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Review
Pathology
Mara H. Sherman et al.
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a diverse stromal microenvironment that plays a significant role in disease biology and treatment resistance. Recent advancements in imaging, single-cell analytics, and disease modeling have provided insights into the complexity of PDAC tumors. Understanding the functional and spatial dependencies between cancer cells and extracellular matrix components can reveal therapeutic vulnerabilities.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2023)
Review
Oncology
Christoph Springfeld et al.
Summary: This article discusses the treatment strategies for pancreatic ductal adenocarcinoma (PDAC), including surgical resection and systemic chemotherapy. Neoadjuvant chemotherapy may improve the survival outcomes of patients with borderline-resectable PDAC. For patients with unresectable PDAC, undergoing chemotherapy may lead to surgical resection and improved survival outcomes.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Review
Oncology
Kilian B. Kennel et al.
Summary: Tumor-associated inflammation (TAI) is a common feature in cancers, and cancer-associated fibroblasts (CAF) play a crucial role in modulating TAI. CAFs exhibit remarkable plasticity and can shift their phenotypes and functions in response to environmental changes. This review explores how CAFs contribute to tumor-promoting inflammation and suppress adaptive immunity, as well as the potential therapeutic strategies targeting CAFs in combination with immunotherapy.
CLINICAL CANCER RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Dakai Yang et al.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Review
Chemistry, Multidisciplinary
Jun-hao Li et al.
Summary: Immunotherapy, specifically immune checkpoint blockade therapy targeting the PD-1/PD-L1 axis, has revolutionized cancer treatment. However, current therapy faces challenges including low tumor specificity, severe cytotoxic effects, and immune resistance. Nanosized drug delivery systems (NDDSs) offer a new avenue for cancer immunotherapy.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Gastroenterology & Hepatology
Laura D. Wood et al.
Summary: This review discusses the pathogenesis, early detection methods, and treatment considerations of pancreatic ductal adenocarcinoma (PDAC). Recent advances in understanding PDAC have led to significant improvements in detection and treatment, but coordinated efforts are needed to maximize clinical impact for patients and overall survival.
Article
Pharmacology & Pharmacy
Jonathan M. Maher et al.
Summary: This study demonstrated that localized pulmonary delivery of an ALK5 inhibitor leads to favorable TGF beta pathway pharmacodynamic inhibition in lung while minimizing key systemic toxicities.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Article
Oncology
Kathleen M. McAndrews et al.
Summary: The study identifies two distinct populations of fibroblasts with opposing roles in the progression and immune landscape of PDAC. Fibroblasts play diverse functions in regulating cancer-associated pathways and accumulation of regulatory T cells, impacting therapeutic efficacy in PDAC treatment. This finding reveals the functional heterogeneity of CAFs in PDAC progression, with significant implications for therapy response.
Article
Chemistry, Multidisciplinary
Bo Hou et al.
Summary: Due to pathophysiological barriers, the immune-excluded tumors (IETs) have limited response to current immune blockade therapy. In this study, a clickable prodrug nanoplatform was proposed to enhance immunotherapy of IETs by improving intratumoral infiltration of cytotoxic T lymphocytes (CTLs). The nanoplatform consisted of acidity-activatable nanoparticles and sequentially activated in the tumor microenvironment to promote the regression of IETs.
Article
Pharmacology & Pharmacy
Jiayi Ye et al.
Summary: A bispecific prodrug nanoparticle was engineered to target multiple immune resistance mechanisms in tumor cells and improve cancer immunotherapy. The nanoparticle combines photodynamic therapy (PDT) to induce immunogenic cell death, providing a novel strategy for blocking immune evasion pathways.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Nanoscience & Nanotechnology
Huijuan Zhang et al.
Summary: A dual-responsive and biodegradable polypeptide nanoparticle has been developed for combinatory chemotherapy and photodynamic therapy of breast cancer. The nanoparticle can be activated by acidic conditions and efficiently deliver drugs to tumor cells, inhibiting tumor growth and metastasis.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Multidisciplinary Sciences
Akshay T. Krishnamurty et al.
