The impact of targeted therapies in glioma has been modest. All the therapies that have demonstrated a significant survival benefit for gliomas in Phase III trials, including radiation, chemotherapy ...(temozolomide and PCV procarbazine, lomustine, vincristine), and tumor-treating fields, are based on nonspecific targeting of proliferating cells. Recent advances in the molecular understanding of gliomas suggest some potential reasons for the failure of more targeted therapies in gliomas. Specifically, the histologic-based glioma classification is composed of multiple different molecular subtypes with distinct biology, natural history, and prognosis. As a result of these insights, the diagnosis and classification of gliomas have recently been updated by the World Health Organization. However, these changes and other novel observations regarding glioma biomarkers and subtypes highlight several clinical challenges. First, the field is faced with the difficulty of reinterpreting the results of prior studies and retrospective data using the new classifications to clarify prognostic assessments and treatment recommendations for patients. Second, the new classifications and insights require rethinking the design and stratification of future clinical trials. Last, these observations provide the essential framework for the development and testing of new specific targeted therapies for particular glioma subtypes. This review aims to summarize the current literature regarding glioma subclassifications and their clinical relevance in this evolving field.
Cardiotoxic effects of chemotherapy and targeted drugs are ubiquitous and challenging in the field of oncology therapeutics. The broad spectrum of toxicities ranging from ischemic, hypertensive, ...cardiomyopathic, and arrhythmic complications can present as a significant challenge for clinicians treating cancer patients. If early diagnosis and intervention of cardiotoxic complications is missed, this can lead to delay or abrogation of planned treatment, which can potentially culminate to significant morbidity due to not only the cardiotoxic complications but also the progression of cancer. Hence, full knowledge of cardiovascular complications of chemotherapeutic agents, essential diagnostics tests to order, and appropriate management is paramount to oncologist, oncology pharmacists, and scientific clinical investigators. The aforementioned is particularly true in the current oncology era of plenteous early clinical trials studying several pathway/molecular-targeting agents with an increased cardiotoxic potential and the rapid expedited approval of those drugs by the FDA. Herein, we present a review discussing cardiotoxic effects of drugs and guidelines for management of the toxicities to assist the medical field in general managing patients with cancer.
Lung cancer in China: current and prospect Wu, Fengying; Wang, Lei; Zhou, Caicun
Current opinion in oncology,
2021-January, 2021-Jan, 2021-01-00, 20210101, Letnik:
33, Številka:
1
Journal Article
PURPOSE OF REVIEWTo describe the current status of lung cancer in China, including incidence, prevention, molecular testing and treatment.
RECENT FINDINGSLung cancer presents a major public health ...issue and an enormous burden on society in China, because of its increasing incidence and high mortality. Several distinct gene profiles were associated with lung cancer in Chinahigh EGFR mutation rate, low KRAS mutation rate and more comorbidity of HBV infection. Thus, local Chinese Society of Clinical Oncology Guidelines with more consideration of drug accessibility, regional development differences were highly recommended for clinical practice. For treatment, targeted therapy has achieved fruitful progress. Immunotherapy in China was a little bit lag behind previously and now there is a surge of immunotherapeutic drugs under investigation. For future, more preventive strategies and more trials considering chrematistics of Chinese lung cancer are needed.
SUMMARYThere are achievements and shortcomings for lung cancer prevention and treatment in China. More work considering distinct characteristic of lung caner in China are needed.
Esophageal cancer is characterized by early and frequent metastasis. Surgery is the primary treatment for early-stage disease, whereas patients with patients with locally advanced disease receive ...perioperative chemotherapy or chemoradiotherapy. Squamous cancers can be treated with primary chemoradiotherapy without surgery, depending on their response to therapy and patient tolerance for subsequent surgery. Chemotherapy with a fluorinated pyrimidine and a platinum agent, followed by later treatment with taxanes and irinotecan, provides some benefit. Agents that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2), or vascular endothelial growth factor, including trastuzumab, ramucirumab, and apatinib, increase response and survival times. Esophageal adenocarcinomas have mutations in tumor protein p53 and mutations that activate receptor-associated tyrosine kinase, vascular endothelial growth factor, and cell cycle pathways, whereas esophageal squamous tumors have a distinct set of mutations. Esophageal cancers develop systems to evade anti-tumor immune responses, but studies are needed to determine how immune checkpoint modification contributes to esophageal tumor development.
The role of NCAPH in cancer treatment Liu, Caiyan; Han, Xiao; Zhang, Siqi ...
Cellular signalling,
September 2024, 2024-09-00, 20240901, Letnik:
121
Journal Article
Recenzirano
Many solid tumors frequently overexpress Non-SMC Condensin I Complex Subunit H (NCAPH), and new studies suggest that NCAPH may be a target gene for clinical cancer therapy. Numerous investigations ...have shown that a variety of transcription factors, including as MYBL2, FOXP3, GATA3, and OTC1, can stimulate the transcription of NCAPH. Additionally, NCAPH stimulates many oncogenic signaling pathways, such as β-Catenin/PD-L1, PI3K/AKT/SGK3, MEK/ERK, AURKB/AKT/mTOR, PI3K/PDK1/AKT, and Chk1/Chk2. Tumor immune microenvironment modification and tumor growth, apoptosis, metastasis, stemness, and treatment resistance all depend on these signals. NCAPH has the ability to form complexes with other proteins that are involved in glycolysis, DNA damage repair, and chromatin remodeling. This review indicates that NCAPH expression in most malignant tumors is associated with poor prognosis and low recurrence-free survival.
