A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer

Bi̇lgi̇n, Burak; Şendur, Mehmet Ali Nahit; Dede, Didem Şener; Akıncı, Muhammed Bülent; Yalçın, Bülent

doi:10.1080/03007995.2017.1348344

Cited by 40 publications

(27 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The second of our key proteins, mitotic kinase CDK1, is known to accelerate critical processes required for mitosis (Enserink and Kolodner, 2010) and correlates with tumour grade (Chae et al, 2011). Moreover, inhibitors of the family members CDK4/6 have been FDA-approved for the treatment of metastatic breast cancer in a first-line setting (Bilgin et al, 2017). In conclusion, although this is a pilot discovery study and follow-ups with larger patient cohorts are required to further train and validate our classifier, our findings suggest that both INPP4B and CDK1 are promising alternative targets for anti-cancer therapy, as they exhibit similar level of association with ER status and tumour grade as ERBB2 with HER2 status, which is already successfully targeted to treat HER2 + breast cancer patients.…”

Section: Biological Relevance Of the Key Proteins Selected By The Decmentioning

confidence: 99%

Breast cancer classification based on proteotypes obtained by SWATH mass spectrometry

Bouchal

Schubert

Faktor

et al. 2019

Preprint

View full text Add to dashboard Cite

Accurate breast cancer classification is vital for patient management decisions, and better tumour classification is expected to enable more precise and eventually personalized treatment to improve patient outcomes. Here, we present a novel quantitative proteotyping approach based on SWATH mass spectrometry and establish key proteins for breast tumour classification derived from proteotype data. The study was based on 96 tissue samples representing five breast cancer subtypes according to conventional classification. Correlation of SWATH proteotype patterns indicated groups that largely recapitulate these subtypes. However, 2 the proteotype-based classification also revealed varying degrees of heterogeneity within the conventional subtypes, with triple negative tumours being the most heterogeneous. Proteins that contributed most strongly to the proteotype-based classification include INPP4B, CDK1, and ERBB2, which are associated with oestrogen receptor status, tumour grade, and HER2 status, respectively. While these three key proteins exhibited high levels of correlation between protein and transcript levels (R>0.67), general correlation did not exceed R=0.29, indicating the value of protein-level measurements of biomarkers and disease-regulated genes. Overall, our data shows how large-scale protein-level measurements by next-generation proteomics can lead to improved patient stratification for precision medicine.

show abstract

Section: Biological Relevance Of the Key Proteins Selected By The Decmentioning

confidence: 99%

Breast cancer classification based on proteotypes obtained by SWATH mass spectrometry

Bouchal

Schubert

Faktor

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In February 2015, however, the Food and Drug Administration (FDA) approved palbociclib as an initial endocrine-based therapy in combination with letrozole in postmenopausal women with HMR-positive, Her2-negative advanced breast cancer (64). Palbociclib is also effective in HR-positive metastatic breast cancer patients with fulvestrant (4).…”

Section: Breast Cancermentioning

confidence: 99%

“…1), overcame the disadvantages of the first generation of CDK4/6 inhibitors, showing promising anticancer effects and manageable toxicity. Of these three drugs, palbociclib and ribociclib have recently been approved by the Food and Drug Administration (FDA) as a new treatment strategy in combination with letrozole for hormone receptor (HR)-positive, advanced-stage breast cancer, showing promising results for these patients (4). Additionally, palbociclib has been successfully applied in multiple myeloma therapy.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review)

Liu

Chen

2018

Oncol Rep

View full text Add to dashboard Cite

An uncontrolled cell cycle is an obvious marker of tumor cells. The G1‑S phase is an important restriction point in the normal cell cycle, but in cancer cells the restriction function is reduced, leading to uncontrolled cell proliferation. Two cyclin‑dependent kinases (CDKs), CDK4 and CDK6, play a crucial role in the G1‑S phase transition. Inhibitors of CDK4/6 are presently the subjects of numerous studies, and PD 0332991, an inhibitor of CDK4/6, has been used to treat hormone receptor (HR)‑positive, advanced‑stage breast cancer. This inhibitor has also been studied in other cancers, such as lung cancer. In this review, we will discuss the regulation of the normal cell cycle transition from G1 to S phase, the most promising inhibitor of CDK4/6, PD 0332991, as applied in different cancers, and finally we propose a mechanism of acquired resistance as well as the incredible potential for CDK4/6 inhibitors in the treatment of cancer. Briefly, we assert that, going forward, a new treatment pattern for cancer may be a combination therapy with a cell cycle inhibitor and a molecular targeted drug.

show abstract

“…Several potent, selective inhibitors targeting CDK4/6 (CDK4/6is) have undergone clinical trials including palbociclib (PD0332991), abemaciclib (LY-2835219) and ribociclib (LEE001) [6,7], and have gained regulatory approval in combination with hormonal therapy in breast cancer [8][9][10][11]. However, evidence for clinical benefit has not been extended to other cancer types thus far, and relapse under therapy is frequent in the approved indication in breast cancer [9].…”

Section: Introductionmentioning

confidence: 99%

Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases

Zhang

Stockwell

Elbanna

et al. 2019

Preprint

View full text Add to dashboard Cite

Deregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer yet inhibitors against these kinases currently show use in restricted tumour contexts. The extent to which cancers depend on CDK4/6 and what may undermine such dependency is poorly understood. Here we report that signalling engaging the MET proto-oncogene receptor tyrosine kinase/focal adhesion kinase (FAK) axis leads to CDK4/6-independent CDK2-activation, involving as a critical mechanistic events loss of the CDK inhibitor p21 CIP1 and gain of its regulator, the ubiquitin ligase subunit SKP2. Combined inhibition of MET/FAK and CDK4/6 eliminates proliferation capacity of cancer cells in culture, and enhances tumour growth inhibition in vivo. Activation of the MET/FAK axis is known to arise through cancer extrinsic and intrinsic cues. Our work predicts that such cues support cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases and identifies MET/FAK as a tractable route to broaden the utility of CDK4/6 inhibitor-based therapies in the clinic. PalbociclibCrizotinib Absorbance, relative to vehicle control Cells seeded

show abstract

A current and comprehensive review of cyclin-dependent kinase inhibitors for the treatment of metastatic breast cancer

Cited by 40 publications

References 52 publications

Breast cancer classification based on proteotypes obtained by SWATH mass spectrometry

Breast cancer classification based on proteotypes obtained by SWATH mass spectrometry

Mechanisms of the CDK4/6 inhibitor palbociclib (PD 0332991) and its future application in cancer treatment (Review)

Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases

Contact Info

Product

Resources

About