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Topic Review
Molecular Mechanisms of Oncolytic Newcastle Disease Virus
Oncolytic viruses represent interesting anti-cancer agents with high tumor selectivity and immune stimulatory potential. The anti-neoplastic activities of Newcastle Disease Virus (NDV) include (i) the endocytic targeting of the GTPase Rac1 in Ras-transformed human tumorigenic cells; (ii) the switch from cellular protein to viral protein synthesis and the induction of autophagy mediated by viral nucleoprotein NP; (iii) the virus replication mediated by viral RNA polymerase (large protein (L), associated with phosphoprotein (P)); (iv) the facilitation of NDV spread in tumors via the membrane budding of the virus progeny with the help of matrix protein (M) and fusion protein (F); and (v) the oncolysis via apoptosis, necroptosis, pyroptosis, or ferroptosis associated with immunogenic cell death. A special property of this oncolytic virus consists of its potential for breaking therapy resistance in human cancer cells.
  • 702
  • 29 Mar 2022
Topic Review
Nanoplatform for Delivery of Topotecan in Cancer Milieu
Chemotherapy has been the predominant treatment modality for cancer patients, but its overall performance is still modest. Difficulty in penetration of tumor tissues, a toxic profile in high doses, multidrug resistance in an array of tumor types, and the differential architecture of tumor cells as they grow are some of the bottlenecks associated with the clinical usage of chemotherapeutics. Advances in tumor biology understanding and the emergence of novel targeted drug delivery tools leveraging various nanosystems offer hope for developing effective cancer treatments. Topotecan is a topoisomerase I inhibitor that stabilizes the transient TOPO I-DNA cleavable complex, leading to single-stranded breaks in DNA. Due to its novel mechanism of action, TOPO is reported to be active against various carcinomas, namely small cell lung cancer, cervical cancer, breast cancer, and ovarian cancer. Issues of cross-resistance with numerous drugs, rapid conversion to its inactive form in biological systems, appended adverse effects, and higher water solubility limit its therapeutic efficacy in clinical settings. Topotecan nanoformulations offer several benefits for enhancing the therapeutic action of this significant class of chemotherapeutics. The likelihood that the target cancer cells will be exposed to the chemotherapeutic drug while in the drug-sensitive s-phase is increased due to the slow and sustained release of the chemotherapeutic, which could provide for a sustained duration of exposure of the target cancer cells to the bioavailable drug and result in the desired therapeutic outcome. 
  • 701
  • 11 Jan 2023
Topic Review
Biology of Glioblastoma Multiforme
Glioblastoma multiforme (GBM) represents a highly aggressive malignancy of the brain which leads to early patient lethality. Malignant GBM cells develop from glia and gradually acquire specific mutations and epigenetic changes associated with several disctinct phenotypic features such as differently expressed and localized cytoskeletal components (in particular microtubules) and deregulated cell cycle via defunct checkpoints. While the use of traditional microtubular targeting agents (eg. taxanes) in treatment of GBM is limited due to several reasons, newly repurpused compounds such as benzimidazole carbamates may offer a new perspective by inducing mitotic catastrophe in GBM. Mitotic catastrophe is nowadays viewed as a way of elimination of genomically unstable cells via diverse cellular endpoint phenotypes and its exploration in potential treatment of GBM is the subject of this entry.
  • 700
  • 27 Oct 2020
Topic Review
Non-Small-Cell Lung Cancer Signaling Pathways
Treatment of advanced (metastatic) non-small-cell lung cancer (NSCLC) is currently mainly based on immunotherapy with antibodies against PD-1 or PD-L1, alone, or in combination with chemotherapy. In locally advanced NSCLC and in early resected stages, immunotherapy is also employed. Tumor PD-L1 expression by immunohistochemistry is considered the standard practice. Response rate is low, with median progression free survival very short in the vast majority of studies reported. Herein, numerous biological facets of NSCLC are described involving driver genetic lesions, mutations ad fusions, PD-L1 glycosylation, ferroptosis and metabolic rewiring in NSCLC and lung adenocarcinoma (LUAD). Novel concepts, such as immune-transmitters and the effect of neurotransmitters in immune evasion and tumor growth, the nascent relevance of necroptosis and pyroptosis, possible new biomarkers, such as gasdermin D and gasdermin E, the conundrum of K-Ras mutations in LUADs, with the growing recognition of liver kinase B1 (LKB1) and metabolic pathways, including others, are also commented.
  • 700
  • 09 Oct 2020
Topic Review
Rectal Cancer
Locally advanced rectal cancer represents a major health problem. Recently, the important results obtained with RAPIDO and PRODIGE 23 trials have changed the treatment algorithm of this disease.
