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Topic Review
3D Pancreatic Cancer Models
Pancreatic cancer is an extremely lethal malignancy with a survival rate lower than any other cancer type. For decades, two-dimensional (2D) cultures have been the cornerstone for studying cancer cell biology and drug testing, due to their simplicity and cost. However, their inability to reconstitute the tumor architecture, the absence of nutrient and oxygen supply gradients, as well as the lack of appropriate mechano-forces that mimic the extracellular microenvironment, make them an inadequate model to accurately reproduce tissue level-specific characteristics. Bioengineering systems, such as three-dimensional (3D) patient-specific models, are progressively emerging as systems better able to mimic the biology of pancreatic tumors and to test new anticancer therapies, as they more efficiently recapitulate the complex tumor microenvironment characteristic of pancreatic tumors.
  • 1.3K
  • 22 Mar 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.
  • 1.3K
  • 15 Jul 2022
Topic Review
Photochemical Internalization
Photochemical internalization (PCI) is a further development of photodynamic therapy (PDT). In this report, we describe PCI as a potential tool for cellular internalization of chemotherapeutic agents or antigens and systematically review the ongoing research. One Phase-I clinical trial has been conducted, and it demonstrated that PCI-mediated bleomycin treatment was safe and identified tolerable doses of the photosensitizer disulfonated tetraphenyl chlorin (TPCS2a). Likewise, PCI was pre-clinically shown to mediate major histocompatibility complex (MHC) class I antigen presentation and generation of tumor-specific cytotoxic CD8+ T-lymphocytes (CTL) and cancer remission. A first clinical Phase I trial with the photosensitizer TPCS2a combined with human papilloma virus antigen (HPV) was recently completed and results are expected in 2020. Hence, photosensitizers and light can be used to mediate cytosolic delivery of endocytosed chemotherapeutics or antigens. While the therapeutic potential in cancer has been clearly demonstrated pre-clinically, further clinical trials are needed to reveal the true translational potential of PCI in humans.
  • 1.3K
  • 16 Jun 2021
Topic Review
BRAF Mutated Colorectal Cancer
Colon cancer is one of the most frequently diagnosed malignancies in adults, considering both its incidence and prevalence. Anatomically, the right colon is considered as being from the cecum to the splenic flexure, and the left colon is from the splenic flexure to the rectum. Sidedness is a surrogate of a wide spectrum of colorectal cancer (CRC) biology features (embryology, microbiome, methylation, microsatellite instability (MSI), BRAF, aging, KRAS, consensus molecular subtypes (CMS), etc.), which result in prognostic factors. Different molecular subtypes have been identified, according to genomic and transcriptomic criteria. A subgroup harboring a BRAF mutation has been described, and represents approximately 10% of the patients diagnosed with colon cancer. This subgroup has morphological, clinical, and therapeutic characteristics that differ substantially from patients who do not carry this genetic alteration. Unfortunately, there is no established standard of care for this particular cohort of patients.
  • 1.3K
  • 14 Sep 2020
Topic Review
ECM Remodeling in Tumor Microenvironment
Tumorigenesis is characterized by an uncontrolled proliferation of cells that have usually undergone genetic mutations due to hereditary, environmental, and lifestyle factors. Cancer progression, persistent inflammation of the surrounding tissue, and extracellular matrix (ECM) remodeling are three highly interconnected processes. Indeed, a multifaceted network of inflammatory signals produced by cancer cells and innate immune cells recruited in the tumor microenvironment (TME) induce changes in the surrounding stroma that, in turn, influence the homeostasis of ECM, creating a “cancerized” microenvironment that supports tumor growth and metastasis. The ECM represents a well-organized and heterogeneous network of macromolecules that provides a mechanical scaffold to the cells and mediates the diffusion of signaling molecules to sustain cell functions.
  • 1.3K
  • 26 Aug 2021
Topic Review
Neoantigen-Reactive T Cells
Neoantigens are mutated proteins that arise from tumor-specific mutations.
  • 1.3K
  • 16 Dec 2021
Topic Review
Keep Calm and Carry on with Extra Centrosomes
Aberrations in the centrosome number and structure can readily be detected at all stages of tumor progression and are considered hallmarks of cancer. Centrosome anomalies are closely linked to chromosome instability and, therefore, are proposed to be one of the driving events of tumor formation and progression. This concept, first posited by Boveri over 100 years ago, has been an area of interest to cancer researchers.
