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Article: Chimeric antigen receptors: unleashing a new age of anti-cancer therapy.

Leyfman, Yan

2018 Volume 18, Page(s) 182

Abstract: Background: Chimeric antigen receptors (CARs) represent a novel facet of modern day synthetic biology that exemplifies personalized medicine at work through their ability to harness and redirect a patient's immune system to fight cancer.: Body: By ... ...

Abstract	Background: Chimeric antigen receptors (CARs) represent a novel facet of modern day synthetic biology that exemplifies personalized medicine at work through their ability to harness and redirect a patient's immune system to fight cancer. Body: By combining the target-specificity of antibodies to the effector capabilities of T cells, CARs have yielded high remission rates for many late staged and relapsed/refractory (r/r) hematological malignancies, including acute lymphoblastic leukemias (ALL) and Non-Hodgkin's lymphomas. Despite toxicities of cytokine release syndrome and neurotoxicity, recent studies have uncovered their underlying mechanisms and devised effective therapies to manage and possibly prevent them. In 2017, CAR T cell therapy became a reality for the general public despite the high costs, when Novartis's Kymriah, became the first product to receive FDA approval for pediatric r/r B cell ALL with Gilead's Yescarta following several months later. Although effective in hematological malignancies, CAR response has been limited in solid tumors largely attributed to the heterogeneous and immunosuppressive tumor microenvironment along tumor defense mechanisms, such as antigenic escape. Conclusion: Despite the current challenges of CAR T therapy, this technology is still in its infancy and its promise will continue to grow as scientists continue to develop novel approaches to enhance its efficacy. As its prevalence continues to increase, institutions and pharmaceuticals worldwide are investing in this technology in hopes of driving therapeutic innovation, while providing greater access to their respective populations through clinical trials.
Language	English
Publishing date	2018-11-14
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2091573-1
ISSN	1475-2867
ISSN	1475-2867
DOI	10.1186/s12935-018-0685-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Innovations in Thoracic Oncology and the Promise of Liquid Biopsies with Dr. Luis Raez.

Cortiana, Viviana / Van de Kieft, Alexandra / Chorya, Harshal / Gambill, Jade / Park, Chandler H / Leyfman, Yan

Cancers

2024 Volume 16, Issue 4

Abstract: Thoracic oncology continues to pose a great threat to human health as one of the most common forms of cancer. Liquid biopsies present a transformative approach to treating patients affected by these types of diseases by providing a less invasive genetic ... ...

Abstract	Thoracic oncology continues to pose a great threat to human health as one of the most common forms of cancer. Liquid biopsies present a transformative approach to treating patients affected by these types of diseases by providing a less invasive genetic overview of the tumor, aiding in both diagnostic and treatment measures. The primary objective of this article is to examine the prospects of liquid biopsies in managing thoracic malignancies and to present barriers to their usage as demonstrated by Dr. Luis Raez. In examining why molecular diagnostics continue to be employed together with more traditional methods, this article presents the next steps in the clinical application of blood-based cancer screening. Future cancer diagnosis and treatment aim to prioritize circulating biomarker analyses based on their potential for the detection and monitoring of thoracic cancers. Liquid biopsies are favored thanks to their reduced invasiveness with respect to traditional treatments. The further study of clinical biomarkers and technological advancements are thus pivotal to enhance the clinical applicability of this method. In conclusion, this blood-based analysis offers a promising route by which the diagnosis, treatments, and outcomes of thoracic cancer can be improved.
Language	English
Publishing date	2024-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16040799
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Article: Reviewing the Landscape of Cancer Survivorship: Insights from Dr. Lidia Schapira's Programs and Beyond.

Cortiana, Viviana / Abbas, Rabab Hunaid / Nadar, Soumiya / Mahendru, Diksha / Gambill, Jade / Menon, Gayathri Pramil / Park, Chandler H / Leyfman, Yan

Cancers

2024 Volume 16, Issue 6

Abstract: The constantly escalating population of cancer survivors worldwide has prompted a focused exploration of their unique needs and experiences within the context of healthcare medicine. This review initiates its analysis inspired by Dr. Lidia Schapira's ... ...