  • 700
  • 22 Dec 2020
Topic Review
Anticancer Phytochemicals and Their Structure
Cancer is a challenging disease and is the main cause of mortality worldwide; however, its impact is not evenly distributed. The cancer burden in developed and underdeveloped countries has increased over time owing to a variety of factors, including aging and growing populations, rapid socioeconomic growth, and changes in the incidence of risk factors. Since ancient times, plant-based medicines have been employed in clinical practice and have yielded good results. The modern research system and advanced screening techniques for plants’ bioactive constituents have enabled phytochemical discovery for the prevention and treatment of challenging diseases such as cancer. 
  • 700
  • 30 May 2022
Topic Review
Nanoparticles-Based Platforms Targeting the PD-1/PD-L1 Pathway
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis showed remarkable improvements in overall response and patient survival, which changed the treatment landscape for multiple cancer types. PD-1/PD-L1-targeted agents encapsulated in nanoparticles have emerged as novel drug delivery systems for improving the delivery efficacy, enhancing immune response and minimizing side effects in cancer treatment. Nanocarriers targeting the PD-1/PD-L1 axis showed enhanced functionalities and improved technical weaknesses based on their reduced off-target effects, biocompatible properties, multifunctional potential and biomimetic modifications. 
  • 700
  • 24 Aug 2022
Topic Review
DNA Methylation in Cancer
DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation is strongly implicated in cancer development. Cancers possess an extensively hypomethylated genome with focal regions of hypermethylation at CPG islands. Due to the highly conserved nature of cancer-specific methylation, its detection in cell-free DNA in plasma using liquid biopsies constitutes an area of interest in biomarker research. The advent of next-generation sequencing and newer computational technologies have allowed for the development of diagnostic and prognostic biomarkers that utilize methylation profiling to diagnose disease and stratify risk. Methylome-based predictive biomarkers can determine the response to anti-cancer therapy. An additional emerging application of these biomarkers is in minimal residual disease monitoring. Several key challenges need to be addressed before cfDNA-based methylation biomarkers become fully integrated into practice. The first relates to the biology and stability of cfDNA. The second concerns the clinical validity and generalizability of methylation-based assays, many of which are cancer type-specific. The third involves their practicability, which is a stumbling block for translating technologies from bench to clinic. 
  • 700
  • 26 Jan 2024
Topic Review
ROS in Cancer Cell Metabolism
Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts.
  • 699
  • 22 Sep 2021
Topic Review
Integrin Alpha v Beta 6  in Cancer Treatment
Integrins are necessary for cell adhesion, migration, and positioning. Essential for inducing signalling events for cell survival, proliferation, and differentiation, they also trigger a variety of signal transduction pathways involved in mediating invasion, metastasis, and squamous-cell carcinoma. Several recent studies have demonstrated that the up- and down-regulation of the expression of αv and other integrins can be a potent marker of malignant diseases and patient prognosis.
  • 699
  • 31 Oct 2022
Topic Review
Two-Dimensional Theranostic Nanomaterials in Cancer
As the combination of therapies enhances the performance of biocompatible materials in cancer treatment, theranostic therapies are attracting increasing attention rather than individual approaches.
  • 698
  • 18 Feb 2021
Topic Review
Cancer Metastasis
Despite great advances in the detailed profiling of tumor cells and the development of therapeutic agents, cancer metastasis is still a big hurdle in the treatment of cancer patients. This is possibly because tumor cells plastically evolve through interplay with the host environment, including stromal cells, vascular cells, and immune cells. The reciprocal evolution among the numerous components further increases the heterogeneity and complexity in both tumor cells and the host, leading to refractory cancer. It is important to better understand the entire metastatic cascade and the practical implementations targeting the oncoimmune drivers in the mechanisms.
  • 698
  • 24 Feb 2021
Topic Review
Human Endogenous Retroviruses (HERVs）
Human Endogenous Retroviruses (HERVs) are accounting for 8% of the human genome. These sequences are remnants from ancient germline infections by exogenous retroviruses. After million years of evolution and multiple integrations, HERVs have acquired many damages rendering them defective. At steady state, HERVs are mostly localized in the heterochromatin and silenced by methylation. Multiple conditions have been described to induce their reactivation, including auto-immune diseases and cancers. HERVs re-expression leads to RNA (simple and double-stranded) and DNA production (by reverse transcription), modulating the innate immune response. Some studies also argue for a role of HERVs in shaping the evolution of innate immunity, notably in the development of the interferon response. However, their exact role in the innate immune response, particularly in cancer, remains to be defined. In this review, we see how HERVs could be key-players in mounting an antitumor immune response.