The research focuses on the important role of NCAPH in tumor cell proliferation, apoptosis, metastasis, stemness, rug resistance and immune response through various transcription factors and related signaling pathways. Display omitted
•The different roles of NCAPH in normal and tumor cells were elucidated. NCAPH mainly maintains cell mitosis and DNA damage repair in normal cells, whereas it promotes tumor development in tumor cells through various biological pathways.•NCAPH can stimulate multiple oncogenic signaling pathways, including PI3K/AKT/SGK3. MEK/ERK, AURKB/AKT/mTOR, PI3K/PDK1/AKT, Chk 1/Chk2, β-catenin/PD-L1, etc., which consequently affects the tumor progression through multiple biological pathways.•The expression level of NCAPH is closely related to the prognosis of clinical patients, and is a promising target for tumor therapy.
The diagnosis and management of breast cancer are undergoing a paradigm shift from a one-size-fits-all approach to an era of personalized medicine. Sophisticated diagnostics, including molecular ...imaging and genomic expression profiles, enable improved tumor characterization. These diagnostics, combined with newer surgical techniques and radiation therapies, result in a collaborative multidisciplinary approach to minimizing recurrence and reducing treatment-associated morbidity. This article reviews the diagnosis and treatment of breast cancer, including screening, staging, and multidisciplinary management.
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy that is characterized by early metastasis, low resectability, high recurrence, and therapy resistance. The experimental mouse ...models have played a central role in understanding the pathobiology of PDAC and in the preclinical evaluation of various therapeutic modalities. Different mouse models with targetable pathological hallmarks have been developed and employed to address the unique challenges associated with PDAC progression, metastasis, and stromal heterogeneity. Over the years, mouse models have evolved from simple cell line-based heterotopic and orthotopic xenografts in immunocompromised mice to more complex and realistic genetically engineered mouse models (GEMMs) involving multi-gene manipulations. The GEMMs, mostly driven by KRAS mutation(s), have been widely accepted for therapeutic optimization due to their high penetrance and ability to recapitulate the histological, molecular, and pathological hallmarks of human PDAC, including comparable precursor lesions, extensive metastasis, desmoplasia, perineural invasion, and immunosuppressive tumor microenvironment. Advanced GEMMs modified to express fluorescent proteins have allowed cell lineage tracing to provide novel insights and a new understanding about the origin and contribution of various cell types in PDAC pathobiology. The syngeneic mouse models, GEMMs, and target-specific transgenic mice have been extensively used to evaluate immunotherapies and study therapy-induced immune modulation in PDAC yielding meaningful results to guide various clinical trials. The emerging mouse models for parabiosis, hepatic metastasis, cachexia, and image-guided implantation, are increasingly appreciated for their high translational significance. In this article, we describe the contribution of various experimental mouse models to the current understanding of PDAC pathobiology and their utility in evaluating and optimizing therapeutic modalities for this lethal malignancy.
•PDAC is characterized by therapy resistance and a major impetus is on experimental therapeutics using animal models•Murine models are ideal platforms for understanding PDAC progression & pathophysiology, & testing therapeutic modalities.•Both, implantation models & GEMMs have facilitated optimization of various therapeutic approaches & enabled clinical translation.•KRAS-driven syngeneic models & their derivative tissues, tumoroids, & cell lines have accelerated PDAC immunotherapy research.•Advanced Models recapitulating metastasis, cachexia, & stromal heterogeneity will dominate the landscape of PDAC therapeutics research.
Towards precision medicine for AML Döhner, Hartmut; Wei, Andrew H; Löwenberg, Bob
Nature reviews. Clinical oncology,
09/2021, Letnik:
18, Številka:
9
Journal Article
Recenzirano
With rapid advances in sequencing technologies, tremendous progress has been made in understanding the molecular pathogenesis of acute myeloid leukaemia (AML), thus revealing enormous genetic and ...clonal heterogeneity, and paving the way for precision medicine approaches. The successful development of precision medicine for patients with AML has been exemplified by the introduction of targeted FLT3, IDH1/IDH2 and BCL-2 inhibitors. When used as single agents, these inhibitors display moderate antileukaemic activity. However, augmented clinical activity has been demonstrated when they are administered in combination with drugs with broader mechanisms of action targeting epigenetic and/or other oncogenic signalling pathways or with conventional cytotoxic agents. The development of immunotherapies has been hampered by the expression of antigens that are expressed by both leukaemic and non-malignant haematopoietic progenitor cells; nonetheless, a diverse range of immunotherapies are now entering clinical development. This myriad of emerging agents also creates challenges, such as how to safely combine agents with different mechanisms of action, the need to circumvent primary and secondary resistance, and new challenges in future clinical trial design. In this Review, we discuss the current state of precision medicine for AML, including both the potential to improve patient outcomes and the related challenges.
Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, ...characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single anti-angiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.
PI3K/AKT/mTOR pathway is one of the most important signaling pathways involved in normal cellular processes. Its aberrant activation modulates autophagy, epithelial-mesenchymal transition, apoptosis, ...chemoresistance, and metastasis in many human cancers. Emerging evidence demonstrates that some infections as well as epigenetic regulatory mechanisms can control PI3K/AKT/mTOR signaling pathway. In this review, we focused on the role of this pathway in gastric cancer development, prognosis, and metastasis, with an emphasis on epigenetic alterations including DNA methylation, histone modifications, and post-transcriptional modulations through non-coding RNAs fluctuations as well as H. pylori and Epstein-Barr virus infections. Finally, we reviewed different molecular targets and therapeutic agents in clinical trials as a potential strategy for gastric cancer treatment through the PI3K/AKT/mTOR pathway.
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