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Article ; Online: Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer.

Stefanoudakis, Dimitrios / Frountzas, Maximos / Schizas, Dimitrios / Michalopoulos, Nikolaos V / Drakaki, Alexandra / Toutouzas, Konstantinos G

Current issues in molecular biology

2024 Volume 46, Issue 4, Page(s) 2827–2844

Abstract: The present review demonstrates the major tumor suppressor genes, including TP53, CDKN2A and SMAD4, associated with pancreatic cancer. Each gene's role, prevalence and impact on tumor development and progression are analyzed, focusing on the intricate ... ...

Abstract	The present review demonstrates the major tumor suppressor genes, including TP53, CDKN2A and SMAD4, associated with pancreatic cancer. Each gene's role, prevalence and impact on tumor development and progression are analyzed, focusing on the intricate molecular landscape of pancreatic cancer. In addition, this review underscores the prognostic significance of specific mutations, such as loss of TP53, and explores some potential targeted therapies tailored to these molecular signatures. The findings highlight the importance of genomic analyses for risk assessment, early detection and the design of personalized treatment approaches in pancreatic cancer. Overall, this review provides a comprehensive analysis of the molecular intricacies of pancreatic tumors, paving the way for more effective and tailored therapeutic interventions.
Language	English
Publishing date	2024-03-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2000024-8
ISSN	1467-3045 ; 1467-3037
ISSN (online)	1467-3045
ISSN	1467-3037
DOI	10.3390/cimb46040177
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Article: Treatment Equity in the Immunotherapy Era: Options for Patients with Both Autoimmune Disease and GU Cancers.

Hui, Gavin / Drolen, Claire / Hannigan, Christopher A / Drakaki, Alexandra

Life (Basel, Switzerland)

2022 Volume 12, Issue 3

Abstract: Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune- ... ...

Abstract	Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune-related adverse events (irAEs). The scope of irAEs is broad, and this paper aims to review the rheumatologic side effects associated with immunotherapy drugs approved for bladder cancer and renal cell carcinoma. IrAEs are graded by the common terminology criteria for adverse events (CTCAE), which ranges from 1 to 5. The management of irAEs includes corticosteroids or other immunosuppressive therapies, and it may require discontinuation of immunotherapy. Several real world experience studies suggest that most patients with pre-existing autoimmune diseases treated with ICI did not have to discontinue treatment due to immune-mediated side effects. While data suggest autoimmune side effects are manageable, patients with pre-existing autoimmune diseases are often excluded from immunotherapy clinical trials. Better understanding of these irAEs will improve its safety and expand its use in those with underlying autoimmune disease.
Language	English
Publishing date	2022-03-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12030360
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Article ; Online: Immunotherapy and Metastatic Renal Cell Carcinoma

Nikhita Kathuria-Prakash / Claire Drolen / Christopher A. Hannigan / Alexandra Drakaki

Life, Vol 12, Iss 24, p

A Review of New Treatment Approaches

2022 Volume 24

Abstract: Introduction: Renal cell carcinomas (RCC) have been treated with immunotherapy for decades; the use of immune checkpoint inhibitors represents the most recent advance. In this review, we compare these new RCC immunotherapies, with a focus on achieving ... ...

Abstract	Introduction: Renal cell carcinomas (RCC) have been treated with immunotherapy for decades; the use of immune checkpoint inhibitors represents the most recent advance. In this review, we compare these new RCC immunotherapies, with a focus on achieving durable complete responses (CR). Review: Sorafenib and sunitinib were the first Food and Drug Administration (FDA)-approved targeted agents for RCC, with sunitinib eventually becoming the standard-of-care agent against which novel therapies are compared. In the last five years, many combination therapies based on the use of immune checkpoint inhibitors (ICIs) and receptor tyrosine kinase inhibitors (TKIs), including ipilimumab/nivolumab, nivolumab/cabozantinib, avelumab/axitinib, pembrolizumab/axitinib, and pembrolizumab/lenvatinib, have demonstrated superior overall survival (OS) and progression-free survival (PFS) compared to sunitinib. Ongoing clinical trials of hypoxia-induced factor-2 alpha (HIF-2a) inhibitors, chimeric antigen receptor T cell (CAR-T) therapy targeting CD70, and other new combination therapies have also shown promise and are currently under investigation. Conclusions: Many new combination therapies are approved for RCC treatment, and CR rates suggest that, in the era of immunotherapy, it may be possible to achieve durable responses and survival benefit in patients with metastatic RCC.
Keywords	renal cell carcinoma ; immunotherapy ; immune checkpoint inhibitors ; sunitinib ; complete response rate ; Science ; Q
Subject code	616
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Treatment Equity in the Immunotherapy Era