Abstract	The constantly escalating population of cancer survivors worldwide has prompted a focused exploration of their unique needs and experiences within the context of healthcare medicine. This review initiates its analysis inspired by Dr. Lidia Schapira's insightful keynote conference on the Survivorship 1.0 and Survivorship 2.0 Programs, shedding light on their implementation challenges and setting the stage for a comprehensive analysis of cancer survivorship initiatives. Within the transformed landscape of cancer care, patient-centric strategies embedded in cancer survivorship programs comprising vital elements such as connection, support, and education are presented. While placing cancer recurrence surveillance at the forefront, the review underlines concern regarding the potential oversight of the enduring impact on mental and physical health. Dr. Schapira's insights further extend into the exploration of mental health challenges faced by survivors, promoting an examination of diverse strategies to address these concerns. Furthermore, the discussion continues toward promising areas of research, notably Precision Medicine's role in de-escalating cancer therapies, and advocates for measures such as early cancer awareness and timely referrals to supportive services. Highlighting the significance of education, the role of online resources in enhancing the knowledge of healthcare practitioners and future generations in cancer care is then explored. The paper concludes by presenting some of the most prominent global current survivorship programs, identifying critical knowledge gaps in cancer care and projecting future developments aimed at delivering accurate and holistic care, improving the quality of life for survivors, and enhancing both mental and physical well-being. Drawing upon the insights from Dr. Schapira, this review lays the groundwork for a nuanced exploration of cancer survivorship and its multifaceted implications.
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16061216
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Article: Cholangiocarcinoma Insights: Established Foundations and Cutting-Edge Innovations from Dr. James Cleary's Pioneering Research.

Cortiana, Viviana / Chorya, Harshal / Joshi, Muskan / Kannan, Shreevikaa / Mahendru, Diksha / Vallabhaneni, Harshitha / Coloma, Helena S / Leyfman, Yan / Park, Chandler H

Cancers

2024 Volume 16, Issue 3

Abstract: This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary ... ...

Abstract	This paper provides insights into the conventional understanding of biliary tract malignancies, with a specific focus on cholangiocarcinoma (CCA). We then delve into the groundbreaking ideas presented by Dr. James Cleary. CCA, originating from biliary tree cells, manifests diverse subtypes contingent upon anatomical localization and differentiation status. These variants exhibit discrete genetic aberrations, yielding disparate clinical phenotypes and therapeutic modalities. Intrahepatic, perihilar, and distal CCAs intricately involve distinct segments of the biliary tree, further categorized as well-differentiated, moderately differentiated, or poorly differentiated adenocarcinomas based on their histological differentiation. Understanding the etiological factors contributing to CCA development assumes paramount importance. Stratifying these factors into two groups, those unrelated to fluke infestations (e.g., viral hepatitis and fatty liver conditions) and those associated with fluke infestations (e.g., chronic liver inflammation), facilitates predictive modeling. The epidemiology of CCA exhibits global variability, with Southeast Asia notably displaying higher incidences attributed primarily to liver fluke infestations. Jaundice resulting from bile duct obstruction constitutes a prevalent clinical manifestation of CCA, alongside symptoms like malaise, weight loss, and abdominal pain. Diagnostic challenges arise due to the symptomatic overlap with other biliary disorders. Employing comprehensive liver function tests and imaging modalities such as computed tomography assumes a pivotal role in ensuring accurate diagnosis and staging. However, the definitive confirmation of CCA necessitates a biopsy. Treatment modalities, predominantly encompassing surgical resection and radiation therapy, hold curative potential, although a considerable subset of patients is deemed unresectable upon exploration. Challenges intensify, particularly in cases classified as cancer of unknown origin, underscoring the imperative for early intervention. Advancements in genomic sequencing have revolutionized precision medicine in CCA. Distinct genomic markers, including fibroblast growth factor receptor 2 (FGFR2) alterations and isocitrate dehydrogenase 1 (IDH1) mutations, have emerged as promising therapeutic targets. FGFR2 alterations, encompassing mutations and rearrangements, play pivotal roles in oncogenesis, with FGFR inhibitors demonstrating promise despite identified resistance mechanisms. Similarly, IDH1 inhibitors face challenges with resistance, despite encouraging early clinical trial results, prompting exploration of novel irreversible inhibitors. Dr. James Cleary's illuminating discourse underscores the significance of diverse FGFR2 alterations and the potential of IDH1 inhibition in reshaping the treatment landscape for CCA. These findings unveil critical avenues for targeted therapeutic interventions, emphasizing the critical need for ongoing research to optimize outcomes in this challenging cancer subtype, incorporating innovative insights from Dr. Cleary.
Language	English
Publishing date	2024-02-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16030632
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Article ; Online: Extracellular vesicles: A promising therapy against SARS-CoV-2 infection.

