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Article ; Online: Lasofoxifene Monotherapy Induces Durable Complete Remission in a Patient with Estrogen Receptor-Positive, Metastatic Breast Cancer with an

Gal-Yam, Einav Nili / Levanon, Keren

JCO precision oncology

2023 Volume 7, Page(s) e2300097

MeSH term(s)	Humans ; Female ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Pyrrolidines ; Receptors, Estrogen/genetics ; Mutation
Chemical Substances	Lasofoxifene (337G83N988) ; Pyrrolidines ; Receptors, Estrogen
Language	English
Publishing date	2023-12-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.23.00097
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Article ; Online: Candidate RNA biomarkers in biofluids for early diagnosis of ovarian cancer: A systematic review.

Hulstaert, Eva / Morlion, Annelien / Levanon, Keren / Vandesompele, Jo / Mestdagh, Pieter

Gynecologic oncology

2020 Volume 160, Issue 2, Page(s) 633–642

Abstract: Ovarian cancer is often diagnosed in an advanced stage and is associated with a high mortality rate. It is assumed that early detection of ovarian cancer could improve patient outcomes. Unfortunately, effective screening methods for early diagnosis of ... ...

Abstract	Ovarian cancer is often diagnosed in an advanced stage and is associated with a high mortality rate. It is assumed that early detection of ovarian cancer could improve patient outcomes. Unfortunately, effective screening methods for early diagnosis of ovarian cancer are still lacking. Extracellular RNAs circulating in human biofluids can reliably be measured and are emerging as potential biomarkers in cancer. In this systematic review, we present 75 RNA biomarkers detectable in human biofluids that have been studied for early diagnosis of ovarian cancer. The majority of these markers are microRNAs identified using RT-qPCR or microarrays in blood-based fluids. A handful of studies used RNA-sequencing and explored alternative fluids, such as urine and ascites. Candidate RNA biomarkers that were more abundant in biofluids of ovarian cancer patients compared to controls in at least two independent studies include miR-21, the miR-200 family, miR-205, miR-10a and miR-346. Amongst the markers confirmed to be lower in at least two studies are miR-122, miR-193a, miR-223, miR-126 and miR-106b. While these biomarkers show promising diagnostic potential, further validation is required before implementation in routine clinical care. Challenges related to biomarker validation and reflections on future perspectives to accelerate progress in this field are discussed.
MeSH term(s)	Ascitic Fluid/chemistry ; Ascitic Fluid/pathology ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Carcinoma, Ovarian Epithelial/blood ; Carcinoma, Ovarian Epithelial/diagnosis ; Carcinoma, Ovarian Epithelial/genetics ; Carcinoma, Ovarian Epithelial/urine ; Early Detection of Cancer/methods ; Female ; Humans ; Liquid Biopsy/methods ; MicroRNAs/analysis ; MicroRNAs/genetics ; Ovarian Neoplasms/blood ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/urine ; RNA-Seq
Chemical Substances	Biomarkers, Tumor ; MicroRNAs
Language	English
Publishing date	2020-11-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2020.11.018
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Zs.A 885: Show issues

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Article ; Online: RNA biomarkers from proximal liquid biopsy for diagnosis of ovarian cancer.

Hulstaert, Eva / Levanon, Keren / Morlion, Annelien / Van Aelst, Stefan / Christidis, Anthony-Alexander / Zamar, Ruben / Anckaert, Jasper / Verniers, Kimberly / Bahar-Shany, Keren / Sapoznik, Stav / Vandesompele, Jo / Mestdagh, Pieter

Neoplasia (New York, N.Y.)

2022 Volume 24, Issue 2, Page(s) 155–164

Abstract: Background: Most ovarian cancer patients are diagnosed at an advanced stage and have a high mortality rate. Current screening strategies fail to improve prognosis because markers that are sensitive for early stage disease are lacking. This medical need ... ...

