CDK4/6 inhibition
CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models
... The CDK4/6 kinase complexes are a particularly compelling target in HER2 positive breast ...cancer. CDK4 and CDK6 are kinases that are activated by D-type cyclins ...Importantly, CDK4/6 ...
12
Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition
... for CDK4/6 activity for tumor maintenance in order to selectively radioprotect hematopoietic progenitors (Figure 4, E and F), thereby improving survival after IR without compromising tumor cell kill (Figure ...
10
Functional genomics identifies predictive markers and clinically actionable resistance mechanisms to CDK4/6 inhibition in bladder cancer
... against different key molecules in these pathways in breast cancer, myeloproliferative neoplasia, mucosal melanomas and leukemia overcame this resistance [18, 19, 53–55]. In particular, RTK/PI3K-Akt pathway inhibitors ...
14
Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer.
... to CDK4/6 inhibition were predominantly composed of actively proliferating CDK2 high cells, whereas TNBC cell lines sensitive to CDK4/6 inhibition were predominantly composed of ...
35
Defining the transcriptional and biological response to CDK4/6 inhibition in relation to ER+/HER2- breast cancer
... Mitogenic signals serve to both drive cell cycle progression and fuel cell growth/metabolism for subsequent cell division [32]. In fact, key genes involved in glucose (G6PD and PGM2L1) and glutamine (GLS) metabolism were ...
13
CDK4/6 inhibition enhances pulmonary inflammatory infiltration in bleomycin-induced lung fibrosis
... Data from our laboratory reinforces this need to care- fully evaluate pulmonary inflammatory side effects fol- lowing CDK4/6 inhibition. In a preclinical experimental setting we investigated whether ...
5
Specific CDK4/6 inhibition in breast cancer: a systematic review of current clinical evidence
... Particular attention has been paid to the search for potential biomarkers for efficacy of CDK 4/6 inhibitors. Increased expression of cyclin D and Rb protein was asso- ciated with response in vitro, as was ...
11
The anti-tumor efficacy of CDK4/6 inhibition is enhanced by the combination with PI3K/AKT/mTOR inhibitors through impairment of glucose metabolism in TNBC cells
... to CDK4/6 inhibition, is known to result in its activation; active Rb maintains E2F in a repressed state, with consequent inhibition of downstream gene transcription ...
12
CDK4/6 inhibition in low burden and extensive metastatic breast cancer: summary of an ESMO Open—Cancer Horizons pro and con discussion
... of CDK4/6 inhibi- tors, and further positive studies for OS will be reported ...of CDK4/6 inhibitors cannot conclusively be judged yet, and the optimal strategy for deploying them in clinical ...
8
Recent advances of highly selective CDK4/6 inhibitors in breast cancer
... the CDK4/6-RB-E2F pathway is pivotal to guiding the utilization of palbociclib treat- ...to CDK4/6 inhibition-induced cell cycle arrest, while overexpression of E2F was capable of ...
12
A novel tankyrase inhibitor, MSC2504877, enhances the effects of clinical CDK4/6 inhibitors.
... cycle blockade initiated by CDK4/6 inhibition, the addition of MSC2504877 suppressed these Cyclin D2/E2 responses (Figure 6C,D). We also noted a time dependent effect on the levels of phosphorylated ...
45
Elacestrant (RAD1901) exhibits anti tumor activity in multiple ER+ breast cancer models resistant to CDK4/6 inhibitors
... We evaluated inhibitors of the PI3K/mTOR pathway in several PDX models harboring PIK3CA mutations derived from patients treated with a combination of an AI and palbociclib (ST3932 and CTG-2308) or fulves- trant and ...
17
To Cycle or Fight-CDK4/6 Inhibitors at the Crossroads of Anticancer Immunity.
... 8. Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor- positive human ...
25
The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma
... resulting CDK4/6 hyperactivation are considered to be major oncogenic drivers ...of CDK4/6, inhibits cyclin D1 interaction with CDK4/6 and prevents phosphorylation of the RB ...
11
Selective impact of CDK4/6 suppression on patient-derived models of pancreatic cancer
... targeting CDK4/6, xenografts derived from established cell lines rapidly ...on CDK4/6 inhibition, cell cycle responses influence the activity of a range of targeted agents [42, 43], and ...
14
Treating cancer with selective CDK4/6 inhibitors.
... mTOR inhibition with CDK4/6 inhibitors (figure ...with CDK4 and with PI3K hyper-activation 131 , and CDK4/6 inhibition can overcome resistance to both PI3K ...
31
Functional, chemical genomic, and super-enhancer screening identify sensitivity to cyclin D1/CDK4 pathway inhibition in Ewing sarcoma
... of CDK4/6 inhibitors with conventional cytotoxics [48], which require cell cycling for efficacy, use of CDK4/6 inhibitors in combination with standard cytotoxic chemotherapy will likely ...
16
<p>Fulvestrant in Combination with CDK4/6 Inhibitors for HER2- Metastatic Breast Cancers: Current Perspectives</p>
... – CDK4/6 holoenzyme, and act to limit the pro- liferation of sensitive tumor ...cells, CDK4/6 inhibition nor- mally induces a phenotype reminiscent of cellular senescence, 8 consistent ...
12
Efficacy of CDK4 inhibition against sarcomas depends on their levels of CDK4 and p16ink4 mRNA
... of CDK4/6 to be tested and approved in humans for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive human epidermal growth factor receptor 2 ...
18
Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity
... Telomerase is a critical enzyme that serves an important functional role in a plethora of biological processes, ranging from organismal development and regeneration to chronological aging [1] and the onset of the ...
18