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Topic Review
Hypoxia-Driven Effects in Cancer
Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo-, radio-, and immunotherapy. The depletion of oxygen in proliferating and advanced tumors causes an array of genetic, transcriptional, and metabolic adaptations that promote survival, metastasis, and a clinically malignant phenotype. At the nexus of these interconnected pathways are hypoxia-inducible factors (HIFs) which orchestrate transcriptional responses under hypoxia. We discuss mechanisms and pathways, such as HIF signaling, mitochondrial dynamics, exosomes, and the unfolded protein response, that contribute to hypoxia-induced phenotypic changes.
  • 1.0K
  • 02 Jun 2021
Topic Review
GOF Mutant p53 in Cancers
TP53 is mutated in the majority of human cancers. Mutations can lead to loss of p53 expression or expression of mutant versions of the p53 protein. These mutant p53 proteins have oncogenic potential. They can inhibit any remaining WTp53 in a dominant negative manner, or they can acquire new functions that promote tumour growth, invasion, metastasis and chemoresistance.
  • 1.0K
  • 17 Nov 2022
Topic Review
Peptide Receptor Radionuclide Therapy
The PRRT (Peptide Receptor Radionuclide Therapy) is a promising modality treatment for patients with inoperable or metastatic neuroendocrine tumors (NETs). Progression-free survival (PFS) and overall survival (OS) of these patients are favorably comparable with standard therapies. The protagonist in this type of therapy is a somatostatin-modified peptide fragment ([Tyr3] octreotide), equipped with a specific chelating system (DOTA) capable of creating a stable bond with β-emitting radionuclides, such as yttrium-90 and lutetium-177.
  • 1.0K
  • 04 Oct 2021
Topic Review
CTLA-4
Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are limited at the moment to a minority of patients and there is a need for a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind with higher affinity to CD80 and CD86 than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap. 
  • 1.0K
  • 13 Apr 2021
Topic Review
ING Genes in NSCLC
Carcinogenic mutations allow cells to escape governing mechanisms that commonly inhibit uncontrolled cell proliferation and maintain tightly regulated homeostasis between cell death and survival. Members of the inhibition of growth (ING) family act as tumor suppressors, governing cell cycle, apoptosis and cellular senescence. The molecular mechanism of action of ING genes, as well as their anchor points in pathways commonly linked to malignant transformation of cells, have been studied with respect to a variety of cancer specimens.
  • 1.0K
  • 23 Aug 2021
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. 
  • 1.0K
  • 23 Jun 2021
Topic Review
Deep Learning for Computational Histopathology
The histopathological image is widely considered as the gold standard for the diagnosis and prognosis of human cancers. Recently, deep learning technology has been extremely successful in the field of computer vision, which has also boosted considerable interest in digital pathology analysis. Deep learning and its extensions have opened several avenues to tackle many challenging histopathological image analysis problems including color normalization, image segmentation, and the diagnosis/prognosis of human cancers.
  • 1.0K
  • 11 Mar 2022
Topic Review
Timing of Metastatic Colorectal Cancer
Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, where ~50% of patients develop metastasis, despite current improved management. Genomic characterisation of metastatic CRC, and elucidating the effects of therapy on the metastatic process, are essential to help guide precision medicine. Multi-region whole-exome sequencing was performed on 191 sampled tumour regions of patient-matched therapy-naïve and treated CRC primary tumours (n = 92 tumour regions) and metastases (n = 99 tumour regions), in 30 patients. Somatic variants were analysed to define the origin, composition, and timing of seeding in the metastatic progression of therapy-naïve and treated metastatic CRC. High concordance, with few genomic differences, was observed between primary CRC and metastases. Most cases supported a late dissemination model, via either monoclonal or polyclonal seeding. Polyclonal seeding appeared more common in therapy-naïve metastases than in treated metastases. Whereby, treatment prompted for the selection of distinct resistant clones, through monoclonal seeding to distant metastatic sites. Overall, this study reinforces the importance of early clinical detection and surgical excision of the CRC tumour, whilst further highlighting the clinical challenges for metastatic CRC with increased intratumour heterogeneity (either due to early dissemination or polyclonal metastatic spread) and the underlying risk of future therapeutic resistance in treated patients.
  • 1.0K
  • 20 Oct 2020
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.