Abstract	Background: Most ovarian cancer patients are diagnosed at an advanced stage and have a high mortality rate. Current screening strategies fail to improve prognosis because markers that are sensitive for early stage disease are lacking. This medical need justifies the search for novel approaches using utero-tubal lavage as a proximal liquid biopsy. Methods: In this study, we explore the extracellular transcriptome of utero-tubal lavage fluid obtained from 26 ovarian cancer patients and 48 controls using messenger RNA (mRNA) capture and small RNA sequencing. Results: We observed an enrichment of ovarian and fallopian tube specific messenger RNAs in utero-tubal lavage fluid compared to other human biofluids. Over 300 mRNAs and 41 miRNAs were upregulated in ovarian cancer samples compared with controls. Upregulated genes were enriched for genes involved in cell cycle activation and proliferation, hinting at a tumor-derived signal. Conclusion: This is a proof-of-principle that mRNA capture sequencing of utero-tubal lavage fluid is technically feasible, and that the extracellular transcriptome of utero-tubal lavage should be further explored in larger cohorts to assess the diagnostic value of the biomarkers identified in this study. Impact: Proximal liquid biopsy from the gynecologic tract is a promising source for mRNA and miRNA biomarkers for diagnosis of early-stage ovarian cancer.
MeSH term(s)	Biomarkers, Tumor ; Case-Control Studies ; Cell-Free Nucleic Acids ; Early Detection of Cancer ; Female ; Humans ; Liquid Biopsy/methods ; MicroRNAs/genetics ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/genetics ; Prognosis ; RNA ; RNA, Messenger/genetics
Chemical Substances	Biomarkers, Tumor ; Cell-Free Nucleic Acids ; MicroRNAs ; RNA, Messenger ; RNA (63231-63-0)
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1483840-0
ISSN	1476-5586 ; 1522-8002
ISSN (online)	1476-5586
ISSN	1522-8002
DOI	10.1016/j.neo.2021.12.008
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Zs.A 5203: Show issues

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Article ; Online: The Role of 68 Ga-FAPI PET/CT in Detection of Metastatic Lobular Breast Cancer.

Eshet, Yael / Tau, Noam / Apter, Sara / Nissan, Noam / Levanon, Keren / Bernstein-Molho, Rinat / Globus, Ofer / Itay, Amit / Shapira, Tal / Oedegaard, Cecilie / Gorfine, Malka / Eifer, Michal / Davidson, Tima / Gal-Yam, Einav / Domachevsky, Liran

Clinical nuclear medicine

2023 Volume 48, Issue 3, Page(s) 228–232

Abstract: Purpose: Invasive lobular breast cancer (ILC) may be hard to detect using conventional imaging modalities and usually shows less avidity to 18 F-FDG PET/CT. 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT has shown promising results in ... ...

Abstract	Purpose: Invasive lobular breast cancer (ILC) may be hard to detect using conventional imaging modalities and usually shows less avidity to 18 F-FDG PET/CT. 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT has shown promising results in detecting non- 18 F-FDG-avid cancers. We aimed to assess the feasibility of detecting metastatic disease in patients with non- 18 F-FDG-avid ILC. Methods: This prospective study included patients with metastatic ILC, infiltrative to soft tissues, which was not 18 F-FDG avid. The patients underwent 68 Ga-FAPI PET/CT for evaluation, which was correlated with the fully diagnostic CT performed at the same time. Results: Seven women (aged 57 ± 10 years) were included. Among the 30 organs and structures found to be involved by tumor, the number of findings observed by FAPI PET/CT was significantly higher than that observed by CT alone ( P = 0.022), especially in infiltrative soft tissue and serosal locations. Conclusions: This small pilot trial suggests a role for 68 Ga-FAPI PET/CT in ILC, which needs to be confirmed by subsequent trials.
MeSH term(s)	Humans ; Female ; Positron Emission Tomography Computed Tomography ; Breast Neoplasms/diagnostic imaging ; Fluorodeoxyglucose F18 ; Prospective Studies ; Carcinoma, Lobular/diagnostic imaging ; Gallium Radioisotopes
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Gallium-68 (98B30EPP5S) ; abamectin (5U8924T11H) ; Gallium Radioisotopes
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	197628-x
ISSN	1536-0229 ; 0363-9762
ISSN (online)	1536-0229
ISSN	0363-9762
DOI	10.1097/RLU.0000000000004540
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Zs.A 1276: Show issues

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Article ; Online: The Role of 68 Ga-FAPI PET/CT in Breast Cancer Response Assessment and Follow-Up.