Gavin Hui / Claire Drolen / Christopher A. Hannigan / Alexandra Drakaki

Life, Vol 12, Iss 360, p

Options for Patients with Both Autoimmune Disease and GU Cancers

2022 Volume 360

Abstract	Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune-related adverse events (irAEs). The scope of irAEs is broad, and this paper aims to review the rheumatologic side effects associated with immunotherapy drugs approved for bladder cancer and renal cell carcinoma. IrAEs are graded by the common terminology criteria for adverse events (CTCAE), which ranges from 1 to 5. The management of irAEs includes corticosteroids or other immunosuppressive therapies, and it may require discontinuation of immunotherapy. Several real world experience studies suggest that most patients with pre-existing autoimmune diseases treated with ICI did not have to discontinue treatment due to immune-mediated side effects. While data suggest autoimmune side effects are manageable, patients with pre-existing autoimmune diseases are often excluded from immunotherapy clinical trials. Better understanding of these irAEs will improve its safety and expand its use in those with underlying autoimmune disease.
Keywords	immune checkpoint inhibitors ; autoimmune disease ; renal cancer ; bladder cancer ; immune-related adverse event ; immunotherapy ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Immunotherapy and Metastatic Renal Cell Carcinoma: A Review of New Treatment Approaches.

Kathuria-Prakash, Nikhita / Drolen, Claire / Hannigan, Christopher A / Drakaki, Alexandra

Life (Basel, Switzerland)

2021 Volume 12, Issue 1

Abstract	Introduction: Renal cell carcinomas (RCC) have been treated with immunotherapy for decades; the use of immune checkpoint inhibitors represents the most recent advance. In this review, we compare these new RCC immunotherapies, with a focus on achieving durable complete responses (CR). Review: Sorafenib and sunitinib were the first Food and Drug Administration (FDA)-approved targeted agents for RCC, with sunitinib eventually becoming the standard-of-care agent against which novel therapies are compared. In the last five years, many combination therapies based on the use of immune checkpoint inhibitors (ICIs) and receptor tyrosine kinase inhibitors (TKIs), including ipilimumab/nivolumab, nivolumab/cabozantinib, avelumab/axitinib, pembrolizumab/axitinib, and pembrolizumab/lenvatinib, have demonstrated superior overall survival (OS) and progression-free survival (PFS) compared to sunitinib. Ongoing clinical trials of hypoxia-induced factor-2 alpha (HIF-2a) inhibitors, chimeric antigen receptor T cell (CAR-T) therapy targeting CD70, and other new combination therapies have also shown promise and are currently under investigation. Conclusions: Many new combination therapies are approved for RCC treatment, and CR rates suggest that, in the era of immunotherapy, it may be possible to achieve durable responses and survival benefit in patients with metastatic RCC.
Language	English
Publishing date	2021-12-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662250-6
ISSN	2075-1729
ISSN	2075-1729
DOI	10.3390/life12010024
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Article ; Online: Prognostic Value of End-of-Treatment PSMA PET/CT in Patients Treated with

Murthy, Vishnu / Gafita, Andrei / Thin, Pan / Nguyen, Kathleen / Grogan, Tristan / Shen, John / Drakaki, Alexandra / Rettig, Matthew / Czernin, Johannes / Calais, Jeremie

Journal of nuclear medicine : official publication, Society of Nuclear Medicine

2023 Volume 64, Issue 11, Page(s) 1737–1743

Abstract: Our objective was to evaluate the prognostic value of end-of-treatment prostate-specific membrane antigen (PSMA) PET/CT (PSMA-PET) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated ... ...

