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Article: CAR-T Cell Therapy in Ovarian Cancer: Where Are We Now?

Cutri-French, Clare / Nasioudis, Dimitrios / George, Erin / Tanyi, Janos L

2024 Volume 14, Issue 8

Abstract: The success of chimeric antigen receptor T-cell (CAR-T) therapies in the treatment of hematologic malignancies has led to the investigation of their potential in the treatment of solid tumors, including ovarian cancer. While the immunosuppressive ... ...

Abstract	The success of chimeric antigen receptor T-cell (CAR-T) therapies in the treatment of hematologic malignancies has led to the investigation of their potential in the treatment of solid tumors, including ovarian cancer. While the immunosuppressive microenvironment of ovarian cancer has been a barrier in their implementation, several early phase clinical trials are currently evaluating CAR-T cell therapies targeting mesothelin, folate receptor a, HER2, MUC16, and B7H3. Ongoing challenges include cytokine-associated and "on-target, off-tumor" toxicities, while most common adverse events include cytokine release syndrome, hemophagocytic lymphohistiocytosis/macrophage activation-like syndrome (HLH/MAS), and neurotoxicity. In the present review, we summarize the current status of CAR-T therapy in ovarian cancer and discuss future directions.
Language	English
Publishing date	2024-04-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics14080819
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Article: Controversies in the Staging of Patients with Locally Advanced Cervical Cancer.

Nasioudis, Dimitrios / George, Erin M / Tanyi, Janos L

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 10

Abstract: Approximately 10-25% of patients with locally advanced cervical cancer harbor metastases to the para-aortic lymph nodes. Staging of patients with locally advanced cervical cancer can be performed with imaging techniques, such as PET-CT; however, false ... ...

Abstract	Approximately 10-25% of patients with locally advanced cervical cancer harbor metastases to the para-aortic lymph nodes. Staging of patients with locally advanced cervical cancer can be performed with imaging techniques, such as PET-CT; however, false negative rates can be as high as 20%, especially for patients with pelvic lymph node metastases. Surgical staging can identify patients with microscopic lymph nodes metastases and aid in accurate treatment planning with the administration of extended-field radiation therapy. Data from retrospective studies investigating the impact of para-aortic lymphadenectomy on the oncological outcomes of patients with locally advanced cervical cancer are mixed, while data from randomized controlled trials do not demonstrate a progression-free survival benefit. In the present review, we explore controversies in the staging of patients with locally advanced cervical cancer and summarize the available literature.
Language	English
Publishing date	2023-05-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13101747
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Article ; Online: Personalized vaccination against ovarian cancer: what are the possibilities?

Tanyi, Janos L / George, Erin

Expert review of vaccines

2018 Volume 17, Issue 11, Page(s) 955–958

MeSH term(s)	Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Female ; Humans ; Immunotherapy/methods ; Ovarian Neoplasms/immunology ; Ovarian Neoplasms/therapy ; Precision Medicine/methods ; Vaccination/methods
Chemical Substances	Cancer Vaccines
Language	English
Publishing date	2018-11-07
Publishing country	England
Document type	Editorial
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1080/14760584.2018.1541743
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Zs.A 6077: Show issues

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Article ; Online: Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study.

Wagner, Patrick / Levine, Edward A / Kim, Alex C / Shen, Perry / Fleming, Nicole D / Westin, Shannon N / Berry, Laurel K / Karakousis, Giorgos C / Tanyi, Janos L / Olson, Madeline T / Madajewski, Brian / Ostrander, Brian / Krishnan, Kartik / Balch, Charles M / Bartlett, David L

Annals of surgical oncology

2024

Abstract: Background: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. ... ...

Abstract	Background: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS. Patients and methods: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance. Results: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients. Conclusions: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1200469-8
ISSN	1534-4681 ; 1068-9265
ISSN (online)	1534-4681
ISSN	1068-9265
DOI	10.1245/s10434-024-15165-4
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Zs.A 4042: Show issues

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Article: Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study.

Ghezelayagh, Talayeh S / Wu, Emily S / Barber, Emma L / Dao, Minh D / Zsiros, Emese / Urban, Renata R / Gray, Heidi J / Goff, Barbara A / Shah, Chirag A / Neubauer, Nikki L / Dai, James Y / Tanyi, Janos L / Liao, John B

European journal of gynaecological oncology

2023 Volume 44, Issue 1, Page(s) 17–25

Abstract: Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has ... ...

Abstract	Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34,
Language	English
Publishing date	2023-02-14
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	604589-3
ISSN	0392-2936
ISSN	0392-2936
DOI	10.22514/ejgo.2023.002
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Zs.A 1679: Show issues

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Article ; Online: Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results.

