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Topic Review
Targeted Therapies for Gastric Cancer
Many phase III trials failed to demonstrate a survival benefit from the addition of molecular therapy to conventional chemotherapy for advanced and metastatic gastric cancer, and only three agents were approved by the FDA. Despite recent advances in surgical techniques and in anticancer drugs, and the adoption of perioperative treatments mostly based on conventional chemotherapy, the prognosis of advanced and metastatic gastric cancer remains poor. In the last decade, the addition of molecular therapy did not show any significant survival advantage, and the first reports available documented an increase of the rate of severe adverse effects and related mortality. The survival benefits of molecular therapies available to date for advanced and metastatic gastric cancer are rather unclear, mostly due to inaccurate patient selection, particularly concerning oncogene amplification and copy number.
  • 923
  • 28 Sep 2021
Topic Review
Epigenetic Alterations in Salivary Gland Tumors
Salivary gland carcinomas (SGCs) are a diverse collection of malignant tumors with marked differences in biological activity, clinical presentation and microscopic appearance. Although the etiology is varied, secondary radiation, oncogenic viruses as well as chromosomal rearrangements have all been linked to the formation of SGCs. Epigenetic modifications are any heritable changes in gene expression that are not caused by changes in DNA sequence. It is widely accepted that epigenetics plays an important role in SGC development.
  • 923
  • 16 Jun 2023
Topic Review
ALT Positivity in Human Cancers
Neoplastic cells typically activate one of the two Telomere Maintenance Mechanisms(TMM) to maintain their telomeres during uncontrolled proliferation. Most tumors reactivatetelomerase, a high-fidelity DNA transferase with reverse transcriptase activity. The prevalence of telomerase positive cancers is at 80–90% of all malignancies. A significant percentage of neoplasias activate the second type of TMM, called alternativelengthening of telomeres (ALT), to achieve replicative immortality and telomereelongation. ALT is commonly thought to occur in about 10–20% of all tumors. Unlike the TEL+ tumors, which rely on the enzymatic activity of a single enzyme,ALT relies on many DNA damage response (DDR) proteins, including those involved inthe homology-dependent repair (HDR) pathway.
  • 922
  • 23 Jun 2021
Topic Review
SARS-CoV-2 and Cancer Cross-Talk
Since the pandemic’s onset, a growing population of individuals has recovered from SARS-CoV-2 infection and its long-term effects in some of the convalescents are gradually being reported. Although the precise etiopathogenesis of post-acute COVID-19 sequelae (PACS) remains elusive, the mainly accepted rationale is that SARS-CoV-2 exerts long-lasting immunomodulatory effects, promotes chronic low-grade inflammation, and causes irreversible tissue damage. Several viruses have been causally linked to human oncogenesis, whereas chronic inflammation and immune escape are thought to be the leading oncogenic mechanisms. Excessive cytokine release, impaired T-cell responses, aberrant activation of regulatory signaling pathways (e.g., JAK-STAT, MAPK, NF-kB), and tissue damage, hallmarks of COVID-19 disease course, are also present in the tumor microenvironment. Therefore, the intersection of COVID-19 and cancer is partially recognized and the long-term effects of the virus on oncogenesis and cancer progression have not been explored yet.
  • 922
  • 03 Nov 2022
Topic Review
Current Treatment of Glioblastoma
Glioblastoma (GBM) is the most common form of primary malignant brain tumor with a devastatingly poor prognosis. The disease does not discriminate, affecting adults and children of both sexes, and has an average overall survival of 12–15 months, despite advances in diagnosis and rigorous treatment with chemotherapy, radiation therapy, and surgical resection. In addition, most survivors will eventually experience tumor recurrence that only imparts survival of a few months. GBM is highly heterogenous, invasive, vascularized, and almost always inaccessible for treatment. Based on all these outstanding obstacles, there have been tremendous efforts to develop alternative treatment options that allow for more efficient targeting of the tumor including small molecule drugs and immunotherapies. A number of other strategies in development include therapies based on nanoparticles, light, extracellular vesicles, and micro-RNA, and vessel co-option. Advances in these potential approaches shed a promising outlook on the future of GBM treatment.
