Cell surface GRP78-directed CAR-T cells are effective at treating human pancreatic cancer in preclinical models

Review Oncology

Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours

Christian L. Flugel et al.

Summary: CAR T cells targeting solid tumour antigens carry a higher risk of on-target, off-tumour toxicity (OTOT), and this article summarizes the available data on OTOT and describes novel CAR T cell designs to overcome such toxicities.

NATURE REVIEWS CLINICAL ONCOLOGY (2023)

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Review Oncology

Current advances and challenges in CAR T-Cell therapy for solid tumors: tumor-associated antigens and the tumor microenvironment

Ting Yan et al.

Summary: The past decade has seen significant progress in immune therapy, specifically in chimeric antigen receptor (CAR) T-cell therapy for cancer treatment. This emerging technique has shown promising advantages in killing cancer cells, achieving high remission rates, rapid tumor eradication, and long-lasting tumor immunity. However, challenges remain in CAR T-cell therapy for solid tumors due to target diversity, tumor heterogeneity, and complex microenvironment.

EXPERIMENTAL HEMATOLOGY & ONCOLOGY (2023)

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Review Oncology

Immunonutrition and prehabilitation in pancreatic cancer surgery: A new concept in the era of ERAS? and neoadjuvant treatment

Raffaele De Luca et al.

Summary: Pancreatic cancer (PC) is a highly aggressive disease with poor prognosis. Neoadjuvant treatments are recommended for borderline resectable and upfront resectable PC. Malnutrition and nutritional imbalance are common in PC, and can negatively impact postoperative and oncological outcomes. Implementing actions and programs to improve nutritional interventions and optimize quality of life for PC patients is important. Current studies and guidelines support the use of medical nutrition to prevent infections and decrease hospital stay. Medical nutrition should be considered proactively to prevent severe malnutrition and its consequences on disease outcomes in PC patients.

EJSO (2023)

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Review Medicine, Research & Experimental

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments

Gunjan Dagar et al.

Summary: Traditional cancer treatments use nonspecific drugs and monoclonal antibodies, while CAR-T cell therapy leverages the immune system's T-cells to recognize and attack tumor cells. Despite success in blood cancers, CAR-T technology faces challenges in solid tumors such as lack of reliable tumor-associated antigens and immunosuppressive tumor environments. To overcome these challenges, current research aims to identify reliable tumor-associated antigens and develop cost-effective, tumor microenvironment-specific CAR-T cells.

JOURNAL OF TRANSLATIONAL MEDICINE (2023)

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Review Chemistry, Multidisciplinary

Nanomedicines enhance minimally invasive therapy of pancreatic cancer

Peipei Yang et al.

Summary: Pancreatic carcinoma (PCa) is a highly lethal malignant tumor with limited treatment options. Nanoparticles have been introduced as a medium or carrier to focus energy at the tumor site and minimize side effects. The combination of nanomedicine and minimally invasive techniques provides a new opportunity for the treatment of PCa.

NANO TODAY (2023)

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Review Gastroenterology & Hepatology

Nutrition support in pancreatic cancer: An expert statement on practical implementation of French guidelines

Julien Taieb et al.

Summary: The 2021 ESPEN guidelines are widely used for nutrition support in cancer patients, but there is a lack of specialized guidelines for different cancer types. The TNCD guidelines developed by French medical and surgical societies provide specific guidelines for patients with digestive cancers and were recently updated in 2022. This review discusses the recommendations of these guidelines for pancreatic cancer management.

CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY (2023)

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Article Oncology

Cancer statistics, 2022

Rebecca L. Siegel et al.

Summary: Each year, the American Cancer Society compiles data on cancer occurrence and outcomes in the United States. The latest data shows that breast and prostate cancer progress has stagnated, while lung cancer has shown improvements in survival rates. Lung cancer incidence for advanced disease has declined while localized-stage rates have increased, resulting in higher survival rates. Mortality patterns align with incidence trends, with lung cancer deaths declining rapidly, breast cancer deaths slowing, and prostate cancer deaths stabilizing.

CA-A CANCER JOURNAL FOR CLINICIANS (2022)

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Article Oncology

Linking cell-surface GRP78 to cancer: From basic research to clinical value of GRP78 antibodies

Isabelle Hernandez et al.

Summary: csGRP78 is a protein that appears on the surface of cancer cells, playing a key role in cancer development by influencing intracellular signaling pathways, and thus associated with the maintenance and progression of the disease.

CANCER LETTERS (2022)

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Article Multidisciplinary Sciences

CAR T cells redirected to cell surface GRP78 display robust anti-acute myeloid leukemia activity and do not target hematopoietic progenitor cells

Nikhil Hebbar et al.