  • 1.0K
  • 23 Apr 2023
Topic Review
The Golgi Apparatus as an Anticancer Therapeutic Target
The Golgi apparatus (GA) is a central hub in our cells, helping modify and move proteins and lipids. When the GA does not work correctly, it can affect cell processes linked to cancer. This dysregulation can impact how proteins are changed, where they go in and outside the cell, how cells use energy, or even the structure of the extracellular matrix and the environment. That is why targeting the GA could be an appealing approach to treat cancer. Surprisingly, there are no anticancer drugs approved that specifically target the GA.
  • 1.0K
  • 03 Jan 2024
Topic Review
Epidemiology of Young Age of Onset Breast Cancer
Breast cancer (BC) in young women is poorly understood and understudied in the literature. We need to design cohorts of breast cancer patients with young age of onset to study this particular group of patients better. 
  • 1.0K
  • 24 Apr 2023
Topic Review
FGF/FGFR Signaling in Hepatocellular Carcinoma
As the most common primary liver cancer, HCC is a tricky cancer resistant to systemic therapies. The fibroblast growth factor family and its receptors are gaining more and more attention in various cancers. Noticing an explosion in the number of studies about aberrant FGF/FGFR signaling in HCC being studied, we were encouraged to summarize them.
  • 1.0K
  • 25 May 2021
Topic Review
IPSC-Based PDAC Models and Immunotherapies
Advances in the treatment of pancreatic ductal adenocarcinoma (PDAC) using neoadjuvant chemoradiotherapy, chemotherapy, and immunotherapy have had minimal impact on the overall survival of patients. A general lack of immunogenic features and a complex tumor microenvironment (TME) are likely culprits for therapy refractoriness in PDAC. Induced pluripotent stem cells (iPSCs) should be explored as a means to advance the treatment options for PDAC, by providing representative in vitro models of pancreatic cancer development. In addition, iPSCs could be used for tailor-made cellular immunotherapies or as a source of tumor-associated antigens in the context of vaccination.
  • 1.0K
  • 29 Mar 2022
Topic Review
Gal-9/TIM-3 Immune Checkpoint with α-Lactose
The disaccharide lactose is an excipient commonly used in pharmaceutical products. The two anomers, α- and β-lactose (α-L/β-L), differ by the orientation of the C-1 hydroxyl group on the glucose unit. In aqueous solution, a mutarotation process leads to an equilibrium of about 40% α-L and 60% β-L at room temperature.
  • 1.0K
  • 04 Jan 2022
Topic Review
Immuno-PET
“Immuno-PET” merges the high target selectivity and specificity of antibodies and engineered fragments toward a given tumor cell surface marker with the high spatial resolution, sensitivity, and quantitative capabilities of positron emission tomography (PET) imaging techniques. In this review, we detail and provide examples of the clinical limitations of current imaging techniques for diagnosing PDAC. 
  • 1.0K
  • 06 May 2021
Topic Review
Application of mRNA Technology in Cancer Therapeutics
mRNA-based therapeutics pose as promising treatment strategies for cancer immunotherapy. Improvements in materials and technology of delivery systems have helped to overcome major obstacles in generating a sufficient immune response required to fight a specific type of cancer. Several in vivo models and early clinical studies have suggested that various mRNA treatment platforms can induce cancer-specific cytolytic activity, leading to numerous clinical trials to determine the optimal method of combinations and sequencing with already established agents in cancer treatment.
  • 1.0K
  • 02 Sep 2022
Topic Review
Tumor Microenvironment in Basal and Squamous Cell Carcinoma
It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively.
  • 1.0K
  • 11 May 2023
Topic Review
Biomarkers for Hepatocellular Carcinoma Diagnosis/Prognosis
Hepatocellular carcinoma (HCC) causes many deaths worldwide, and current treatments have limitations. Immunotherapies have shown the most promising clinical outcomes for advanced HCC. However, there are many patients with HCC who still respond poorly to these treatments. Circulating biomarkers that can easily be obtained through blood sampling are promising in predicting treatment responses, since they are minimally invasive and enable us to constantly monitor disease progression. 
  • 1.0K
  • 28 Sep 2021
Topic Review
Diffuse Intrinsic Pontine Gliomas
Diffuse intrinsic pontine gliomas are malignant brain tumors which arise from the pons in children. These tumors are incurable and nearly all the patients die within a year after diagnosis. 
  • 1.0K
  • 19 Apr 2021
Topic Review
Orexins/Hypocretins and Cancer
Orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role.
  • 1.0K
  • 03 Sep 2021
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