Leyfman, Yan / Gohring, Greta / Joshi, Muskan / Menon, Gayathri Pramil / Van de Kieft, Alexandra / Rivero, Tania Del / Bellio, Michael A / Mitrani, Maria Ines

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 5, Page(s) 1196–1200

MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Extracellular Vesicles
Language	English
Publishing date	2023-05-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.03.033
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Article ; Online: Opportunities and Challenges of Observational Studies and Randomized Controlled Trials for Evaluating the Therapeutic Efficacy of COVID-19 Convalescent Plasma.

Lyman, Gary H / Desai, Aakash / Leyfman, Yan / Kuderer, Nicole M

Cancer investigation

2021 Volume 39, Issue 6-7, Page(s) 449–456

Abstract: Large randomized controlled trials (RCTs) remain the gold standard for evaluating treatment efficacy. However, observational studies, including non-randomized cohort studies, as well as small RCTs have gained increasing attention especially during the ... ...

Abstract	Large randomized controlled trials (RCTs) remain the gold standard for evaluating treatment efficacy. However, observational studies, including non-randomized cohort studies, as well as small RCTs have gained increasing attention especially during the SARS-CoV-2 pandemic where critical evaluation of limited therapeutic options are sought to improve patient care while awaiting results for subsequent RCTs. As the authors have previously discussed, RCTs and observational studies are complementary approaches which often appear synergistic with one another. While not all real-world studies are the same, the results of observational studies are notoriously subject to both known and unknown confounding factors. The utilization of COVID-19 Convalescent Plasma is a timely illustration of evaluating the efficacy and safety of a COVID-19 therapy given the dangerous and often lethal effects of the virus and the limited approved therapeutic options for the disease. While awaiting the results of large RCTS of convalescent plasma, serval observational cohorts and small RCTs have attempted to assess the efficacy and safety of this approach with very mixed results. Among the likely reasons for this failure to provide a definitive answer concerning the value of convalescent plasma are the many limitations inherent to addressing treatment efficacy in non-randomized studies. While such studies are often able to capture information on large numbers of individuals rapidly, it is important to understand that although larger numbers may enhance the precision of estimates provided, larger numbers, in and of themselves, do not increase the accuracy of estimates due to patient selection and other biases. At the same time, both observational studies and small RCTS are at risk for publication bias due to investigator, reviewer and editorial bias toward positive studies. In this commentary we discuss the advantages and limitations of these methodologic approaches when addressing urgently needed evidence on the effectiveness and safety of therapies in a crisis such as the COVID-19 pandemic.
MeSH term(s)	COVID-19/therapy ; Health Services Accessibility ; Humans ; Immunization, Passive/methods ; Observational Studies as Topic ; Publication Bias ; Randomized Controlled Trials as Topic ; Treatment Outcome
Language	English
Publishing date	2021-07-05
Publishing country	England
Document type	Journal Article
ZDB-ID	604942-4
ISSN	1532-4192 ; 0735-7907
ISSN (online)	1532-4192
ISSN	0735-7907
DOI	10.1080/07357907.2021.1942127
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Article ; Online: Immunotherapy in Sarcoma: Where Do Things Stand?

