Genetics of Pancreatic Neuroendocrine Tumors
Pancreatic neuroendocrine tumors (pNETs) represent a relatively rare disease; however, the incidence has been increasing during the last 2 decades. Next generation sequencing has greatly increased our understanding of driver mutations in pNETs. Sporadic pNETs have consistently presented with mutations in MEN1, DAXX/ATRX, and genes related to the mammalian target of rapamycin pathway. Inherited pNETs have traditionally been associated with multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome, neurofibromatosis type 1, and tuberous sclerosis complex. The current review expands on the existing knowledge and the rel...
Source: Hematology/Oncology Clinics of North America - September 22, 2022 Category: Cancer & Oncology Authors: Chirayu Mohindroo, Florencia McAllister, Ana De Jesus-Acosta Source Type: research

Cytotoxic Chemotherapy in Advanced Pancreatic Cancer
This article examines specific components of approved first- and second-line therapies for advanced pancreatic cancer treatment and their effectiveness and concludes with a brief exploration of future directions for targeted therapies. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - September 22, 2022 Category: Cancer & Oncology Authors: Muneeb Rehman, Aakib Khaled, Marcus Noel Source Type: research

PARPis and Other Novel, Targeted Therapeutics in Pancreatic Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a mere ∼10% of patients in the United States surviving 5 years from the time of diagnosis. Until recently, the treatment for advanced PDAC differed little based on patient or tumor characteristics. However, recent breakthroughs have identified subgroups of patients who benefit from novel, biomarker-drive n therapies. We review the data and role for PARP inhibitors and for other biomarker-directed therapies, including for patients with NTRK fusions, NRG1 fusions, mismatch repair deficiency, and KRAS p.G12C mutations. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - September 22, 2022 Category: Cancer & Oncology Authors: William J. Chapin, Kim A. Reiss Source Type: research

Palliative and Supportive Care for Individuals with Pancreatic Adenocarcinoma
Individuals with pancreatic adenocarcinoma experience a complex constellation of palliative and supportive care needs. Notably, when caring for patients with pancreatic adenocarcinoma, clinicians must carefully assess and address these individuals ’ palliative and supportive care needs, as these can have important implications related to their treatment experience and care outcomes. Importantly, prior research has consistently demonstrated the benefits of palliative and supportive care interventions for patients with cancer to help address symptom burden, illness understanding, coping mechanisms, and informed decision ma...
Source: Hematology/Oncology Clinics of North America - September 22, 2022 Category: Cancer & Oncology Authors: Ryan D. Nipp Source Type: research

Current Status and Future Directions of Gene-Based Therapy for Pediatric Blood Diseases
Tremendous advances in the clinical application of gene therapy in hematologic disease have transformed the field, particularly over the past 5 years. This explosion of novel approaches has had an important role in the treatment of inherited conditions and other childhood diseases —particularly in areas where current standard-of-care approaches are insufficient. Impressively, the very first approved gene-based therapy in the United States was in the treatment of children and young adults with relapsed/refractory leukemia—illustrating the potential of gene therapy and how it may change our current and future treatment p...
Source: Hematology/Oncology Clinics of North America - July 15, 2022 Category: Cancer & Oncology Authors: Nirali N. Shah, Sung-Yun Pai Tags: Preface Source Type: research

Gene-Based Therapies for Pediatric Blood Diseases
HEMATOLOGY/ONCOLOGY CLINICS OF NORTH AMERICA (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - July 15, 2022 Category: Cancer & Oncology Authors: Nirali N. Shah, Sung-Yun Pai Source Type: research

Copyright
ELSEVIER (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - July 15, 2022 Category: Cancer & Oncology Source Type: research

Contributors
GEORGE P. CANELLOS, MD (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - July 15, 2022 Category: Cancer & Oncology Source Type: research

Contents
Nirali N. Shah and Sung-Yun Pai (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - July 15, 2022 Category: Cancer & Oncology Source Type: research

Forthcoming Issues
Pancreatic Cancer (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - July 15, 2022 Category: Cancer & Oncology Source Type: research

Chimeric Antigen Receptor T-cell Therapy
Chimeric antigen receptor T-cell (CART) therapy has transformed the treatment paradigm for pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), with complete remission rates in key pivotal CD19-CART trials ranging from 65% to 90%. Alongside this new therapy, new toxicity profiles and treatment limitations have emerged, necessitating toxicity consensus grading systems, cooperative group trials, and novel management approaches. This review highlights the results of key clinical trials of CART for pediatric hematologic malignancies, discusses the most common toxicities seen to date, and elu...
Source: Hematology/Oncology Clinics of North America - June 29, 2022 Category: Cancer & Oncology Authors: Aimee C. Talleur, Regina Myers, Colleen Annesley, Haneen Shalabi Source Type: research

Genes as Medicine
The field of gene therapy has experienced tremendous growth in the last decade ranging from improvements in the design of viral vectors for gene addition of therapeutic gene cassettes to the discovery of site-specific nucleases targeting transgenes to desired locations in the genome. Such advancements have not only enabled the development of disease models but also created opportunities for the development of tailored therapeutic approaches. There are 3 main methods of gene modification that can be used for the prevention or treatment of disease. This includes viral vector-mediated gene therapy to supply or bypass a missin...
Source: Hematology/Oncology Clinics of North America - June 28, 2022 Category: Cancer & Oncology Authors: Joseph D. Long, Edward C. Trope, Jennifer Yang, Kristen Rector, Caroline Y. Kuo Source Type: research

Adeno-Associated Virus Vector Design –Moving the Adeno-Associated Virus to a Bioengineered Therapeutic Nanoparticle
Although the number of market-approved gene therapies is still low, this new class of therapeutics has become an integral part of modern medicine. The success and safety of gene therapy depend on the vectors used to deliver the therapeutic material. Adeno-associated virus (AAV) vectors have emerged as the most frequently used delivery system for in  vivo gene therapy. This success was achieved with first-generation vectors, using capsids derived from natural AAV serotypes. Their broad tropism, the high seroprevalence for many of the AAV serotypes in the human population, and the high vector doses needed to transduce a suf...
Source: Hematology/Oncology Clinics of North America - June 28, 2022 Category: Cancer & Oncology Authors: Nico J äschke, Hildegard Büning Source Type: research

Regulatory Aspects of Gene Therapy
This article highlights the life cycle of product development through approval and many of the available resources and programs to support product development. (Source: Hematology/Oncology Clinics of North America)
Source: Hematology/Oncology Clinics of North America - June 27, 2022 Category: Cancer & Oncology Authors: Najat Bouchkouj, Megha Kaushal, Poornima Sharma, Kristin Baird Source Type: research

Genome-Edited T Cell Therapies
Chimeric antigen receptor (CAR) T-cells are widely being investigated against malignancies, and allogeneic ‘universal donor’ CAR-T cells offer the possibility of widened access to pre-manufactured, off-the-shelf therapies. Different genome-editing platforms have been used to address human leukocyte antigen (HLA) barriers to generate universal CAR-T cell therapy and early applications have been report ed in children and adults against B cell malignancies. Recently developed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based systems and related technologies offer the prospect of enhanced cellular im...
Source: Hematology/Oncology Clinics of North America - June 27, 2022 Category: Cancer & Oncology Authors: Giorgio Ottaviano, Waseem Qasim Source Type: research