A review of the use of next generation sequencing methodologies to identify biomarkers of resistance to CDK4/6 inhibitors in ER+/HER2- breast cancer

Servetto, Alberto; Napolitano, Fabiana; Angelis, Carmine De; Placido, Pietro De; Giuliano, Mario; Arpino, Grazia; Placido, Sabino De; Bianco, Roberto; Formisano, Luigi

doi:10.1016/j.critrevonc.2020.103191

Cited by 11 publications

(9 citation statements)

References 104 publications

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“…Our results indicated that oral cancer patients with high expression levels of GBP5 have poor DFS, which is usually caused by chemotherapy resistance-associated cancer stemness [24]. Here, we found that GBP5 knockdown decreased several chemotherapy resistance-associated cancer stemness markers such as ALDH1A1 [40], ALDH1A2 [41], CD44 [42], CD166 [9], and ABCG2 [43]. In the study, we found that the tumorsphere formation, chemoresistance, and expressions of stemness-related surface markers were all decreased in GBP5-silenced cells, implying that GBP5 expression may directly or indirectly influence the expression levels of genes involved in stem cell physiology.…”

Section: Discussionmentioning

confidence: 52%

“…High-throughput profiling techniques such as RNA-sequencing (RNA-seq) using next-generation sequencing (NGS) [9] and RNAi high-throughput screening (HTS) [10] have been used to identify gene expression associated with many diseases such as cancer, and could provide a very powerful tool for discovering cancer biomarkers and therapeutic targets, especially for OSCC. For example, we have identified GBP6 as a favorable cancer biomarker in TSCC by NGS [11].…”

Section: Introductionmentioning

confidence: 99%

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Clinical Significance and the Role of Guanylate-Binding Protein 5 in Oral Squamous Cell Carcinoma

Liu

Shu

Lee

et al. 2021

Cancers

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Guanylate binding protein 5 (GBP5) is the interferon (IFN)-inducible subfamily of guanosine triphosphatases (GTPases) and is involved in pathogen defense. However, the role played by GBP5 in cancer development, especially in oral squamous cell carcinoma (OSCC), is still unknown. Herein, next-generation sequencing analysis showed that the gene expression levels of GBP5 were significantly higher in OSCC tissues compared with those found in corresponding tumor adjacent normal tissues (CTAN) from two pairs of OSCC patients. Higher gene expression levels of GBP5 were also found in tumor tissues of 23 buccal mucosal squamous cell carcinoma (BMSCC)/14 tongue squamous cell carcinoma (TSCC) patients and 30 oral cancer patients from The Cancer Genome Atlas (TCGA) database compared with those in CTAN tissues. Immunohistochemical results showed that protein expression levels of GBP5 were also higher in the tumor tissues of 353 OSCC patients including 117 BMSCC, 187 TSCC, and 49 lip squamous cell carcinoma patients. Moreover, TCGA database analysis indicated that high gene expression levels of GBP5 were associated with poor overall survival in oral cancer patients with moderate/poor cell differentiation, and associated with poor disease-free survival in oral cancer patients with moderate/poor cell differentiation and lymph node metastasis. Furthermore, GBP5-knockdowned cells exhibited decreased cell growth, arrest at G1 phase, and decreased invasion/migration. The gene expression of markers for epithelial−mesenchymal transition and cancer stemness was also reduced in GBP5-silenced oral cancer cells. Taken together, GBP5 might be a potential biomarker and therapeutic target for OSCC patients, especially for those with poor cell differentiation and lymph node metastasis.

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Section: Discussionmentioning

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Clinical Significance and the Role of Guanylate-Binding Protein 5 in Oral Squamous Cell Carcinoma

Liu

Shu

Lee

et al. 2021

Cancers

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“…Understanding the mechanism of the resistance to CDK4/6i is critical for personalized treatment in breast cancer. Multiple studies were conducted to understand the molecular mechanisms of resistance to CDK 4/6i in breast cancer [33,34]. Paired baseline and end-of-treatment ctDNA from 195 patients in the PALOMA-3 was studied [16] and showed that acquired mutations (mut) in RB1 occurred in 5% of patients after palbociclib.…”

Section: Discussionmentioning

confidence: 99%

Genomic Markers of CDK 4/6 Inhibitor Resistance in Hormone Receptor Positive Metastatic Breast Cancer