  • 1.3K
  • 10 Feb 2022
Topic Review
Structure and Function of UHRF1
Cancer is one of the leading causes of death worldwide, and its incidence and mortality are increasing each year. Improved therapeutic strategies against cancer have progressed, but remain insufficient to invert this trend. Along with several other risk factors, abnormal genetic and epigenetic regulations play a critical role in the initiation of cellular transformation, as well as tumorigenesis. The epigenetic regulator UHRF1 (ubiquitin-like, containing PHD and RING finger domains 1) is a multidomain protein with oncogenic abilities overexpressed in most cancers. Through the coordination of its multiple domains and other epigenetic key players, UHRF1 regulates DNA methylation and histone modifications. This well-coordinated dialogue leads to the silencing of tumor-suppressor genes (TSGs) and facilitates tumor cells’ resistance toward anticancer drugs, ultimately promoting apoptosis escape and uncontrolled proliferation. Several studies have shown that the downregulation of UHRF1 with natural compounds in tumor cells induces the reactivation of various TSGs, inhibits cell growth, and promotes apoptosis.
  • 1.3K
  • 24 Aug 2023
Topic Review
Exosomes and Extracellular Vesicles
Exosomes are endosome-derived nanovesicles produced by healthy as well as diseased cells. Their proteic, lipidic and nucleic acid composition is related to the cell of origin, and by vehiculating bioactive molecules they are involved in cell-to-cell signaling, both in healthy and pathologic conditions. Being nano-sized, non-toxic, biocompatible, scarcely immunogenic, and possessing targeting ability and organotropism, exosomes have been proposed as nanocarriers for their potential application in diagnosis and therapy. Among the different techniques exploited for exosome isolation, the sequential ultracentrifugation/ultrafiltration method seems to be the gold standard; alternatively, commercially available kits for exosome selective precipitation from cell culture media are frequently employed. To load a drug or a detectable agent into exosomes, endogenous or exogenous loading approaches have been developed, while surface engineering procedures, such as click chemistry, hydrophobic insertion and exosome display technology, allow for obtaining actively targeted exosomes. 
  • 1.3K
  • 23 Jan 2021
Topic Review
Talimogene Laherparepvec
Talimogene laherparepvec (T-VEC), an attenuated HSV expressing GM-CSF, became the first oncolytic agent that achieved regulatory approval in the United States, Europe, and Australia. 
  • 1.3K
  • 09 Feb 2023
Topic Review
SMYD3
The SMYD3 methyltransferase has been found overexpressed in several types of cancers of the gastrointestinal (GI) tract. While high levels of SMYD3 have been positively correlated with cancer progression in cellular and advanced mice models, suggesting it as a potential risk and prognosis factor, its activity seems dispensable for autonomous in vitro cancer cell proliferation. We first describe the oncogenic activity of SMYD3 as a transcriptional activator of genes involved in tumorigenesis, cancer development and transformation and as a co-regulator of key cancer-related pathways. Then, we dissect its role in orchestrating cell cycle regulation and DNA damage response (DDR) to genotoxic stress by promoting homologous recombination (HR) repair, thereby sustaining cancer cell genomic stability and tumor progression. Based on this evidence and on the involvement of PARP1 in other DDR mechanisms, we also outline a synthetic lethality approach consisting of the combined use of SMYD3 and PARP inhibitors, which recently showed promising therapeutic potential in HR-proficient GI tumors expressing high levels of SMYD3. Overall, these findings identify SMYD3 as a promising target for drug discovery.
  • 1.3K
  • 14 Sep 2021
Topic Review
Anatomical Resection
Anatomical resection (AR), described as systematic removal of a liver segment confined by tumor-bearing portal tributaries, may improve survival by reducing the risk of tumor recurrence compared with non-AR.
  • 1.3K
  • 22 Feb 2021
Topic Review
Amino Acids in Cancer
Cancer metabolism is an emerging field of investigation aimed at identifying cancer cell vulnerabilities in order to define novel anti-cancer therapeutic approaches based on interventions that modulate the availability of specific nutrients. Amino acids (AAs) are used by cancer cells as both building blocks for protein synthesis required for rapid tumor growth and as sources of energy. 
