PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer

Gschwantler‐Kaulich, Daphne; Tan, Yen Y.; Fuchs, Eva-Maria; Hudelist, Gernot; Köstler, Wolfgang J.; Angelika, Reiner; Leser, Carmen; Salama, Mohamed; Attems, Johannes; Deutschmann, Christine; Zielinski, Christoph; Singer, Christian F.

doi:10.1371/journal.pone.0172911

Cited by 12 publications

(4 citation statements)

References 39 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, a reduced or absent of PTEN expression in breast cancer tissue was only in 28 out 85 of breast cancer patients (33%) in the Engin et al, (2006) study, which was using IHC for the detection of PTEN. There were other studies did not correspond to our data in this study, and reported decreased or absent PTEN expression in breast carcinoma tissue in high percentage among the breast cancer patients (Kechagioglou et al, 2014;Gschwantler-Kaulich et al, 2017;Shabbir et al, 2017). As listed in Table 2, PTEN expression did not have any relation to any clinicopathological factors (P>0.05), there were also some studies that showed no association between PTEN expression and clinicopathological factors of breast cancer.…”

Section: Discussioncontrasting

confidence: 62%

PIK3CA and PTEN Genes Expressions in Breast Cancer

Alowiri

Hanafy

Haleem

et al. 2019

Asian Pac J Cancer Prev

View full text Add to dashboard Cite

The molecular biomarkers, and their correlation with pathological parameters are very important for diagnosis, prognosis, predictive utility, management, and prevention of breast cancer (Patani et al., 2013). The phosphatidylinositol-3-kinase (PI3K) pathway is an important signaling pathway in cells and is involved in essential cellular functions such as metabolism, proliferation, survival, motility, and growth and plays a main role in development and progression of breast cancer (Engelman et al., 2006; Boyault et al., 2012). Based on structure, regulation, and substrate specificity, the PI3K family is classified into three classes, class I, class II, and class III (Leevers et al., 1999). Class I is divided to IA and IB, class IA PI3K is composed of two subunits: A regulatory subunit (85 kDa), and a catalytic

show abstract

Section: Discussioncontrasting

confidence: 62%

PIK3CA and PTEN Genes Expressions in Breast Cancer

Alowiri

Hanafy

Haleem

et al. 2019

Asian Pac J Cancer Prev

View full text Add to dashboard Cite

show abstract

“…In addition to its role in the suppression of cell proliferation and migration, PTEN is well known for its function in modulating cancer cell responses to drug treatment (24,25). In NSCLC, promoter methylation was initially reported to account for PTEN silencing, with ~35% of PTEN-negative NSCLC patients exhibiting high levels of promoter methylation (26).…”

Section: Discussionmentioning

confidence: 99%

miRNA‑328 overexpression confers cisplatin resistance in non‑small cell lung cancer via targeting of PTEN

Wang

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

Chemotherapy resistance, the molecular mechanism of which is complex and has not been fully understood, poses a major challenge in the treatment of patients with non‑small cell lung cancer (NSCLC). The dysregulation of microRNAs (miRs) has been reported to serve a pivotal role in the development of cancer and drug resistance. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant increase in miR‑328 and a significant decrease in phosphatase and tensin homolog (PTEN) mRNA expression levels within tumor tissues from patients with cisplatin‑resistant NSCLC compared with those of cisplatin‑sensitive NSCLC patients. In addition, there was a negative correlation between PTEN mRNA and the miR‑328 expression levels. In addition, higher miR‑328 expression levels, and lower PTEN mRNA and protein expression levels, were detected in cisplatin‑resistant A549 (A549rCDDP) cells when compared with in their parental cells. A549rCDDP cells demonstrated significantly higher cell viability compared with A549 cells following treatment with all concentrations of cisplatin tested (2, 4, 6 and 8 µM). Additionally, transfection of miR‑328 inhibitor significantly increased PTEN mRNA and protein expression levels. Furthermore, the present study predicted and confirmed PTEN, a well‑known tumor suppressor, as a direct target of miR‑328 in NSCLC cells via the online tool MiRanda and a dual luciferase assay, respectively. Cell viability assay and flow cytometry analysis demonstrated that inhibition of miR‑328 also induced cellular apoptosis and decreased cell proliferation in A549rCDDP cells treated with cisplatin. In conclusion, these results suggested that abnormal expression of miR‑328 may contribute to cisplatin resistance in NSCLC, and may be considered to be a novel therapeutic target and indicator for the treatment and prognosis of patients with NSCLC treated with cisplatin‑based chemotherapy.

show abstract

“…However, since the number of HER2+ patients in this study was very small ( n = 23), the results should be interpreted with care. Moreover, there are reports on the relationship between PTEN expression and response to the trastuzumab-containing therapy in HER2+ breast cancer [ 21 ]. In summary, comprehensive studies on the potential biomarkers of HER2+ GC, whether they be clinical or molecular, are still lacking and need to be pursued.…”

Section: Discussionmentioning

confidence: 99%

PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer

et al. 2017

View full text Add to dashboard Cite

BackgroundTrastuzumab is an active agent against human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC). This study aimed to characterize resistance to trastuzumab-based front-line chemotherapy in HER2+ GC patients and to establish factors predictive of this resistance.ResultsAmong 129 HER2+ GC patients, 25% displayed rapid disease progression within 4 months from initiation of therapy. These patients showed a higher rate of signet ring cell histology, bone metastasis, poor performance status, frequent loss of PTEN expression, and low HER2 amplification index compared with patients who were progression-free for at least 4 months. In contrast, there was no significant difference in the frequency of the PIK3R1 variant. Multivariate analyses confirmed two independent molecular predictors for trastuzumab resistance: loss of PTEN expression and low HER2 amplification index (<5). Patients with one or both molecular predictors at diagnosis exhibited worse progression-free and overall survival compared to those without risk factors (p < 0.001 and p = 0.001, respectively).ConclusionIn HER2+ GC patients, loss of PTEN expression and low HER2 AI correlated with resistance to trastuzumab-based therapy and dismal prognosis. Since patients harboring these molecular predictors are unlikely to respond to trastuzumab-based therapy, other novel therapeutic targets needed to be considered.MethodsHER2+ GC patients who were treated with trastuzumab in combination with either 5-fluorouracil/cisplatin or capecitabine/cisplatin were enrolled. Clinicopathologic features and molecular alterations of HER2, phosphoinositide 3-kinase regulatory subunit 1 (PIK3R1), and phosphatase and tensin homolog (PTEN) were correlated with treatment outcome. Factors predictive of resistance were also explored.

show abstract

PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer

Cited by 12 publications

References 39 publications

PIK3CA and PTEN Genes Expressions in Breast Cancer

PIK3CA and PTEN Genes Expressions in Breast Cancer

miRNA‑328 overexpression confers cisplatin resistance in non‑small cell lung cancer via targeting of PTEN

PTEN loss and level of HER2 amplification is associated with trastuzumab resistance and prognosis in HER2-positive gastric cancer

Contact Info

Product

Resources

About