Summary: The study demonstrates that targeting cell surface GRP78-positive AML with CAR T cells is feasible and shows significant anti-AML activity in preclinical models. The findings suggest that GRP78 could be a suitable target for CAR-T therapy in patients with acute myeloid leukemia.

NATURE COMMUNICATIONS (2022)

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Review Oncology

The next wave of cellular immunotherapies in pancreatic cancer

Dannel Yeo et al.

Summary: Pancreatic cancer is a highly aggressive disease that is expected to become the second leading cause of cancer-related death worldwide. Current treatments for pancreatic cancer are limited, and cellular immunotherapy, particularly CAR T cell therapy, has shown limited efficacy. This review provides an overview of ongoing clinical studies and strategies to improve CAR T cell efficacy in pancreatic cancer.

MOLECULAR THERAPY-ONCOLYTICS (2022)

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Article Cell Biology

Chimeric Antigen Receptor T Cells Targeting Cell Surface GRP78 to Eradicate Acute Myeloid Leukemia

Wei Yu et al.

Summary: This study developed a novel CAR structure targeting GRP78, a cell surface protein, to achieve anti-tumor effects against AML cells without harming normal hematopoietic stem cells. These findings provide a promising approach for the therapy of AML.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Review Pharmacology & Pharmacy

Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects

Javad Masoumi et al.

Summary: CSCs are cells with self-renewal ability that initiate tumors and are potential targets for novel anticancer therapeutic agents. CAR-T cells, engineered T cells expressing an artificial receptor specific for TAAs, have shown higher efficiency in cancer treatment by accurately targeting and killing cancer cells.

ACTA PHARMACEUTICA SINICA B (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Oncology

Integrative Genomic Analysis of Gemcitabine Resistance in Pancreatic Cancer by Patient-derived Xenograft Models

Gang Yang et al.

Summary: This study identified key genes and microRNA associated with gemcitabine resistance in pancreatic cancer cells, and potential biomarker miR-135a-5p for predicting drug response. Moreover, changes in PI3K-Akt, p53, and hypoxia-inducible factor-1 pathways were observed in multiple patients before and after treatment, suggesting potential target pathways for reducing acquired resistance.

CLINICAL CANCER RESEARCH (2021)

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Article Biochemistry & Molecular Biology

ER residential chaperone GRP78 unconventionally relocalizes to the cell surface via endosomal transport

Richard Van Krieken et al.

Summary: Recent research has revealed that ER chaperones such as GRP78 can escape from the ER and traffic to the cell surface in colon and lung cancer via a non-traditional endosomal transport pathway mediated by Rab GTPases. This unconventional translocation mechanism is driven by membrane fusion between ER-derived vesicles and endosomes, requiring specific SNARE proteins and co-chaperones regulated by ER stress-induced signaling pathways.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

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Review Biochemistry & Molecular Biology

Pancreatic Ductal Adenocarcinoma: The Dawn of the Era of Nuclear Medicine?

Christopher Montemagno et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC), which accounts for 90-95% of all pancreatic tumors, is a highly devastating disease with poor prognosis due to the lack of accurate diagnostic tests and failure of conventional therapies. Recent developments in nuclear medicine have opened up great opportunities for the management of PDAC, with the development of radiotracers and theranostics showing promise in diagnostic and therapeutic applications.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Gastroenterology & Hepatology

Cell death in pancreatic cancer: from pathogenesis to therapy

Xin Chen et al.

Summary: Pancreatic cancer is a devastating gastrointestinal cancer with late diagnosis, limited treatment success and poor prognosis, primarily composed of pancreatic ductal adenocarcinoma (PDAC). The occurrence and progression of PDAC are influenced by various factors, and the exact impact of cell death on PDAC is not yet well described.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Review Oncology

Targeting the Stroma in the Management of Pancreatic Cancer

Penelope Edwards et al.

Summary: Pancreatic cancer is known for its aggressive nature and poor survival, largely due to the unique features of the tumor microenvironment. The stromal components in the TME play a crucial role in the progression and chemoresistance of PC, leading to the development of promising agents targeting these components.

FRONTIERS IN ONCOLOGY (2021)

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Review Chemistry, Medicinal

Hacking Pancreatic Cancer: Present and Future of Personalized Medicine

Alessandro Di Federico et al.

Summary: Pancreatic cancer is a challenging disease with a complex genomic landscape that affects tumor microenvironment, leading to tumor growth and drug resistance. Despite chemotherapy being the mainstay of treatment, personalized medicine has shown promising results with some drugs.

PHARMACEUTICALS (2021)

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Review Oncology