  • 1.3K
  • 06 Dec 2022
Topic Review
Significance of Mitochondrial-Dysfunction in Cancer
       Mitochondria are semi-autonomous intracellular double membrane-bound organelles, which include an outer membrane, a highly folded inner membrane (crista), a matrix space surrounded by the inner membrane, and an inter-membrane space between the inner and outer membranes. Usually, a cell has hundreds or thousands of mitochondria, which can occupy up to 25% of the cellular cytoplasm. Mitochondria are a convergence point for glucose, glutamine, and lipid metabolism. The primary function of mitochondria is to support the TCA cycle and aerobic respiration by oxidative phosphorylation, generating ATP through the mitochondrial respiratory chain to fulfill the energy needs for cell survival. One unique feature of mitochondria is that they possess their own supercoiled, double-stranded circular genetic material called mitochondrial DNA (mtDNA) that encodes rRNAs, tRNAs, and proteins essential for electron transport and oxidative phosphorylation, as well as their own genetic repair mechanisms. Mitochondrial biogenesis requires the coordinated expression of both mtDNA- and nuclear DNA-encoded genes. Thirteen proteins are encoded by mtDNA, while approximately 1000 mitochondrial proteins are encoded by the nuclear genome, translated in the cytoplasm and transported into the mitochondria by a specific transport system. These two pools of proteins are required to maintain mitochondria as a cellular power hub and a signaling nexus that are essential for normal cell function. Defects in many of the mitochondrial components are causal for a multitude of cellular diseases. Of note, the reprogramming of cellular metabolism and the aberrant redox status have been heralded as major emerging hallmarks of neoplastic transformation. Overall, mitochondrial dysfunction caused by mtDNA mutations, malfunctioned TCA cycle enzymes, electron respiratory chain leakage and subsequent oxidative stress, and/or aberrant oncogenic and tumor suppressor signaling is known to alter cellular metabolic pathways, disrupt redox balance, and cause resistance to apoptosis and therapies that significantly contribute to the development of multiple types of human cancers. In the following sections, we will present current knowledge on these aspects of mitochondrial dysfunction pertaining to the pathologies of various forms of human malignancies.
  • 1.3K
  • 27 Aug 2020
Topic Review
Dendritic Cell Extracellular Vesicles
Dendritic cells have a central role in starting and regulating immune functions in anticancer responses. The crosstalk of dendritic cells with tumors and other immune cell subsets is partly mediated by extracellular vesicles (EVs) secreted by both cell types and is multidirectional. In the case of dendritic cell EVs, the presence of stimulatory molecules and their ability to promote tumor antigen-specific responses, have raised interest in their uses as therapeutics vehicles.
  • 1.3K
  • 17 Dec 2020
Topic Review
Acute Promyelocytic Leukemia in Children
Acute promyelocytic leukemia (APL) represents a paradigm of precision medicine.
  • 1.3K
  • 07 May 2021
Topic Review
Tripartite Motif Family
The tripartite motif (TRIM) family comprises at least 80 members in humans, with most having ubiquitin or SUMO E3 ligase activity conferred by their N-terminal RING domain. TRIMs regulate a wide range of processes in ubiquitination- or sumoylation-dependent manners in most cases, and fewer as adaptors. Their roles in the regulation of viral infections, autophagy, cell cycle progression, DNA damage and other stress responses, and carcinogenesis are being increasingly appreciated, and their E3 ligase activities are attractive targets for developing specific immunotherapeutic strategies for immune diseases and cancers.
  • 1.3K
  • 22 Sep 2021
Topic Review
RAS Mutations in Thyroid Cancer
The significance of RAS mutations as a prognostic marker has changed in recent years. At the beginning, RAS mutations were considered a promoter of progressive dedifferentiation in benign nodules, and as such a risk factor for evolution from adenoma to carcinoma, therefore a marker of poorer prognosis in DTC. It is clear now that the impact of RAS mutations on thyroid cell, normal and transformed, and the impact on the clinical behavior of thyroid neoplasms must not to be considered by itself but rather together with other genetic abnormalities in a more complex contest.
  • 1.3K
  • 30 Aug 2021
Topic Review
Carbon Fiber Implants in Orthopaedic Oncology
Carbon fiber offers numerous material benefits including reduced wear, high strength-to-weight ratio, a similar elastic modulus to that of bone, and high biocompatibility. Carbon fiber implants are increasingly used in multiple arenas within orthopaedic surgery, including spine, trauma, arthroplasty, and oncology. In the orthopaedic oncologic population, the radiolucency of carbon fiber facilitates post-operative imaging for tumor surveillance or recurrence, the monitoring of bony healing and union, and radiation mapping and delivery.
  • 1.3K
  • 12 Oct 2022
Topic Review
Major Advances and Emerging Concepts of EPR-Enhancing Strategies
The enhanced permeability and retention (EPR) effect is dynamic and a phenomenon of tumor blood vessels, which is mostly dependent on blood flow. Animal models of solid tumors rich in blood flow demonstrated enhanced EPR effects. The strategies to enhance the EPR effect can be broadly classified into pharmacological and physical-based approaches.
  • 1.3K
  • 03 Mar 2023
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