Abstract	Our objective was to evaluate the prognostic value of end-of-treatment prostate-specific membrane antigen (PSMA) PET/CT (PSMA-PET) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with
MeSH term(s)	Humans ; Male ; Heterocyclic Compounds, 1-Ring/therapeutic use ; Lutetium/therapeutic use ; Positron Emission Tomography Computed Tomography ; Prognosis ; Prospective Studies ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/diagnostic imaging ; Prostatic Neoplasms, Castration-Resistant/radiotherapy ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Retrospective Studies ; Treatment Outcome
Chemical Substances	Heterocyclic Compounds, 1-Ring ; Lutetium (5H0DOZ21UJ) ; Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2023-09-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	80272-4
ISSN	1535-5667 ; 0097-9058 ; 0161-5505 ; 0022-3123
ISSN (online)	1535-5667
ISSN	0097-9058 ; 0161-5505 ; 0022-3123
DOI	10.2967/jnumed.122.265155
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Zs.A 114: 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 328: Show issues

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Article ; Online: Gain of Chromosome 5q Predicts a Favorable Prognosis in Localized Renal Cell Carcinoma.

Lebacle, Cedric / Pooli, Aydin / Shuch, Brian / Rao, Nagesh / Chamie, Karim / Kroeger, Nils / Faiena, Izak / Liu, Sandy / Wood, Erika L / Belldegrun, Arie / Drakaki, Alexandra / Pantuck, Allan J

Cancer investigation

2024 Volume 42, Issue 1, Page(s) 97–103

Abstract: Approximately 65% of renal cell carcinomas (RCC) are diagnosed at a localized stage. We investigated the chromosome 5q gain impact on disease-free survival (DFS) in RCC patients. Overall, 676 patients with stages 1-2 RCC and having cytogenetic analysis ... ...

Abstract	Approximately 65% of renal cell carcinomas (RCC) are diagnosed at a localized stage. We investigated the chromosome 5q gain impact on disease-free survival (DFS) in RCC patients. Overall, 676 patients with stages 1-2 RCC and having cytogenetic analysis were included. Gain of 5q was observed in 108 patients, more frequently in clear cell (ccRCC) than non-clear cell tumors. Gain of 5q is likely an independent prognostic factor since the concerned patients had a decreased recurrence risk in stages 1-2 RCC, confirmed in multivariable analysis. Detecting 5q gain could enhance recurrence risk assessment, allowing tailored post-surgery surveillance, and reducing unnecessary treatments.
MeSH term(s)	Humans ; Carcinoma, Renal Cell/genetics ; Kidney Neoplasms/genetics ; Prognosis ; Disease-Free Survival ; Chromosomes
Language	English
Publishing date	2024-02-05
Publishing country	England
Document type	Journal Article
ZDB-ID	604942-4
ISSN	1532-4192 ; 0735-7907
ISSN (online)	1532-4192
ISSN	0735-7907
DOI	10.1080/07357907.2024.2308172
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Zs.A 1862: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Do Cancer Genetics Impact Treatment Decision Making? Immunotherapy and Beyond in the Management of Advanced and Metastatic Urothelial Carcinoma.

Hui, Gavin / Stefanoudakis, Dimitrios / Zektser, Yuliya / Isaacs, Dayna Jill / Hannigan, Christopher / Pantuck, Allan J / Drakaki, Alexandra

Current oncology (Toronto, Ont.)

2023 Volume 30, Issue 8, Page(s) 7398–7411

Abstract: Bladder cancer is one of the most commonly diagnosed genitourinary malignancies. For many years, the primary treatment for metastatic urothelial cancer (mUC) was predicated on the use of platinum-based chemotherapy. More recently, immune checkpoint ... ...