  • 698
  • 03 Jun 2021
Topic Review
State-of-the-Art of Glioblastoma Treatment
Glioblastoma is the most frequent and lethal primary tumor of the central nervous system. Through many years, research has brought various advances in glioblastoma treatment. Glioblastoma management is based on maximal safe surgical resection, radiotherapy, and chemotherapy with temozolomide. Bevacizumab has been added to the treatment arsenal for the recurrent scenario. Despite the great efforts in therapeutic research, glioblastoma management has suffered minimal changes, and the prognosis remains poor. Combined therapeutic strategies and delivery methods, including immunotherapy, synthetic molecules, natural compounds, and glioblastoma stem cell inhibition, may potentiate the standard of care therapy and represent the next step in glioblastoma management research.
  • 698
  • 15 Jul 2022
Topic Review
Current Challenges in Breast Implantation
Breast implantation (BI) is the most common plastic surgery worldwide performed among women. Generally, BI is performed both in aesthetic and oncoplastic procedures. 
  • 698
  • 18 Aug 2022
Topic Review
Near Infrared Photoimmunotherapy
Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses an antibody-photoabsorber (IRDye700DX) conjugate (APC) that is activated by NIR light irradiation. A major benefit of NIR-PIT is that only APC-bound cancer cells that are exposed to NIR light are killed by NIR-PIT; thus, minimal damage occurs in adjacent normal cells. NIR-PIT has now been applied to many cancers expressing various cell-surface target proteins using monoclonal antibodies designed to bind to them. Moreover, NIR-PIT is not limited to tumor antigens but can also be used to kill specific host cells that create immune-permissive environments in which tumors grow. Moreover, multiple targets can be treated simultaneously with NIR-PIT using a cocktail of APCs. NIR-PIT has great potential to treat a wide variety of cancers by targeting appropriate tumor cells, immune cells, or both, and can be augmented by other immunotherapies. 
  • 697
  • 23 Jun 2021
Topic Review
CRISPR/Cas9 in Breast Cancer Therapeutic
Breast cancer is one of the most prevalent forms of cancer globally and is among the leading causes of death in women. Its heterogenic nature is a result of the involvement of numerous aberrant genes that contribute to the multi-step pathway of tumorigenesis. Despite the fact that several disease-causing mutations have been identified, therapy is often aimed at alleviating symptoms rather than rectifying the mutation in the DNA sequence. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 is a groundbreaking tool that is being utilized for the identification and validation of genomic targets bearing tumorigenic potential. CRISPR/Cas9 supersedes its gene-editing predecessors through its unparalleled simplicity, efficiency and affordability.
  • 697
  • 06 Jun 2021
Topic Review
The Vascular Microenvironment in Glioblastoma
Glioblastoma multiforme, the deadliest primary brain tumor, is characterized by an excessive and aberrant neovascularization. The initial expectations raised by anti-angiogenic drugs were soon tempered due to their limited efficacy in improving the overall survival. Intrinsic resistance and escape mechanisms against anti-VEGF therapies evidenced that tumor angiogenesis is an intricate multifaceted phenomenon and that vessels not only support the tumor but exert indispensable interactions for resistance and spreading. 
  • 697
  • 20 Jun 2022
Topic Review
Insights about MYC and Apoptosis in B-Lymphomagenesis
The balance between cell survival and cell death represents an essential part of human tissue homeostasis, while altered apoptosis contributes to several pathologies and can affect the treatment efficacy. Impaired apoptosis is one of the main cancer hallmarks and some types of lymphomas harbor mutations that directly affect key regulators of cell death (such as BCL-2 family members). The development of novel techniques in the field of immunology and new animal models has greatly accelerated our understanding of oncogenic mechanisms in MYC-associated lymphomas. Mouse models are a powerful tool to reveal multiple genes implicated in the genesis of lymphoma and are extensively used to clarify the molecular mechanism of lymphoma, validating the gene function. Key features of MYC-induced apoptosis will be discussed here along with more recent studies on MYC direct and indirect interactors, including their cooperative action in lymphomagenesis. We review our current knowledge about the role of MYC-induced apoptosis in B-cell malignancies, discussing the transcriptional regulation network of MYC and regulatory feedback action of miRs during MYC-driven lymphomagenesis. More importantly, the finding of new modulators of apoptosis now enabling researchers to translate the discoveries that have been made in the laboratory into clinical practice to positively impact human health.  
  • 696
  • 19 Jun 2020
Topic Review
Applications of Liquid Biopsy in Colorectal Cancer Screening
Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current screening methods (either endoscopic or stool-based tests) also require disagreeable preparation protocols and tissue sampling through invasive procedures, rendering adherence to CRC screening programs suboptimal. In this context, the necessity for novel, less invasive biomarkers able to identify and assess cancer at an early stage is evident. Liquid biopsy comes as a promising minimally invasive diagnostic tool, able to provide comprehensive information on tumor heterogeneity and dynamics during carcinogenesis.
  • 696
  • 17 Nov 2022
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