Summary: The study reveals the crucial role of TGF beta-dependent LRRC15(+) CAFs in tumor growth, as well as their direct impact on CD8(+) T cell function and responsiveness to checkpoint blockade.
Article
Multidisciplinary Sciences
Hua Su et al.
Summary: This study reveals the opposing effects of intact and cleaved collagen I (Col I) in regulating the bioenergetics, tumor growth, and metastasis of pancreatic ductal adenocarcinoma (PDAC) through the tumor microenvironment. Intact Col I inhibits tumor growth, while cleaved Col I promotes tumor growth. Patients with tumors enriched in intact Col I and low levels of related signaling molecules have a longer median survival. These findings shed light on the complex mechanisms of the tumor microenvironment in PDAC and provide new therapeutic targets.
Article
Chemistry, Multidisciplinary
Jiayi Ye et al.
Summary: The success of immunotherapy, particularly immune checkpoint blockade therapy, has been witnessed in the current era. However, the complex tumor microenvironment and the immune resistance of tumor cells often hinder the effectiveness of immunotherapy. In recent years, scientists have developed bioinspired nanotherapeutics to overcome cancer immune resistance and enhance immunotherapy. These nanotherapeutics can deliver immunotherapeutics specifically to tumor cells by responding to signals in the tumor microenvironment, and they can also inhibit immune checkpoints to relieve adaptive immune resistance. The strategies mentioned in this article provide potential solutions for the clinical therapy of immune-resistant cancer.
ACCOUNTS OF MATERIALS RESEARCH
(2022)
Review
Oncology
Marilyne Labrie et al.
Summary: Normal and cancer cells utilize adaptive responses to survive environmental stresses, and this Review discusses how tumor ecosystems adapt to therapeutic stresses and how these adaptations can be exploited to overcome cancer therapy resistance.
NATURE REVIEWS CANCER
(2022)
Review
Immunology
Mary Philip et al.
Summary: The article discusses the dysfunctional states of CD8(+) T cells in tumors and their impact on response and resistance to immunotherapy. The authors emphasize the heterogeneity of T cell states in tumors and the challenge of predicting which patients will respond to immunotherapeutic interventions.
NATURE REVIEWS IMMUNOLOGY
(2022)
Article
Immunology
Yuying Liu et al.
Summary: IL-2 acts as an environmental cue to induce CD8(+) T cell exhaustion within tumor microenvironments by activating STAT5, inducing tryptophan hydroxylase 1, and subsequently causing T cell dysfunction.
Editorial Material
Gastroenterology & Hepatology
Tejeshwar Jain et al.
Summary: In 2020, significant progress was made in three major areas of pancreatic ductal adenocarcinoma (PDAC) research: risk factors, therapeutic resistance, and tumor recurrence. The pathophysiology of obesity-mediated PDAC initiation was elucidated, novel stromal mechanisms of therapeutic resistance were unveiled, and the genetic evolution of recurrent PDAC under therapeutic pressures was tracked in human samples.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Oncology
Yang Chen et al.
Summary: The stromal desmoplastic reaction in pancreatic ductal adenocarcinoma involves significant accumulation of type I collagen (Col1). Deletion of Col1 specifically in myofibroblasts accelerates PDAC progression by increasing Cxcl5 expression in cancer cells and promoting recruitment of myeloid-derived suppressor cells. Targeting CXCR2 and CCR2 may help restrain accelerated PDAC progression in the absence of stromal Col1.
Review
Biochemistry & Molecular Biology
Xiaoqi Mao et al.
Summary: CAFs, as a crucial component of TME, play significant roles in promoting tumor growth, invasion, and metastasis. The interaction between CAFs and tumor cells, as well as immune cells in TIME, is critical for tumor progression.
Review
Biotechnology & Applied Microbiology
Shawn P. Kubli et al.
