A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

Han, Yu; Lee, Jae Ho; Park, Ga-Young; Chun, Sung Hak; Han, Jeong Yun; Kim, Sung Dae; Lee, Janet; Lee, Chang-Woo; Yang, Kwangmo; Lee, Chang Geun

doi:10.1016/j.bbrc.2012.10.119

Cited by 22 publications

(17 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study also suggested that silencing CDK4/6 increases radiation-induced cell death but does not significantly alter cell cycle progression or interfere with DNA repair following radiation exposure [87]. The mechanism of CDK4/6 inhibitor radiosensitization may be related to the induction of cancer stem cell differentiation, which increases the vulnerability of cells to radiation-induced cell death [88]. The possible clinical benefits of CDK4/6 blockade on radiation sensitization need to be further explored.…”

Section: Radiotherapymentioning

confidence: 83%

Targeting CDK4/6 in patients with cancer

Hamilton

Infante

2016

Cancer Treatment Reviews

373

298

View full text Add to dashboard Cite

The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway controls cell cycle progression by regulating the G1-S checkpoint. Dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway results in increased proliferation, and is frequently observed in many types of cancer. Pathway activation can occur through a variety of mechanisms, including gene amplification or rearrangement, loss of negative regulators, epigenetic alterations, and point mutations in key pathway components. Due to the importance of CDK4/6 activity in cancer cells, CDK4/6 inhibitors have emerged as promising candidates for cancer treatment. Moreover, combination of a CDK4/6 inhibitor with other targeted therapies may help overcome acquired or de novo treatment resistance. Ongoing studies include combinations of CDK4/6 inhibitors with endocrine therapy and phosphatidylinositol 3-kinase (PI3K) pathway inhibitors for hormone receptor-positive (HR+) breast cancers, and with selective RAF and MEK inhibitors for tumors with alterations in the mitogen activated protein kinase (MAPK) pathway such as melanoma. In particular, the combination of CDK4/6 inhibitors with endocrine therapy, such as palbociclib's recent first-line approval in combination with letrozole, is expected to transform the treatment of HR+ breast cancer. Currently, three selective CDK4/6 inhibitors have been approved or are in late-stage development: palbociclib (PD-0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Here we describe the current preclinical and clinical data for these novel agents and discuss combination strategies with other agents for the treatment of cancer.

show abstract

Section: Radiotherapymentioning

confidence: 83%

Targeting CDK4/6 in patients with cancer

Hamilton

Infante

2016

Cancer Treatment Reviews

373

298

View full text Add to dashboard Cite

show abstract

“…Constitutive expression of CDK4 results in hyperphosphorylation of Rb and increased E2F activity, leading to inappropriate progression through the G1/S phase of the cell cycle [40]. In previous study, the genes (CDK1, CDK2 and CDK4) were dysregulated in breast cancer [42], ovarian cancer [43], colon cancer [44], hepatocellular carcinoma [45], thyroid carcinoma [46], and lung cancer [47]. We also found that the high expression of CDK1, CDK2 and CDK4, part of cyclin-dependent kinases, were related to tumorigenesis in LSCC, and the results were validated by qRT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Microarray Gene Expression Analysis of Tumorigenesis and Regional Lymph Node Metastasis in Laryngeal Squamous Cell Carcinoma

et al. 2013

View full text Add to dashboard Cite

BackgroundLaryngeal squamous cell carcinoma (LSCC) is the most common type in head and neck squamous cell carcinoma (HNSCC), and the development and progression of LSCC are multistep processes accompanied by changes of molecular biology.ObjectiveThe purpose of this study was to investigate the molecular basis of tumorigenesis and regional lymph node metastasis in LSCC, and provide a set of genes that may be useful for the development of novel diagnostic markers and/or more effective therapeutic strategies.MethodsA total number of 10 patients who underwent surgery for primary laryngeal squamous cell carcinoma were recruited for microarray analysis. LSCC tissues compared with corresponding adjacent non-neoplastic tissues were analysed by Illumina mRNA microarrays, and LSCC tissues with regional lymph node metastasis and LSCC tissues without regional lymph node metastasis were analyzed in the same manner. The most frequently differently expressed genes screened by microarrays were also validated by qRT-PCR in another 42 patients diagnosed for LSCC.ResultsAnalysed by Illumina mRNA microarrays, there were 361 genes significantly related to tumorigenesis while 246 genes significantly related to regional lymph node metastasis in LSCC. We found that the six genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4) were most frequently differently expressed functional genes related to tumorigenesis while eIF3a and RPN2 were most frequently differently expressed functional genes related to regional lymph node metastasis in LSCC. The expressions of these genes were also validated by qRT-PCR.ConclusionsThe research revealed a gene expression signature of tumorigenesis and regional lymph node metastasis in laryngeal squamous cell carcinoma. Of the total, the deregulation of several genes (CDK1, CDK2, CDK4, MCM2, MCM3, MCM4, EIF3a and RPN2) were potentially associated with disease development and progression. The result will contribute to the understanding of the molecular basis of LSCC and help to improve diagnosis and treatment.

show abstract

“…Half-million MCF-7 or MDA-MB-231 breast cancer cells, known to contain functional cancer stem cells [6,[33][34][35], were incubated with F3 peptide-or non-targeted rhodamine-labelled liposomes, or liposomes targeted by a non-specific peptide, at 0.4 mM of total lipid, for 1 h at 37ºC or 4ºC. After washing, cells were stained aiming at identifying cancer stem cells, as previously described [33].…”

Section: Cellular Association Of F3 Peptide-targeted Nanoparticles Wimentioning

confidence: 99%

“…Afterwards, sorting of ALDH hi /CD44 hi and ALDH low/-/CD44 low/-cells was performed with a BD FACSAria III cell sorter (BD Biosciences, USA), collecting 5-15% and 15-20% of each selected sub-population, respectively, depending on the cell line tested [33]. Sorted cells were then seeded for mammosphere formation, as previously described [34,36]. Briefly, 5000 single ALDH hi /CD44 hi or ALDH low/-/CD44 low/-cells were seeded in 2 mL Mammocult® Medium supplemented with 4 µg/mL of RNA were stored at -80°C until use [38].…”

Section: Establishment Of Mammospheres From Sorted Sub-populationsmentioning

confidence: 99%

Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination

et al. 2015

View full text Add to dashboard Cite

A possible usage of a CDK4 inhibitor for breast cancer stem cell-targeted therapy

Cited by 22 publications

References 31 publications

Targeting CDK4/6 in patients with cancer

Targeting CDK4/6 in patients with cancer

Microarray Gene Expression Analysis of Tumorigenesis and Regional Lymph Node Metastasis in Laryngeal Squamous Cell Carcinoma

Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination

Contact Info

Product

Resources

About