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Nature Reviews. Gastroenterology &... Jun 2022The burgeoning field of intratumoural microbiome research has been driven by advances in next-generation sequencing technologies, with compelling evidence on the role of...
The burgeoning field of intratumoural microbiome research has been driven by advances in next-generation sequencing technologies, with compelling evidence on the role of the microbiota in cancer initiation, progression and patient response to treatment. Here, we discuss new concepts of the tumour-associated microbiota and what is needed to advance the translational impact of these findings in gastrointestinal cancers.
Topics: Humans; Microbiota; Neoplasms
PubMed: 35361914
DOI: 10.1038/s41575-022-00609-7 -
Cell Communication and Signaling : CCS May 2024Cancer's complexity is in part due to the presence of intratumor heterogeneity and the dynamic nature of cancer cell plasticity, which create substantial obstacles in...
Cancer's complexity is in part due to the presence of intratumor heterogeneity and the dynamic nature of cancer cell plasticity, which create substantial obstacles in effective cancer management. Variability within a tumor arises from the existence of diverse populations of cancer cells, impacting the progression, spread, and resistance to treatments. At the core of this variability is the concept of cellular plasticity - the intrinsic ability of cancer cells to alter their molecular and cellular identity in reaction to environmental and genetic changes. This adaptability is a cornerstone of cancer's persistence and progression, making it a formidable target for treatments. Emerging studies have emphasized the critical role of such plasticity in fostering tumor diversity, which in turn influences the course of the disease and the effectiveness of therapeutic strategies. The transformative nature of cancer involves a network of signal transduction pathways, notably those that drive the epithelial-to-mesenchymal transition and metabolic remodeling, shaping the evolutionary path of cancer cells. Despite advancements, our understanding of the precise molecular machinations and signaling networks driving these changes is still evolving, underscoring the necessity for further research. This editorial presents a series entitled "Signaling Cancer Cell Plasticity and Intratumor Heterogeneity" in Cell Communication and Signaling, dedicated to unraveling these complex processes and proposing new avenues for therapeutic intervention.
Topics: Humans; Neoplasms; Cell Plasticity; Signal Transduction; Animals; Epithelial-Mesenchymal Transition
PubMed: 38702718
DOI: 10.1186/s12964-024-01643-5 -
Clinical Advances in Hematology &... Oct 2021The uses of immune checkpoint inhibitors have now been advanced to include the first-line treatment of esophagogastric cancers. Initially approved for the treatment of... (Review)
Review
The uses of immune checkpoint inhibitors have now been advanced to include the first-line treatment of esophagogastric cancers. Initially approved for the treatment of chemotherapy-refractory programmed death ligand 1-positive or microsatellite instability (MSI)-high esophagogastric adenocarcinoma, these agents have been shown in earlier-line trials to have an additive benefit with first-line chemotherapy, and superiority to chemotherapy, in MSI-high cancers. Pembrolizumab and nivolumab have received approval for the second-line treatment of esophageal squamous cancer. The addition of nivolumab to first-line chemotherapy in gastric and gastroesophageal junction (GEJ) adenocarcinoma improved survival, progression-free survival, and response, findings that led to regulatory approval. The addition of pembrolizumab to first-line chemotherapy in esophageal and GEJ adenocarcinoma and squamous cancer also improved all outcomes, which led to the approval of pembrolizumab as part of first-line chemotherapy. The addition of pembrolizumab to first-line chemotherapy in human epidermal growth factor receptor 2-positive esophagogastric adenocarcinoma was also recently approved. In addition, the adjuvant use of nivolumab was recently approved in esophageal and GEJ cancer after chemoradiotherapy and surgery in patients with residual disease found at surgery. This article reviews recent advances in the use of immune checkpoint inhibitor therapy in esophagogastric cancers.
Topics: Adenocarcinoma; Esophageal Neoplasms; Humans; Immunotherapy; Nivolumab; Stomach Neoplasms
PubMed: 34637430
DOI: No ID Found -
Current Treatment Options in Oncology Dec 2023Ovarian carcinosarcoma (OCS), also known as a malignant mixed Müllerian tumour (MMMT), is a rare and aggressive form of cancer that accounts for less than 5% of ovarian... (Review)
Review
Ovarian carcinosarcoma (OCS), also known as a malignant mixed Müllerian tumour (MMMT), is a rare and aggressive form of cancer that accounts for less than 5% of ovarian cancers. It is characterized by high morbidity and mortality rates, with a median overall survival (OS) of less than 2 years. Several factors, including advancing age, nulliparity, reduced lactation rates, decreased use of oral contraceptive pills, genetic mutations in BRCA (breast cancer) genes, and the use of assisted reproductive technology, may increase the risk of OCS. Poor prognostic factors include an advanced stage at diagnosis, older age, lymph node metastasis, suboptimal surgical cytoreduction, the presence of heterologous features on histopathology, and increased expression of vascular endothelial growth factor (VEGF), tumour protein p53, and p53 alongside Wilms tumour 1 (WT1). The main treatment approach for OCS is cytoreductive surgery followed by platinum-based chemotherapy, although immunotherapy is showing promise. Homologous recombination deficiency (HRD) testing may enhance outcomes by enabling personalized immunotherapy and targeted therapies for specific patient groups, thereby reducing unnecessary side effects and healthcare costs. However, there is currently a lack of standardised treatment regimens for OCS patients, with most studies consisting of case reports and a shortage of suitable comparator groups. This article aims to provide clinicians with information on the epidemiology, risk factors, prognostic factors, and latest therapeutic advancements in OCS.