Summary: The review discusses the history of immunotherapy and checkpoint blockade, emphasizing key clinical failures. It highlights critical aspects of immune processes within the tumor microenvironment, which may guide the development of new therapeutic strategies in immuno-oncology. Future successful therapeutics are likely to focus on rescuing T cell homing and dysfunction in the tumor microenvironment, as well as reappropriating mononuclear phagocyte function for inflammatory remodeling of the TME. New drugs will need to consider the complex cell networks within tumors and across different cancer types.
NATURE REVIEWS DRUG DISCOVERY
(2021)
Review
Chemistry, Multidisciplinary
Weiqi Wang et al.
Summary: Stimuli-activatable nanomedicines show promise in improving cancer immunotherapy by enhancing treatment efficiency and reducing side effects through tumor-specific accumulation, controllable drug release, and combinational therapy. These nanomedicines can target tumor cells, immune cells, or peripheral immune systems to elicit sustained systemic immune activation and modulate the immunosuppressive tumor microenvironment.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Review
Chemistry, Multidisciplinary
Madiha Saeed et al.
Summary: This article discusses how nanotechnology-based methods can promote anti-tumor immune responses, with a focus on the importance of normalizing the tumor immune microenvironment. By targeting immunosuppressive cells and signaling pathways, nanomedicine has the potential to enhance the impact of cancer immunotherapy.
ADVANCED MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Kazuhiro Koikawa et al.
Summary: Upregulation of Pin1 in PDAC contributes to the desmoplastic and immunosuppressive TME, but targeting Pin1 with available drugs can synergize with immunotherapy and gemcitabine to induce complete elimination of PDAC.
Article
Chemistry, Multidisciplinary
Na Song et al.
Summary: The study demonstrates the oxidation-regulated self assembly of peptides into transformable scaffolds for cascade cancer therapy via in situ ROS generation. The scaffolds with combinatorial therapeutic effect promoted by photo-induced in situ ROS generation and morphological transition due to methionine oxidation enhance tumor accumulation and penetration of therapeutics, leading to effective tumor eradication. The findings provide a new and versatile strategy for ROS-associated disease treatment in the future.
Review
Oncology
Yang Chen et al.
Summary: CAFs, as highly versatile and resilient cells in primary and metastatic tumors, play crucial roles in cancer progression through complex interactions with other cell types in the tumor microenvironment. Their heterogeneity and dynamic interactions are key factors in cancer development.
NATURE REVIEWS CLINICAL ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Fanglong Wu et al.
Summary: CAFs play vital roles in cancer progression and their complex signaling pathways with cancer cells are crucial for understanding the development of cancer.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2021)
Article
Chemistry, Multidisciplinary
Bo Hou et al.
ADVANCED MATERIALS
(2020)
Review
Chemistry, Multidisciplinary
Jing Gao et al.
ACTA PHARMACOLOGICA SINICA
(2020)
Editorial Material
Oncology
Filip Bednar et al.
Article
Medicine, General & Internal
Jonathan D Mizrahi et al.
Review
Chemistry, Multidisciplinary
Bin Yang et al.
Article
Oncology
Ela Elyada et al.
Review
Biotechnology & Applied Microbiology
Xueman Chen et al.
NATURE REVIEWS DRUG DISCOVERY
(2019)
Article
Oncology
Giulia Biffi et al.
Article
Immunology
Christian U. Blank et al.
NATURE REVIEWS IMMUNOLOGY
(2019)
Article
Multidisciplinary Sciences
Julie Stockis et al.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Correction
Oncology
Berna C. Oezdemir et al.
Article
Oncology
Albert Lo et al.
Article
Biochemistry & Molecular Biology
Mara H. Sherman et al.
Article
Multidisciplinary Sciences
Christine Feig et al.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2013)
Article
Oncology
Paolo P. Provenzano et al.
Article
Oncology
Elinborg Ostermann et al.
CLINICAL CANCER RESEARCH
(2008)