Lee

Yost

et al. 2022

Cancers

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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 clinical practice. Patients with HR+ MBC treated with palbociclib, ribociclib, or abemaciclib and antiestrogen therapy were identified. Patients were grouped into early (<6 months); intermediate (6–24 months for 0–1 lines; 6–9 months for ≥2 lines); or late progressors (>24 months for 0–1 lines; >9 months PFS for ≥2 lines). NGS and RNA sequencing data were analyzed in association with PFS, and survival analysis was stratified by prior lines of chemotherapy. A total of 795 patients with HR+ MBC treated with CDK 4/6i were identified. Of these, 144 (18%) patients had genomic data and 29 (3.6%) had RNA data. Among the 109 patients who received CDK4/6i as 1st- or 2nd-line therapy, 17 genes showed associations with PFS (p-value ≤ 0.15 and HR ≥ 1.5 or HR < 0.5). Whole transcriptome RNAseq was analyzed for 24/109 (22%) patients with 0–1 prior lines of therapy and 56 genes associated with PFS (HR ≥ 4 or HR ≤ 0.25 and FDR ≤ 0.15). In this retrospective analysis, genomic biomarkers including FGFR1 amplification, PTEN loss, and DNA repair pathway gene mutations showed significant associations with shorter PFS for patients receiving CDK4/6 inhibitor therapy.

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“…12 CDK4/6 enzymes regulate the activity of the tumor suppressor protein retinoblastoma (Rb). 14,15 When activated, CDK4/6 kinases lead to Rb hyperphosphorylation and progression through the cell cycle resulting in cell proliferation. CDK4/6 inhibitors block Rb hyperphosphorylation resulting in G1 cell arrest.…”

Section: Pharmacologymentioning

confidence: 99%

Abemaciclib: The First FDA-Approved CDK4/6 Inhibitor for the Adjuvant Treatment of HR+ HER2− Early Breast Cancer

et al. 2022

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Objective: To review the new indication of cyclin-dependent kinase (CDK4/6) inhibitor abemaciclib for the adjuvant treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−), axillary lymph node (LN) positive early breast cancer (EBC) at high risk of recurrence and a Ki-67 ≥20%. Data Sources: A literature search was performed through PubMed, ClinicalTrials.gov, and Food and Drug Administration (FDA) website (February 1, 2018, to December 23, 2021) to identify relevant information. Study Selection and Data Extraction: Human and animal studies related to pharmacology, pharmacokinetics, efficacy, and safety of abemaciclib were identified. Data Synthesis: Addition of abemaciclib to standard of care endocrine therapy (ET) for patients with high-risk clinicopathologic features and Ki-67 ≥20% demonstrated 30% reduction in the risk of developing invasive disease and distant recurrence. At 15.5 months, abemaciclib + ET demonstrated a significant improvement in invasive disease-free survival (IDFS) vs ET alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.93, P = 0.01). At 27 months, IDFS benefit was maintained (HR, 0.70; 95% CI, 0.59-0.82, P < 0.0001). Diarrhea occurred in more than 80% of patients in the abemaciclib arm. Relevance to Patient Care and Clinical Practice: This review describes the clinical applicability of adjuvant abemaciclib for patients with HR+, HER2− EBC at high risk for recurrence. Conclusion: Adjuvant abemaciclib significantly reduces the risk for early development of invasive disease and distant recurrence in patients with HR+, HER2− node positive EBC. Longer follow-up is needed to determine the impact of adjuvant abemaciclib on late disease recurrence and survival outcomes.

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A review of the use of next generation sequencing methodologies to identify biomarkers of resistance to CDK4/6 inhibitors in ER+/HER2- breast cancer

Cited by 11 publications

References 104 publications

Clinical Significance and the Role of Guanylate-Binding Protein 5 in Oral Squamous Cell Carcinoma

Clinical Significance and the Role of Guanylate-Binding Protein 5 in Oral Squamous Cell Carcinoma

Genomic Markers of CDK 4/6 Inhibitor Resistance in Hormone Receptor Positive Metastatic Breast Cancer

Abemaciclib: The First FDA-Approved CDK4/6 Inhibitor for the Adjuvant Treatment of HR+ HER2− Early Breast Cancer

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