  • 922
  • 22 Sep 2021
Topic Review
FOXO3, Autophagy and Sorafenib Resistance in Human Hepatocarcinoma
Early development of resistance to sorafenib accounts for the poor prognosis of advanced hepatocarcinoma (HCC). Autophagy, a double-edge autodegradative and recycling process, has been related to the modulation of drug sensitivity in cancer cells. The transcription factor forkhead box O3 (FOXO3) has been associated with the pathogenesis of HCC, but the involvement of FOXO3 on autophagy-related sorafenib resistance in HCC needs to be further investigated. A recent research verified that HCC cells are able to surpass sorafenib effects during chemoresistance acquisition via the upregulation of FOXO3 and the subsequent induction of a pro-survival autophagy. Hence, FOXO3-associated autophagy could constitute a novel therapeutic target in the advanced HCC landscape.
  • 921
  • 26 Nov 2021
Topic Review
Extracellular Matrix Environment of ccRCC
The extracellular matrix (ECM) controls fundamental properties of tumors, including growth, blood vessel investment, and invasion. The ECM defines rigidity of tumor tissue and individual ECM proteins have distinct biological effects on tumor cells. The most frequent initiating genetic mutation in ccRCC (clear cell renal cell carcinoma) inactivates the VHL gene, which plays a direct role in organizing the ECM.
  • 921
  • 15 Sep 2022
Topic Review
Neurofibromatosis Type 1-Associated Gliomas
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that affects children and adults. Individuals with NF1 are at high risk for central nervous system neoplasms including gliomas. The purpose of this review is to discuss the spectrum of intracranial gliomas arising in individuals with NF1 with a focus on recent preclinical and clinical data.
  • 921
  • 25 Jun 2021
Topic Review
CA125 and Ovarian Cancer
 The tumour biomarker CA125 has been used as a biomarker for ovarian cancer detection and progression.
  • 920
  • 12 Jan 2021
Topic Review
FOXO3 as a Novel Biomarker in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) represents one of the main causes of cancer-related death worldwide. The transcription factor forkhead box O3 (FOXO3) has been related to hepatic diseases and tumor progression, but the exact role played by FOXO3 on HCC still remains unclear. Recently, a novel systematic review with meta-analysis revealed the potential diagnostic and prognostic value of FOXO3 in this primary liver cancer type.
  • 920
  • 05 Nov 2021
Topic Review
Hypoxic Cells for Tumor Radiotherapy
Radiation therapy plays an increasingly important role in cancer treatment. It can inhibit the progression of various cancers through radiation-induced DNA breakage and reactive oxygen species (ROS) overload. Unfortunately, solid tumors, such as breast and lung cancer, often develop a hypoxic microenvironment due to insufficient blood supply and rapid tumor proliferation, thereby affecting the effectiveness of radiation therapy. Restraining hypoxia and improving the curative effect of radiotherapy have become difficult problems. Ferroptosis is a new type of cell death caused by lipid peroxidation due to iron metabolism disorders and ROS accumulation.
  • 920
  • 16 May 2022
Topic Review
Irreversible Electroporation in Oncology
Locoregional therapies play an ever-increasing role in contemporary oncology. Researchers provide an up-to-date, informed analysis of locoregional therapies harnessing electric pulses. Irreversible electroporation (IRE), gene electrotransfer (GET), electrochemotherapy (ECT), calcium electroporation (Ca-EP), and tumour-treating fields (TTF) are integral to the therapeutic strategy in several solid tumours, ranging from skin cancers to visceral and bone metastases.
  • 919
  • 30 Jun 2023
Topic Review
Cellular Prion Protein
Studies on the cellular prion protein (PrPC) have been actively conducted because misfolded PrPC is known to cause transmissible spongiform encephalopathies or prion disease. PrPC is a glycophosphatidylinositol‐anchored cell surface glycoprotein that has been reported to affect several cellular functions such as stress protection, cellular differentiation, mitochondrial homeostasis, circadian rhythm, myelin homeostasis, and immune modulation. Recently, it has also been reported that PrPC mediates tumor progression by enhancing the proliferation, metastasis, and drug resistance of cancer cells. In addition, PrPC regulates cancer stem cell properties by interacting with cancer stem cell marker proteins. In this review, we summarize how PrPC promotes tumor progression in terms of proliferation, metastasis, drug resistance, and cancer stem cell properties. In addition, we discuss strategies to treat tumors by modulating the function and expression of PrPC via the regulation of HSPA1L/HIF‐1α expression and using an anti‐prion antibody.
  • 918
  • 10 Dec 2020
Topic Review
Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer
Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%.