Eshet, Yael / Tau, Noam / Levanon, Keren / Bernstein-Molho, Rinat / Globus, Ofer / Itay, Amit / Shapira, Tal / Oedegaard, Cecilie / Eifer, Michal / Davidson, Tima / Nidam, Meital / Gal-Yam, Einav / Domachevsky, Liran

Clinical nuclear medicine

2023 Volume 48, Issue 8, Page(s) 685–688

Abstract: Purpose: 68 Ga-fibroblast activation protein inhibitor (FAPI), a new PET/CT radiotracer targeting cancer-associated fibroblasts in tumor microenvironment, can detect many types of cancer. We aimed to assess whether it can also be used for response ... ...

Abstract	Purpose: 68 Ga-fibroblast activation protein inhibitor (FAPI), a new PET/CT radiotracer targeting cancer-associated fibroblasts in tumor microenvironment, can detect many types of cancer. We aimed to assess whether it can also be used for response assessment and follow-up. Methods: We followed up patients with FAPI-avid invasive lobular breast cancer (ILC) before and after treatment changes and correlated qualitative maximal intensity projection images and quantitative tumor volume with CT results and blood tumor biomarkers. Results: Six consenting ILC breast cancer patients (53 ± 8 years old) underwent a total of 24 scans (baseline for each patient and 2-4 follow-up scans). We found a strong correlation between 68 Ga-FAPI tumor volume and blood biomarkers ( r = 0.7, P < 0.01), but weak correlation between CT and 68 Ga-FAPI maximal intensity projection-based qualitative response assessment. Conclusions: We found a strong correlation between ILC progression and regression (as assessed by blood biomarkers) and 68 Ga-FAPI tumor volume. 68 Ga-FAPI PET/CT could possibly be used for disease response assessment and follow-up.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/diagnostic imaging ; Positron Emission Tomography Computed Tomography ; Follow-Up Studies ; Biomarkers, Tumor/blood ; Middle Aged ; Prospective Studies
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2023-06-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	197628-x
ISSN	1536-0229 ; 0363-9762
ISSN (online)	1536-0229
ISSN	0363-9762
DOI	10.1097/RLU.0000000000004744
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Zs.A 1276: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Immunotherapy in mismatch repair-deficient metastatic colorectal cancer - Outcome and novel predictive markers.

Stemmer, Amos / Margalit, Ofer / Serpas, Victoria / Strauss, Gal / Thomas, Jane / Shah, Preksha / Tau, Noam / Levanon, Keren / Shacham-Shmueli, Einat / Kopetz, Scott / Overman, Michael / Boursi, Ben

European journal of cancer (Oxford, England : 1990)

2023 Volume 198, Page(s) 113495

Abstract: Background: This study aims to assess predictive markers for response to immunotherapy in dMMR/MSI-H metastatic colorectal cancer (mCRC) patients.: Materials and methods: A study using two prospective cohorts from MD Anderson Cancer Center and Sheba ... ...

Abstract	Background: This study aims to assess predictive markers for response to immunotherapy in dMMR/MSI-H metastatic colorectal cancer (mCRC) patients. Materials and methods: A study using two prospective cohorts from MD Anderson Cancer Center and Sheba Medical Center of consecutive patients with dMMR/MSI-H mCRC that were treated with immunotherapy between 2014-2022. Primary outcome was progression-free survival (PFS) and secondary outcome was overall response rate (ORR). Evaluated predictors included ECOG-PS score, RAS/BRAF status, single-agent versus doublet immunotherapy, metastatic sites, disease burden, and CEA levels prior to treatment initiation. Kaplan-Meier analysis and Cox proportional hazard regression model were used to analyze the effect of exposure variables on PFS. Results: The study included 153 patients. Median follow-up time was 26 months (IQR 11-48). Median PFS was 51.6 months (95%CI 38.1-NR) and ORR was 58.1%. In a univariate analysis, male sex was associated with worse PFS with a HR of 1.67 (95% CI 1.00-2.79); Right-sided tumors were associated with improved PFS with a HR of 0.56 (95% CI 0.32-0.97); Liver or lung metastasis were associated with worse PFS with HRs of 2.35 (95%CI 1.43-3.88) and 2.30 (95%CI 1.31-4.04), respectively; ECOG-PS score ≥ 2, CEA levels ˃5 μg/L prior to treatment initiation and ≥ 3 metastatic sites were associated with worse PFS with HRs of 2.09 (95%CI 0.98-4.47), 2.23 (95%CI 1.30-3.81) and 3.11 (95%CI 1.61-6.03), respectively. Liver or lung metastasis remained significant in a multivariable model. Conclusions: Extent of disease (worse PFS with high CEA, poor ECOG-PS and ≥3 metastatic sites) and disease location (worse PFS with liver or lung metastasis and left sided tumor) were associated with immunotherapy outcome in dMMR/MSI-H mCRC.
MeSH term(s)	Humans ; Male ; DNA Mismatch Repair ; Prospective Studies ; Colonic Neoplasms ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/therapy ; Immunotherapy ; Microsatellite Instability ; Brain Neoplasms ; Neoplastic Syndromes, Hereditary
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2023.113495
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 583: Show issues