Moreno Tellez, Cristiam / Leyfman, Yan / D'Angelo, Sandra P / Wilky, Breelyn A / Dufresne, Armelle

Surgical oncology clinics of North America

2022 Volume 31, Issue 3, Page(s) 381–397

Abstract: Early experiences with modern immunotherapy have been disappointing in trials of unselected sarcoma subtypes. However, remarkable efficacy has been observed with immune checkpoint inhibitors (ICIs) in a subset of patients, with the most promising ... ...

Abstract	Early experiences with modern immunotherapy have been disappointing in trials of unselected sarcoma subtypes. However, remarkable efficacy has been observed with immune checkpoint inhibitors (ICIs) in a subset of patients, with the most promising outcomes to date in alveolar soft part sarcoma, cutaneous angiosarcoma, undifferentiated pleomorphic sarcoma (UPS), and dedifferentiated liposarcoma (dLPS). Adoptive cellular therapies targeting cancer testis antigens have shown promising activity, but only synovial sarcoma (SS) and myxoid/round cell liposarcomas reliably express these targets. The majority of sarcomas are immunologically "cold" with sparse immune infiltration, which may explain the poor response to immunotherapy. Current immunotherapy trials for sarcomas explore combination therapies with checkpoint inhibitors to overcome immune evasion and novel targets in adoptive cellular therapies. The role of tertiary lymphoid structures, PD-L1 expression, tumor mutational burden, microsatellite instability, and tumor lymphocytes as biomarkers for response are areas of active investigation. In this review, we highlight prior and ongoing clinical efforts to improve outcomes with immunotherapy and discuss the current state of understanding for biomarkers to select patients most likely to benefit from this approach.
MeSH term(s)	Adult ; Biomarkers, Tumor ; Humans ; Immunotherapy ; Liposarcoma/pathology ; Male ; Sarcoma/pathology ; Soft Tissue Neoplasms
Chemical Substances	Biomarkers, Tumor
Language	English
Publishing date	2022-05-31
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1196919-2
ISSN	1558-5042 ; 1055-3207
ISSN (online)	1558-5042
ISSN	1055-3207
DOI	10.1016/j.soc.2022.03.004
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Article ; Online: Professional Challenges for United States Hematology/Oncology Trainees during COVID-19.

Banerjee, Rahul / Kareff, Samuel A / Leyfman, Yan / Dhawan, Natasha / Hammons, Lindsay R / Desai, Aakash / Tsang, Mazie / Velazquez, Ana I / Nizam, Amanda

Cancer investigation

2023 Volume 41, Issue 6, Page(s) 539–547

Abstract: COVID-19 has been devastating for patients with cancer. In this commentary, we chronicle the pandemic's downstream impacts on United States hematology/oncology trainees in terms of professional development and career advancement. These include loss of ... ...

Abstract	COVID-19 has been devastating for patients with cancer. In this commentary, we chronicle the pandemic's downstream impacts on United States hematology/oncology trainees in terms of professional development and career advancement. These include loss of access to clinical electives and protocol workshops, delays in research approval and execution, mentor shortages due to academic burnout, and obstacles with career transitions (most notably the post-fellowship job search). While certain silver linings from the pandemic have undoubtedly emerged, continued progress against COVID-19 will be essential to fully overcome the professional challenges it has created for the future hematology/oncology workforce.
MeSH term(s)	Humans ; United States/epidemiology ; COVID-19/epidemiology ; Medical Oncology ; Fellowships and Scholarships ; Hematology ; Pandemics
Language	English
Publishing date	2023-04-11
Publishing country	England
Document type	Journal Article
ZDB-ID	604942-4
ISSN	1532-4192 ; 0735-7907
ISSN (online)	1532-4192
ISSN	0735-7907
DOI	10.1080/07357907.2023.2199216
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Article: The Evolving Landscape: Exploring the Future of Myelodysplastic Syndrome Treatment with Dr. Rami Komrokji.

Jackewicz, Sean Henry / Coloma, Helena S / Cortiana, Viviana / Joshi, Muskan / Menon, Gayathri P / Balasubramanian, Maduri / Park, Chandler H / Leyfman, Yan

Cancers

2023 Volume 15, Issue 21

Abstract: This perspective delves into the evolving landscape of Myelodysplastic Syndrome (MDS) treatment. MDS presents a significant clinical challenge, often progressing to acute myeloid leukemia. For low-risk MDS, the emphasis is on personalized care through ... ...