Hassan, Raffit / Butler, Marcus / O'Cearbhaill, Roisin E / Oh, David Y / Johnson, Melissa / Zikaras, Kevin / Smalley, Munisha / Ross, Michael / Tanyi, Janos L / Ghafoor, Azam / Shah, Nirali N / Saboury, Babak / Cao, Liang / Quintás-Cardama, Alfonso / Hong, David

Nature medicine

2023 Volume 29, Issue 8, Page(s) 2099–2109

Abstract: The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon ... ...

Abstract	The T cell receptor fusion construct (TRuC) gavocabtagene autoleucel (gavo-cel) consists of single-domain anti-mesothelin antibody that integrates into the endogenous T cell receptor (TCR) and engages the signaling capacity of the entire TCR upon mesothelin binding. Here we describe phase 1 results from an ongoing phase1/2 trial of gavo-cel in patients with treatment-refractory mesothelin-expressing solid tumors. The primary objectives were to evaluate safety and determine the recommended phase 2 dose (RP2D). Secondary objectives included efficacy. Thirty-two patients received gavo-cel at increasing doses either as a single agent (n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 10
MeSH term(s)	Humans ; Neoplasms/therapy ; Neoplasms/drug therapy ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/therapeutic use ; Cell- and Tissue-Based Therapy
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-07-27
Publishing country	United States
Document type	Clinical Trial, Phase II ; Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-023-02452-y
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 39: Show issues

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Article ; Online: A retrospective case series of Mohs micrographic surgery and interdisciplinary management of female genital skin cancers: Local recurrence rates and patient-reported outcomes.

Nugent, Shannon T / Raj, Leela K / Latif, Nawar A / Cory, Lori / Tanyi, Janos L / Kovach, Stephen J / Fischer, John P / Fosnot, Joshua / Lin, Ines C / Etzkorn, Jeremy R / Shin, Thuzar M / Giordano, Cerrene N / Higgins, H William / Walker, Joanna L / Miller, Christopher J

Journal of the American Academy of Dermatology

2023 Volume 89, Issue 2, Page(s) 301–308

Abstract: Background: Conventional excision of female genital skin cancers has high rates of local recurrence and morbidity. Few publications describe local recurrence rates (LRRs) and patient-reported outcomes (PROs) after Mohs micrographic surgery (MMS) for ... ...

Abstract	Background: Conventional excision of female genital skin cancers has high rates of local recurrence and morbidity. Few publications describe local recurrence rates (LRRs) and patient-reported outcomes (PROs) after Mohs micrographic surgery (MMS) for female genital skin cancers. Objective: To evaluate LRRs, PROs, and interdisciplinary care after MMS for female genital skin cancers. Methods: A retrospective case series was conducted of female genital skin cancers treated with MMS between 2006 and 2021 at an academic center. The primary outcome was local recurrence. Secondary outcomes were PROs and details of interdisciplinary care. Results: Sixty skin cancers in 57 patients were treated with MMS. Common diagnoses included squamous cell cancer (n = 26), basal cell cancer (n = 12), and extramammary Paget disease (n = 11). Three local recurrences were detected with a mean follow-up of 61.1 months (median: 48.8 months). Thirty-one patients completed the PROs survey. Most patients were satisfied with MMS (71.0%, 22/31) and reported no urinary incontinence (93.5%, 29/31). Eight patients were sexually active at follow-up and 75.0% (6/8) experienced no sexual dysfunction. Most cases involved interdisciplinary collaboration 71.7% (43/60). Limitations: Limitations include the retrospective single-center design, heterogeneous cohort, and lack of preoperative function data. Conclusions: Incorporating MMS into interdisciplinary teams may help achieve low LRRs and satisfactory function after genital skin cancer surgery.
MeSH term(s)	Humans ; Female ; Mohs Surgery ; Retrospective Studies ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Recurrence, Local/surgery ; Skin Neoplasms/surgery ; Genitalia, Female/surgery
Language	English
Publishing date	2023-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	603641-7
ISSN	1097-6787 ; 0190-9622
ISSN (online)	1097-6787
ISSN	0190-9622
DOI	10.1016/j.jaad.2023.02.050
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Zs.A 1540: Show issues

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Article ; Online: H2Bub1 loss is an early contributor to clear cell ovarian cancer progression.

Ferrari, Adam J / Rawat, Priyanka / Rendulich, Hannah S / Annapragada, Akshaya V / Kinose, Yasuto / Zhang, Xiaoming / Devins, Kyle / Budina, Anna / Scharpf, Robert B / Mitchell, Marilyn A / Tanyi, Janos L / Morgan, Mark A / Schwartz, Lauren E / Soong, T Rinda / Velculescu, Victor E / Drapkin, Ronny

JCI insight

2023 Volume 8, Issue 12

Abstract: Epigenetic aberrations, including posttranslational modifications of core histones, are major contributors to cancer. Here, we define the status of histone H2B monoubiquitylation (H2Bub1) in clear cell ovarian carcinoma (CCOC), low-grade serous carcinoma, ...