Topics: Female; Humans; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Ovarian Neoplasms; Carcinosarcoma
PubMed: 37938504
DOI: 10.1007/s11864-023-01138-4 -
European Urology Oncology Jun 2023While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor,... (Review)
Review
CONTEXT
While urothelial and renal cell cancers have exhibited modest responses to novel immune checkpoint inhibitors targeting the programmed death ligand 1 and its receptor, response rates in patients with prostate cancer have remained poor. The factors underlying suboptimal outcomes observed in patients treated with novel immunotherapies are still to be resolved.
OBJECTIVE
To review the literature and describe the key adaptive immune physiological events associated with cancer progression and therapeutic response in genitourinary (GU) cancers.
EVIDENCE ACQUISITION
We performed a nonsystematic, collaborative narrative review to highlight recent advancements leading to the current state of knowledge on the critical mediators of antitumor adaptive immunity to GU cancers. Further, we discuss the findings on the pre- and post-treatment immunological events that either are unique to each of the three cancer types or exhibit overlapping clinical associations.
EVIDENCE SYNTHESIS
Aging-associated immune function decline is a major factor underlying poor outcomes observed in patients treated with both conventional and novel immunotherapies. Other cancer immunobiological aspects associated with suboptimal responses in GU cancers include the overall tumor mutational burden, mutations in specific tumor suppressor/DNA damage repair genes (KDM6A, PTEN, STAG2, TP53, ATM, and BRCA2), and abundance of multiple functional states of adaptive immune cells and their spatiotemporal localization within the tumor immune microenvironment. Understanding these mechanisms may potentially lead to the development of prognostic and predictive biomarkers such as immune cell infiltration profiles and tertiary lymphoid structures (TLSs) that associate with variable clinical outcomes depending on the nature of the novel immunotherapeutic approach. Implementation of newer immune-monitoring technologies and improved preclinical modeling systems will augment our understanding of the host and tumor intrinsic factors contributing to the variability of responses to immunotherapies.
CONCLUSIONS
Despite the tremendous progress made in the understanding of dynamic and static adaptive immune elements within the tumor immune landscape, several knowledge gaps remain. A comprehensive knowledge thus gained will lead to precision immunotherapy, improved drug sequencing, and a therapeutic response.
PATIENT SUMMARY
We performed a collaborative review by a diverse group of experts in the field to examine our understanding of the events and crosstalk between cancer cells and the patient's immune system that are associated with responses to novel immunotherapies. An evolving understanding of tumor-intrinsic and host-related immune alterations, both before and after therapy, will aid in the discovery of promising markers of responses to immunotherapy as well as the development of unique therapeutic approaches for the management of genitourinary cancers.
Topics: Male; Humans; Urogenital Neoplasms; Prognosis; Prostatic Neoplasms; Adaptive Immunity; Biomarkers, Tumor; Tumor Microenvironment
PubMed: 37069029
DOI: 10.1016/j.euo.2023.03.002 -
Cells Jul 2021Metastasis accounts for the highest mortality rates in solid tumor cancer patients. However, research and development have neglected this most lethal characteristic and,...
Metastasis accounts for the highest mortality rates in solid tumor cancer patients. However, research and development have neglected this most lethal characteristic and, instead, have concentrated on the hallmarks of cancer that make tumor cells highly proliferative and distinctive from nonmalignant cells. The concentration on invasion and metastasis can be one of the most meaningful advancements in cancer investigation. Importantly, metastasis-free survival (MFS) was recently approved by the Food and Drug Administration (FDA) as a novel primary endpoint in clinical trials and has been used to evaluate the prognosis of patients with nonmetastatic castration-resistant prostate cancer and soft tissue sarcoma. This new definition enables to shift the focus of research and development in cancer therapeutics toward metastasis and to change the emphasis from using tumor shrinkage as a benchmark for indicating the efficacy of treatment to using MFS as a more representative endpoint for antimetastatic drugs. This perspective outlines the possibility to use this novel endpoint in other solid cancers, and examples of large clinical trials are given in which MFS is defined as an endpoint and/or in which antimetastatic strategies are being examined. These advances now open the door for the rapid development of antimetastatic therapies, which could be used in combination with standard cytotoxic cancer therapies. With pioneer research on metastasis prevention on the rise and the underlying biomechanisms of tumor cell motility and invasion explored further than ever before, we believe an intensified focus on antimetastatic properties will shape this era of cancer translational research.