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Article: Concomitant diagnosis of endometrial and breast cancer - does the sequence matters?

Stern, Tomer / Peleg Hasson, Shira / Saad, Akram / Levanon, Keren / Michaan, Nadav / Laskov, Ido / Wolf, Ido / Safra, Tamar

Gynecologic oncology reports

2021 Volume 38, Page(s) 100863

Abstract: Objective: To examine whether patients with both breast cancer (BC) and endometrial cancer (EC) have different features of disease, and whether the sequence of appearance of these tumors is correlated with a more aggressive course.: Methods: A ... ...

Abstract	Objective: To examine whether patients with both breast cancer (BC) and endometrial cancer (EC) have different features of disease, and whether the sequence of appearance of these tumors is correlated with a more aggressive course. Methods: A retrospective, multi-center observational cohort study of patients treated in two tertiary medical centers between 2014 and 2020. Files of patients who had a co-diagnosis of BC and EC were reviewed and clinical, epidemiological, pathological and genetic characteristics were collected. Results: 67 patients with a co-diagnosis of both malignances were divided into two groups according to primary tumor diagnosis: BC first group (43/67, 64%) and EC first group (24/67, 36%). The time interval between diagnosis of malignancies was significantly longer in the BC first group (mean 144.5 months vs. 67 months, p < 0.05). BRCA mutations were found in higher numbers in the BC first group (27.5% vs. 9.5%, p = 0.18). A significantly higher number of patients in the BC first group had uterine serous carcinoma (USC) histology (44% vs. 12.5%, p < 0.05). This was independent of tamoxifen usage among patients (OR 0.65, 95% CI 0.17-2.49). Conclusions: In patients suffering from both BC and EC, the sequence of occurrence of malignancies has relevance: When EC presents as a second primary tumor, it tends to present in a more aggressive form, independent of previous tamoxifen use. The time interval between the diagnosis of malignancies was significantly longer in this group, offering an opportunity to improve preventive measures to decrease the likelihood of a subsequent lethal second cancer.
Language	English
Publishing date	2021-09-20
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2818505-5
ISSN	2352-5789
ISSN	2352-5789
DOI	10.1016/j.gore.2021.100863
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Article ; Online: CCNE1 expression in high grade serous carcinoma does not correlate with chemoresistance.

Sapoznik, Stav / Aviel-Ronen, Sarit / Bahar-Shany, Keren / Zadok, Oranit / Levanon, Keren

Oncotarget

2017 Volume 8, Issue 37, Page(s) 62240–62247

Abstract: Delayed diagnosis of ovarian cancer, as well as high recurrence rates and lack of personalized therapy options, are among the causes for poor survival figures. Much effort is made towards developing new therapeutic possibilities, however predictive ... ...

Abstract	Delayed diagnosis of ovarian cancer, as well as high recurrence rates and lack of personalized therapy options, are among the causes for poor survival figures. Much effort is made towards developing new therapeutic possibilities, however predictive biomarkers are still unavailable. CCNE1 amplification, occurring in ∼20% of the high grade serous ovarian tumors, was previously proposed as a marker for platinum resistance and poor prognosis as well as for CDK2 inhibition. The current study aimed to examine the role of CCNE1 positive-immunostain as a predictor of first-line taxane-platinum chemoresistance. We evaluated matched pre- vs. post-neoadjuvant chemotherapy tumor samples and correlated the degree of pathological response to treatment with CCNE1 expression levels. Our results indicate that CCNE1 immunohistochemistry does not predict taxane-platinum chemoresistance in ovarian cancer patients. Further research is required in order to enable personalized adjuvant treatment, in cases where poor pathological response is achieved after the neoadjuvant phase.
Language	English
Publishing date	2017-07-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.19272
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Article: Erdafitinib treatment in metastatic urothelial carcinoma: a real-world analysis.