Abstract	Epigenetic aberrations, including posttranslational modifications of core histones, are major contributors to cancer. Here, we define the status of histone H2B monoubiquitylation (H2Bub1) in clear cell ovarian carcinoma (CCOC), low-grade serous carcinoma, and endometrioid carcinomas. We report that clear cell carcinomas exhibited profound loss, with nearly all cases showing low or negative H2Bub1 expression. Moreover, we found that H2Bub1 loss occurred in endometriosis and atypical endometriosis, which are established precursors to CCOCs. To examine whether dysregulation of a specific E3 ligase contributes to the loss of H2Bub1, we explored expression of ring finger protein 40 (RNF40), ARID1A, and UBR7 in the same case cohort. Loss of RNF40 was significantly and profoundly correlated with loss of H2Bub1. Using genome-wide DNA methylation profiles of 230 patients with CCOC, we identified hypermethylation of RNF40 in CCOC as a likely mechanism underlying the loss of H2Bub1. Finally, we demonstrated that H2Bub1 depletion promoted cell proliferation and clonogenicity in an endometriosis cell line. Collectively, our results indicate that H2Bub1 plays a tumor-suppressive role in CCOCs and that its loss contributes to disease progression.
MeSH term(s)	Female ; Humans ; Endometriosis/genetics ; Histones/genetics ; Carcinoma ; Peritoneal Neoplasms ; Ovarian Neoplasms/genetics
Chemical Substances	Histones
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.164995
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Article ; Online: Correction: Identification of Novel Pathogenic Sequence Variants of the Mismatch Repair Genes During Screening for Lynch Syndrome in a Single Centre of Eastern Hungary.

Kóder, Gergely / Olasz, Judit / Tanyi, Janos L / George, Erin / Tóth, László / Antal-Szalmás, Péter / Nagy, Béla / Bubán, Tamás / András, Csilla / Urbancsek, Hilda / Laczik, Miklós / Csuka, Orsolya / Damjanovich, László / Tanyi, Miklós

Journal of gastrointestinal cancer

2020 Volume 51, Issue 3, Page(s) 1016–1017

Abstract: The original version of this article unfortunately contained a mistake. The variants listed in Table 3 of the original version of this article are not in line with the latest HGVS (Human Genome Variation Society) nomenclature (version 19.01). ...

Abstract	The original version of this article unfortunately contained a mistake. The variants listed in Table 3 of the original version of this article are not in line with the latest HGVS (Human Genome Variation Society) nomenclature (version 19.01).
Language	English
Publishing date	2020-03-24
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2452514-5
ISSN	1941-6636 ; 1559-0739 ; 1941-6628 ; 1537-3649
ISSN (online)	1941-6636 ; 1559-0739
ISSN	1941-6628 ; 1537-3649
DOI	10.1007/s12029-020-00398-9
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Zs.A 2184: Show issues

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Article ; Online: Systematic illumination of druggable genes in cancer genomes.

Jiang, Junjie / Yuan, Jiao / Hu, Zhongyi / Zhang, Youyou / Zhang, Tianli / Xu, Mu / Long, Meixiao / Fan, Yi / Tanyi, Janos L / Montone, Kathleen T / Tavana, Omid / Vonderheide, Robert H / Chan, Ho Man / Hu, Xiaowen / Zhang, Lin

Cell reports

2022 Volume 38, Issue 8, Page(s) 110400

Abstract: By combining 6 druggable genome resources, we identify 6,083 genes as potential druggable genes (PDGs). We characterize their expression, recurrent genomic alterations, cancer dependencies, and therapeutic potentials by integrating genome, functionome, ... ...

Abstract	By combining 6 druggable genome resources, we identify 6,083 genes as potential druggable genes (PDGs). We characterize their expression, recurrent genomic alterations, cancer dependencies, and therapeutic potentials by integrating genome, functionome, and druggome profiles across cancers. 81.5% of PDGs are reliably expressed in major adult cancers, 46.9% show selective expression patterns, and 39.1% exhibit at least one recurrent genomic alteration. We annotate a total of 784 PDGs as dependent genes for cancer cell growth. We further quantify 16 cancer-related features and estimate a PDG cancer drug target score (PCDT score). PDGs with higher PCDT scores are significantly enriched for genes encoding kinases and histone modification enzymes. Importantly, we find that a considerable portion of high PCDT score PDGs are understudied genes, providing unexplored opportunities for drug development in oncology. By integrating the druggable genome and the cancer genome, our study thus generates a comprehensive blueprint of potential druggable genes across cancers.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Genome ; Genomics ; Humans ; Lighting ; Neoplasms/drug therapy ; Neoplasms/genetics
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2022-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110400
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