Topics: Animals; Antineoplastic Agents; Cell Movement; Clinical Trials as Topic; Endpoint Determination; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Progression-Free Survival; Research Design; Translational Research, Biomedical
PubMed: 34440616
DOI: 10.3390/cells10081845 -
Trends in Pharmacological Sciences May 2023Autophagy is a cellular homeostasis mechanism that fuels the proliferation and survival of advanced cancers by degrading and recycling organelles and proteins.... (Review)
Review
Autophagy is a cellular homeostasis mechanism that fuels the proliferation and survival of advanced cancers by degrading and recycling organelles and proteins. Preclinical studies have identified that within an established tumor, tumor cell autophagy and host cell autophagy conspire to support tumor growth. A growing body of evidence suggests that autophagy inhibition can augment the efficacy of chemotherapy, targeted therapy, or immunotherapy to enhance tumor shrinkage. First-generation autophagy inhibition trials in cancer using the lysosomal inhibitor hydroxychloroquine (HCQ) have produced mixed results but have guided the way for the development of more potent and specific autophagy inhibitors in clinical trials. In this review, we will discuss the role of autophagy in cancer, newly discovered molecular mechanisms of the autophagy pathway, the effects of autophagy modulation in cancer and host cells, and novel autophagy inhibitors that are entering clinical trials.
Topics: Humans; Neoplasms; Hydroxychloroquine; Autophagy
PubMed: 36931971
DOI: 10.1016/j.tips.2023.02.003 -
Trends in Cancer Apr 2023Despite advances in understanding tumor biology, malignant gliomas remain incurable. While immunotherapy has improved outcomes in other cancer types, comparable efficacy... (Review)
Review
Despite advances in understanding tumor biology, malignant gliomas remain incurable. While immunotherapy has improved outcomes in other cancer types, comparable efficacy has not yet been demonstrated for primary cancers of the central nervous system (CNS). T cell exhaustion, defined as a progressive decrease in effector function, sustained expression of inhibitory receptors, metabolic dysfunction, and distinct epigenetic and transcriptional alterations, contributes to the failure of immunotherapy in the CNS. Herein, we describe recent advances in understanding the drivers of T cell exhaustion in the glioma microenvironment. We discuss the extrinsic and intrinsic factors that contribute to exhaustion and highlight potential avenues for reversing this phenotype. Our ability to directly target specific immunosuppressive drivers in brain cancers would be a major advance in immunotherapy.
Topics: Humans; T-Cell Exhaustion; Glioma; Brain Neoplasms; Central Nervous System; Immunotherapy; Tumor Microenvironment
PubMed: 36681605
DOI: 10.1016/j.trecan.2022.12.008 -
Current Opinion in Obstetrics &... Feb 2020This review will provide an update on the most recent clinical developments in immuno-oncology in advanced gynecologic cancers and will also highlight ongoing studies in... (Review)
Review
PURPOSE OF REVIEW
This review will provide an update on the most recent clinical developments in immuno-oncology in advanced gynecologic cancers and will also highlight ongoing studies in this field.
RECENT FINDINGS
Although immune checkpoint blockade (ICB) therapy is rapidly altering the treatment landscape in a myriad of solid tumors, the efficacy of ICB therapy with antibodies directed against CTLA-4, PD-1, and PD-L1 in advanced gynecologic cancers has been limited. The exception has been the PD-1 inhibitor pembrolizumab in microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR) advanced endometrial cancers, highlighted by the recent conditional approval of pembrolizumab in recurrent/metastatic PD-L1-positive cervical cancers and the accelerated approval of pembrolizumab and lenvatinib in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) advanced endometrial cancer. The discovery of novel, rational ICB combinatorial approaches in advanced gynecologic cancers is highly warranted.
SUMMARY
Recent advances in the genomic characterization of gynecologic malignancies have informed clinical trial design. However, improved molecular and immunophenotypic biomarkers to more accurately identify patients who will most benefit from immunotherapeutic approaches are urgently needed. This is especially critical as we attempt to integrate immune-oncology agents, chemotherapy, targeted therapy, and radiation therapy in the management of gynecologic cancers.
Topics: Endometrial Neoplasms; Female; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms
PubMed: 31833942
DOI: 10.1097/GCO.0000000000000603 -
Acta Pharmacologica Sinica Jul 2020Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms... (Review)
Review
Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms of enhancing therapeutic benefits and decreasing the side effects of cancer immunotherapy. Advanced nanobiomaterials, including liposomes, polymers, and silica, play a vital role in the codelivery of drugs and immunomodulators. These nanobiomaterial-based delivery systems could effectively promote antitumor immune responses and simultaneously reduce toxic adverse effects. Furthermore, nanobiomaterials may also combine with each other or with traditional drugs via different mechanisms, thus giving rise to more accurate and efficient tumor treatment. Here, an overview of the latest advancement in these nanobiomaterials used for cancer immunotherapy is given, describing outstanding systems, including lipid-based nanoparticles, polymer-based scaffolds or micelles, inorganic nanosystems, and others.
Topics: Biocompatible Materials; Humans; Immunotherapy; Nanoparticles; Neoplasms
PubMed: 32123302
DOI: 10.1038/s41401-020-0372-z