  • 918
  • 21 Sep 2022
Topic Review
Parvovirus-Based Combinatorial Cancer Immunotherapy
Resistance to anticancer treatments poses continuing challenges to oncology researchers and clinicians. The underlying mechanisms are complex and multifactorial. However, the immunologically “cold” tumor microenvironment (TME) has recently emerged as one of the critical players in cancer progression and therapeutic resistance. Therefore, TME modulation through induction of an immunological switch towards inflammation (“warming up”) is among the leading approaches in modern oncology. Oncolytic viruses (OVs) are seen today not merely as tumor cell-killing (oncolytic) agents, but also as cancer therapeutics with multimodal antitumor action. Due to their intrinsic or engineered capacity for overcoming immune escape mechanisms, warming up the TME and promoting antitumor immune responses, OVs hold the potential for creating a proinflammatory background, which may in turn facilitate the action of other (immunomodulating) drugs. This review deals with the smallest among all OVs, the H-1 parvovirus (H-1PV), and focuses on H-1PV-based combinatorial approaches, whose efficiency has been proven in preclinical and/or clinical settings. Special focus is given to cancer types with most devastating impact on life expectancy that urgently call for novel therapies.
  • 917
  • 11 Oct 2021
Topic Review
CAR T-Cells for CNS Lymphoma
Primary or secondary central nervous system (CNS) lymphoma is frequently associated with a poor prognosis. CAR T-cells are being established as a relevant treatment approach in hematological B-cell malignancies. Unfortunately, most clinical studies on chimeric antigen-receptor (CAR) T-cells have excluded patients with CNS involvement but several clinical trials on CAR T-cell therapy in CNS lymphoma patients are currently ongoing. Preclinical and preliminary clinical data suggest an overall acceptable safety profile and considerable anti-tumor effects might be extrapolated for CAR T-cell therapy in CNS lymphoma. 
  • 917
  • 01 Jun 2021
Topic Review
Designer T and NK Cells in Glioblastoma Immunotherapy
Glioblastoma (GBM) is the most prevalent, aggressive primary brain tumour with a dismal prognosis. Gene editing technologies are a game changer, enabling design of novel molecular-immunological treatments to be used in combination with chemoradiation, to achieve long lasting survival benefits for patients. Designer T and NK cells are a modality within immunotherapy that manipulates receptor-ligand interactions to enhance cells of the immune system to destroy cancer more effectively. Patient’s own immune cells are isolated, genetically modified to improve responses against cancer cells, expanded, and subsequently reintroduced into the individual.
  • 917
  • 29 Mar 2022
Topic Review
LRS for Surgical Breast Cancer
Laser Raman spectroscopy (LRS) is a highly specific biomolecular technique which has been shown to have the ability to distinguish malignant and normal breast tissue. This paper discusses significant advancements in the use of LRS in surgical breast cancer diagnosis, with an emphasis on statistical and machine learning strategies employed for precise, transparent and real-time analysis of Raman spectra. When combined with a variety of “machine learning” techniques LRS has been increasingly employed in oncogenic diagnostics. This paper proposes that the majority of these algorithms fail to provide the two most critical pieces of information required by the practicing surgeon: a probability that the classification of a tissue is correct, and, more importantly, the expected error in that probability. Stochastic backpropagation artificial neural networks inherently provide both pieces of information for each and every tissue site examined by LRS. If the networks are trained using both human experts and an unsupervised classification algorithm as gold standards, rapid progress can be made understanding what additional contextual data is needed to improve network classification performance. Our patients expect us to not simply have an opinion about their tumor, but to know how certain we are that we are correct. Stochastic networks can provide that information.
  • 917
  • 25 Nov 2020
Topic Review
Role of p53 and TAp73 in Neuroblastoma
Neuroblastoma is the most common extracranial pediatric tumor. Although children with low- and intermediate-risk neuroblastoma, which correspond to approximately half of all newly diagnosed cases, have a good event-free and overall survival, high-risk neuroblastoma can be extremely aggressive and hard-to-treat tumors. In neuroblastoma, p53 and TAp73 act as safeguards against malignant transformation, but they are commonly inhibited by negative regulators, such as MDMs, Itch, and Aurora kinase A.
  • 917
  • 18 Jan 2023
Topic Review
Molecular Epidemiology across Cancer Types in Microsatellite Instability
Microsatellite instability (MSI) occurs in a wide variety of tumor types and is one of the most important predictive biomarkers for immune checkpoint inhibitor therapy.
  • 917
  • 23 Apr 2023
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