Abstract	Bladder cancer is one of the most commonly diagnosed genitourinary malignancies. For many years, the primary treatment for metastatic urothelial cancer (mUC) was predicated on the use of platinum-based chemotherapy. More recently, immune checkpoint inhibitors (ICIs) were approved by regulatory agencies such as the US FDA for use in both the first- and second-line settings. This review outlines the approved ICIs for mUC in the second-line setting and as an alternative to chemotherapy in the first-line setting, as well as the novel agents that have also been incorporated into the treatment of this malignancy. Single-agent ICIs are often used in second-line settings in mUC, and there are three drugs currently approved for those who progress after receiving platinum-based chemotherapy. In the first-line setting, the preferred treatment regimen remains cisplatin-based chemotherapy. However, single-agent ICI can be an alternative first-line treatment for those who are not candidates for cisplatin-based therapy. There are also clinical trials adding ICIs to chemotherapy as combination regimens. However, treatment for mUC has now expanded even beyond immunotherapy. Newer targeted agents such as erdafitinib, a fibroblast growth factor receptor inhibitor, and two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been recently approved. As new drug agents are discovered, it will be important to assess both the treatment outcomes as well as the effects on patients' quality of life. Furthermore, integrating genetic and molecular information can help guide treatment decisions as next-generation sequencing is more commonly acquired during the evaluation of newly diagnosed patients with advanced and metastatic cancer.
MeSH term(s)	Humans ; Carcinoma, Transitional Cell ; Cisplatin ; Quality of Life ; Urinary Bladder Neoplasms ; Immunotherapy ; Decision Making
Chemical Substances	Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2023-08-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1236972-x
ISSN	1718-7729 ; 1198-0052
ISSN (online)	1718-7729
ISSN	1198-0052
DOI	10.3390/curroncol30080536
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Article: Safety and efficacy of immune checkpoint inhibitor cancer therapy in patients with preexisting type 1 diabetes mellitus.

Hilder, Robin / Tsai, Karen / Quandt, Zoe / Isaacs, Dayna / Drakaki, Alexandra / Xing, Yan / In, Gino K / Angell, Trevor E / Lechner, Melissa G

Frontiers in endocrinology

2023 Volume 14, Page(s) 1242830

Abstract: Introduction: Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of ... ...

Abstract	Introduction: Immune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM. Methods: This retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class. Results: Of 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2-3.56), p = 0.81, and OR 1.69 (0.31-9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy. Discussion: These data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.
MeSH term(s)	Adult ; Humans ; Female ; Middle Aged ; Male ; Immune Checkpoint Inhibitors/adverse effects ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/drug therapy ; Diabetes Mellitus, Type 1/chemically induced ; Retrospective Studies ; Prospective Studies ; Antineoplastic Agents, Immunological/adverse effects ; Neoplasms/complications ; Neoplasms/drug therapy ; Neoplasms/pathology ; Autoimmune Diseases/complications
Chemical Substances	Immune Checkpoint Inhibitors ; Antineoplastic Agents, Immunological
Language	English
Publishing date	2023-10-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1242830
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Article ; Online: To treat or not to treat: Patient exclusion in immune oncology clinical trials due to preexisting autoimmune disease.

Pantuck, Morgan / McDermott, David / Drakaki, Alexandra

Cancer

2019 Volume 125, Issue 20, Page(s) 3506–3513

Abstract: Newly developed immune checkpoint inhibitors (ICIs) demonstrate impressive clinical activity. However, they can also cause life-threatening side effects. The efficacy and toxicity associated with ICIs both derive from unregulated, enhanced immune ... ...

Abstract	Newly developed immune checkpoint inhibitors (ICIs) demonstrate impressive clinical activity. However, they can also cause life-threatening side effects. The efficacy and toxicity associated with ICIs both derive from unregulated, enhanced immune activation. Health care providers have been hesitant to prescribe these medications to patients who have preexisting autoimmune disease (AD) because of concerns that this may exacerbate their underlying immune condition. These patients have also been excluded from ongoing ICI clinical trials. However, new data suggest that the potential benefits of ICI treatment may outweigh the potential risks for this patient group as long as physicians also provide sufficient monitoring for AD exacerbations or other side effects. Therefore, it may be appropriate to include patients with advanced malignancies and preexisting AD in ICI clinical trials when no other effective cancer treatment options exist. Overall, physicians should avoid excluding patients from ICI therapy unnecessarily when the potential benefits outweigh the potential risks.
MeSH term(s)	Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Autoimmune Diseases/complications ; Autoimmune Diseases/epidemiology ; Autoimmune Diseases/immunology ; Autoimmune Diseases/therapy ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/immunology ; CTLA-4 Antigen/antagonists & inhibitors ; CTLA-4 Antigen/immunology ; Clinical Trials as Topic ; Humans ; Immunotherapy/adverse effects ; Neoplasms/complications ; Neoplasms/epidemiology ; Neoplasms/immunology ; Neoplasms/therapy
Chemical Substances	Antibodies, Monoclonal ; B7-H1 Antigen ; CTLA-4 Antigen
Language	English
Publishing date	2019-07-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.32326
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