hormone-receptor positive (HR+)/human-epidermal-growth-factor-receptor-2 negative (HER2−) metastati...
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard of care for HR-positive/HER2-negative advanced breast cancer patients. However, their role in the treatment of brain metastases is currently unclear. We...
A metastatic state of breast cancer (MBC) affects hundreds of thousands of women worldwide. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) MBC, cyclin-dependent kinase (CDK)4/6 inhibitors can improv...
Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors...
The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with ra...
CDK4/6 inhibitors (CDK4/6i) and endocrine therapy are the standard treatment for patients with hormone receptor-positive and HER2 negative (HR+/HER2−) metastatic breast cancer. Patients might show intrinsic and acquired resistance, which leads to tre...
Background: The treatment of hormone receptor positive (HR+), HER-2 negative metastatic breast cancer (MBC) has radically changed over the last few years. CDK4/6 inhibitors combined with endocrine therapy have become the standard of care as a front-l...
Background and Objectives: Bone metastases in patients can cause significant quality-of-life declines due to skeletal-related events (SREs). SRE is defined as the occurrence of radiotherapy for bone pain, pathologic fracture, bone surgery, spinal cor...
Cyclin-dependent kinase 4/6 inhibitors are the standard of care for hormone receptor-positive metastatic breast cancer. This retrospective study reports on genomic biomarkers of CDK 4/6i resistance utilizing genomic data acquired through routine clin...
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