Frontiers in oncology

2023 Volume 13, Page(s) 1151701

Abstract: Background: Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It was approved based on a phase 2 clinical ... ...

Abstract	Background: Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It was approved based on a phase 2 clinical trial, revealing a 40% response rate, and 13.8 months overall survival. These FGFR genomic alterations are uncommon. Thus, real-world data on erdafitinb use is scant. We herein describe erdafitinib treatment outcome in a real world patient cohort. Methods: We retrospectively reviewed the data of patients treated with erdafitinib from 9 Israeli medical centers. Results: Twenty-five patients with metastatic urothelial carcinoma (median age 73, 64% male, 80% with visceral metastases) were treated with erdafitinib between January 2020 to October 2022. A clinical benefit (complete response 12%, partial response 32%, stable disease 12%) was seen in 56%. Median progression-free survival was 2.7 months, and median overall survival 6.73 months. Treatment related toxicity ≥ grade 3 occurred in 52%, and 32% discontinued therapy due to adverse events. Conclusions: Erdafitinib therapy is associated with a clinical benefit in the real world setting, and associated with similar toxicity as reported in prospective clinical trials.
Language	English
Publishing date	2023-05-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1151701
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Article ; Online: Targeting autocrine amphiregulin robustly and reproducibly inhibits ovarian cancer in a syngeneic model: roles for wildtype p53.

Lindzen, Moshit / Ghosh, Soma / Noronha, Ashish / Drago, Diana / Nataraj, Nishanth Belugali / Leitner, Orith / Carvalho, Silvia / Zmora, Einav / Sapoznik, Stav / Shany, Keren Bahar / Levanon, Keren / Aderka, Dan / Ramírez, Belinda Sánchez / Dahlhoff, Maik / McNeish, Iain / Yarden, Yosef

Oncogene

2021 Volume 40, Issue 21, Page(s) 3665–3679

Abstract: Ovarian cancer (OvCA) remains one of the most devastating malignancies, but treatment options are still limited. We report that amphiregulin (AREG) can serve as an effective and safe pharmacological target in a syngeneic murine model. AREG is highly ... ...

Abstract	Ovarian cancer (OvCA) remains one of the most devastating malignancies, but treatment options are still limited. We report that amphiregulin (AREG) can serve as an effective and safe pharmacological target in a syngeneic murine model. AREG is highly abundant in abdominal fluids of patients with advanced OvCa. In immunocompetent animals, depletion or overexpression of AREG respectively prolonged or shortened animal survival. A new antibody we generated in AREG-knockout mice recognized murine AREG and reproducibly prolonged animal survival in the syngeneic model. The underlying mechanism likely involves binding of wildtype p53 to AREG's promoter and autocrine activation of the epidermal growth factor receptor (EGFR), a step blocked by the antibody. Accordingly, depletion of p53 downregulated AREG secretion and conferred tolerance, whereas blocking an adaptive process involving CXCL1, which transactivates EGFR, might increase therapeutic efficacy. Consistent with these observations, analysis of OvCa patients revealed that high AREG correlates with poor prognosis of patients expressing wildtype TP53. In conclusion, clinical tests of the novel antibody are warranted; high AREG, normal TP53, and reduced CXCL1 activity might identify patients with OvCa who may derive therapeutic benefit.
MeSH term(s)	Amphiregulin/metabolism ; Animals ; Antibodies, Monoclonal/pharmacology ; Autocrine Communication ; Biomarkers, Tumor/metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Nude ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Survival Rate ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	AREG protein, human ; Amphiregulin ; Antibodies, Monoclonal ; Areg protein, mouse ; Biomarkers, Tumor ; TP53 protein, human ; Tumor Suppressor Protein p53
Language	English
Publishing date	2021-04-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-021-01784-8
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