Abstract	This perspective delves into the evolving landscape of Myelodysplastic Syndrome (MDS) treatment. MDS presents a significant clinical challenge, often progressing to acute myeloid leukemia. For low-risk MDS, the emphasis is on personalized care through comprehensive risk assessment, clinical monitoring, and tailored interventions, including promising agents like erythropoiesis-stimulating agents, lenalidomide, and luspatercept, with the anticipation of an expanding therapeutic arsenal and early intervention for improved outcomes. In contrast, high-risk MDS treatment is evolving towards upfront doublet or triplet therapies with a focus on minimal residual disease (MRD) monitoring. A holistic approach integrates various modalities, including stem cell transplant and post-transplant maintenance, all guided by individual patient circumstances. Risk-adapted strategies are crucial for enhancing patient outcomes. Precision medicine for MDS treatment is budding, largely driven by Next Generation Sequencing (NGS). NGS aids in early diagnosis, prognostication, and the targeting of specific mutations, with molecular data increasingly informing treatment responses and allowing for tailored interventions. Clinical trials within homogeneous patient groups with similar molecular profiles are becoming more common, enhancing treatment precision. In conclusion, the future of MDS treatment is moving towards personalized medicine, leveraging advanced technologies like NGS and molecular insights to improve outcomes in the realm of hematological malignancies.
Language	English
Publishing date	2023-10-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15215170
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Article ; Online: Cancer and COVID-19: unravelling the immunological interplay with a review of promising therapies against severe SARS-CoV-2 for cancer patients.

Leyfman, Yan / Emmanuel, Nancy / Menon, Gayathri P / Joshi, Muskan / Wilkerson, William B / Cappelli, Jared / Erick, Timothy K / Park, Chandler H / Sharma, Pushpa

Journal of hematology & oncology

2023 Volume 16, Issue 1, Page(s) 39

Abstract: Cancer patients, due to their immunocompromised status, are at an increased risk for severe SARS-CoV-2 infection. Since severe SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation while stimulating hypoxia, and malignancy ... ...

Abstract	Cancer patients, due to their immunocompromised status, are at an increased risk for severe SARS-CoV-2 infection. Since severe SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation while stimulating hypoxia, and malignancy promotes hypoxia-induced cellular metabolic alterations leading to cell death, we propose a mechanistic interplay between both conditions that results in an upregulation of IL-6 secretion resulting in enhanced cytokine production and systemic injury. Hypoxia mediated by both conditions results in cell necrosis, dysregulation of oxidative phosphorylation, and mitochondrial dysfunction. This produces free radicals and cytokines that result in systemic inflammatory injury. Hypoxia also catalyzes the breakdown of COX-1 and 2 resulting in bronchoconstriction and pulmonary edema, which further exacerbates tissue hypoxia. Given this disease model, therapeutic options are currently being studied against severe SARS-COV-2. In this study, we review several promising therapies against severe disease supported by clinical trial evidence-including Allocetra, monoclonal antibodies (Tixagevimab-Cilgavimab), peginterferon lambda, Baricitinib, Remdesivir, Sarilumab, Tocilizumab, Anakinra, Bevacizumab, exosomes, and mesenchymal stem cells. Due to the virus's rapid adaptive evolution and diverse symptomatic manifestation, the use of combination therapies offers a promising approach to decrease systemic injury. By investing in such targeted interventions, cases of severe SARS-CoV-2 should decrease along with its associated long-term sequelae and thereby allow cancer patients to resume their treatments.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Interleukin-6 ; Neoplasms/complications ; Neoplasms/therapy ; Hypoxia
Chemical Substances	Interleukin-6
Language	English
Publishing date	2023-04-13
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2429631-4
ISSN	1756-8722 ; 1756-8722
ISSN (online)	1756-8722
ISSN	1756-8722
DOI	10.1186/s13045-023-01432-6
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