Alpelisib: First Global Approval

Markham, Anthony

doi:10.1007/s40265-019-01161-6

Cited by 193 publications

(117 citation statements)

References 8 publications

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“…PIK3CA is one of the most mutated oncogenes in human malignancies and there are numerous PI3K inhibitors undergoing clinical trials. This recently resulted in the approval of Alpelisib/BYL719 for advanced PIK3CA mutation positive, hormone receptor positive, HER2 negative breast cancer patients 7 . Therefore, to identify these Here we describe a simple and robust workflow to enrich and detect common oncogenic PIK3CA E542K, E545K, H1047R and H1047L mutations in human genomic DNA.…”

Section: Discussionmentioning

confidence: 99%

“…Substantial investment and research has succeeded in producing a range of small molecule drugs targeting PI3K, which have undergone clinical trials in cancer patients. Such trials have recently resulted in the FDA approval of Alpelisib/BYL719, a PI3K p110α selective inhibitor for advanced breast cancers which are hormone receptor positive, HER2 negative and PIK3CA mutant 7 . This and other clinical circumstances [8][9][10][11][12][13][14][15] identify PIK3CA status as an important biomarker with both predictive and prognostic value, and motivate the development of reliable, facile, economic tests for these mutations.…”

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confidence: 99%

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PIK3CA mutation enrichment and quantitation from blood and tissue

Keraite

Álvarez‐García

García-Murillas

et al. 2020

Sci Rep

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PIK3CA is one of the two most frequently mutated genes in breast cancers, occurring in 30–40% of cases. Four frequent ‘hotspot’ PIK3CA mutations (E542K, E545K, H1047R and H1047L) account for 80–90% of all PIK3CA mutations in human malignancies and represent predictive biomarkers. Here we describe a PIK3CA mutation specific nuclease-based enrichment assay, which combined with a low-cost real-time qPCR detection method, enhances assay detection sensitivity from 5% for E542K and 10% for E545K to 0.6%, and from 5% for H1047R to 0.3%. Moreover, we present a novel flexible prediction method to calculate initial mutant allele frequency in tissue biopsy and blood samples with low mutant fraction. These advancements demonstrated a quick, accurate and simple detection and quantitation of PIK3CA mutations in two breast cancer cohorts (first cohort n = 22, second cohort n = 25). Hence this simple, versatile and informative workflow could be applicable for routine diagnostic testing where quantitative results are essential, e.g. disease monitoring subject to validation in a substantial future study.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

PIK3CA mutation enrichment and quantitation from blood and tissue

Keraite

Álvarez‐García

García-Murillas

et al. 2020

Sci Rep

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“…CDK4 and CDK6 kinase inhibitors have been approved as a therapy for patients with estrogen receptor-positive and HER2-negative tumors (8). Patients with the same type of tumors, bearing mutations in the PIK3CA gene have been approved for PI3K kinase inhibitors (9). In the case of TNBCs, a high percentage have been shown to exhibit expression of PD-L1, a PD-1 ligand that inactivates the immune response.…”

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confidence: 99%

An Overview of Vasculogenic Mimicry in Breast Cancer

et al. 2020

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Vasculogenic mimicry (VM) is the formation of vascular channels lacking endothelial cells. These channels are lined by tumor cells with cancer stem cell features, positive for periodic acid-Schiff, and negative for CD31 staining. The term VM was introduced by Maniotis et al. (1), who reported this phenomenon in highly aggressive uveal melanomas; since then, VM has been associated with poor prognosis, tumor aggressiveness, metastasis, and drug resistance in several tumors, including breast cancer. It is proposed that VM and angiogenesis (the de novo formation of blood vessels from the established vasculature by endothelial cells, which is observed in several tumors) rely on some common mechanisms. Furthermore, it is also suggested that VM could constitute a means to circumvent anti-angiogenic treatment in cancer. Therefore, it is important to determinant the factors that dictate the onset of VM. In this review, we describe the current understanding of VM formation in breast cancer, including specific signaling pathways, and cancer stem cells. In addition, we discuss the clinical significance of VM in prognosis and new opportunities of VM as a target for breast cancer therapy.

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“…This in contrast to amplification of PI3K/AKT that has been associated with radioresistance 27 . Alpelisib, the first PI3K inhibitor approved by the FDA, is approved to treat breast cancer patients with PIK3CA-mutation 28 . The selectivity of Alpelisib for PIK3CA-mutated cells has also been seen in HNSCC cells by Keam et al 29 .…”

Section: Discussionmentioning

confidence: 99%

The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells

Glorieux

Dok

Nuyts

2020

Sci Rep

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Radiotherapy has a central role in the treatment of head and neck squamous cell carcinoma (HNSCC). Activation of the PI3K/AKT/mTOR pathway can decrease the efficiency of radiotherapy via the promotion of cell survival and DNA repair. Here, the influence of PI3K pathway inhibition on radiotherapy response was investigated. Two PI3K inhibitors were investigated and both BKM120 and GDC0980 effectively inhibited cellular and clonogenic growth in 6 HNSCC cells, both HPV-positive as well as HPV-negative. Despite targeted inhibition of the pathway and slight increase in DNA damage, PI3K inhibition did not show significant radiosensitization. Currently only one clinical trial is assessing the effectiveness of combining BKM120 with RT in HNSCC (NCT02113878) of which the results are eagerly awaited.

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Alpelisib: First Global Approval

Cited by 193 publications

References 8 publications

PIK3CA mutation enrichment and quantitation from blood and tissue

PIK3CA mutation enrichment and quantitation from blood and tissue

An Overview of Vasculogenic Mimicry in Breast Cancer

The influence of PI3K inhibition on the radiotherapy response of head and neck cancer cells

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