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Topic Review
Metabolic Reprogramming in Cancer Cells
Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. Altered metabolic flux in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, and other regulatory molecules, including non-coding RNAs. Changes to metabolic pathways in cancer are dynamic, exhibit plasticity, and are often dependent on the type of tumor and the tumor microenvironment, leading in a shift of thought from the Warburg Effect and the “reverse Warburg Effect” to metabolic plasticity. 
  • 1.8K
  • 27 Jul 2021
Topic Review
Cobalamin-Dependent Metabolism and Its Implication in Solid Cancers
Cobalamin or vitamin B12 (B12) is a cofactor for methionine synthase and methylmalonyl-CoA mutase, two enzymes implicated in key pathways for cell proliferation: methylation, purine synthesis, succinylation and ATP production. Ensuring these functions in cancer cells therefore requires important cobalamin needs and its uptake through the transcobalamin II receptor (TCII-R). 
  • 1.8K
  • 13 Jun 2022
Topic Review
Phosphorylation in Chronic Myeloid Leukemia
Protein phosphorylation is a fundamental mechanism for many intracellular processes underlying cell life. This reversible mechanism, which is triggered by intra- and extra-cellular signals, regulates metabolism, transcription, proliferation, differentiation, cell movements, and apoptosis in countless cellular functions. Protein kinases form an enzyme family that catalyzes the transfer of the gamma-phosphate of adenosine triphosphate (ATP) to specific hydroxyl amino acids in protein substrates. On the other hand, protein phosphatases regulate the action of kinases, playing the role of regulators in the phosphorylation processes. The present investigation summarize the current knowledge on the roles playd by phosphatases in Chronic Myeloid Leukemia (CML).
  • 1.7K
  • 02 Jun 2021
Topic Review
Non-Muscle-Invasive Bladder Cancer
Non-muscle-invasive bladder cancer (NMIBC) is characterized by a high rate of cure, but also by a non-negligible probability of recurrence and risk progression to muscle-invasive disease. NMIBC management requires a proper local resection and staging, followed by a risk-based treatment with intravesical agents. For many years, the current gold standard treatment for patients with intermediate or high-risk disease is transurethral resection of the bladder (TURB) followed by intravesical bacillus Calmette–Guérin (BCG) instillations. Unfortunately, in about half of high-risk patients, intravesical BCG treatment fails and NMIBC persists or recurs early. While radical cystectomy remains the gold standard for these patients, new therapeutic targets are being individuated and studied. Radical cystectomy in fact can provide an excellent long-term disease control, but can deeply interfere with quality of life. In particular, the enhanced immune checkpoints expression shown in BCG-unresponsive patients and the activity of immune checkpoints inhibitors (ICIs) in advanced bladder cancer provided the rationale for testing ICIs in NMIBC. Recently, pembrolizumab has shown promising activity in BCG-unresponsive NMIBC patients, obtaining FDA approval. Meanwhile multiple novel drugs with alternative mechanisms of action have proven to be safe and effective in NMIBC treatment and others are under investigation.
  • 1.7K
  • 29 Mar 2022
Topic Review
Tetraspanin CD81
Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop (EC2) for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. 
  • 1.7K
  • 14 Apr 2023
Topic Review
EphA2 Signaling in tumors
The Eph receptors represent the largest group among Receptor Tyrosine kinase (RTK) families. The Eph/ephrin signaling axis plays center stage during development, and the deep perturbation of signaling consequent to its dysregulation in cancer reveals the multiplicity and complexity underlying its function. In the last decades, they have emerged as key players in solid tumors, including colorectal cancer (CRC). EphA2 is involved in tumor progression and resistance to therapy.
  • 1.7K
  • 18 Mar 2021
Topic Review
Myeloid Neoplasms
Myeloid neoplasms encompass a very heterogeneous family of diseases characterized by the failure of the molecular mechanisms that ensure a balanced equilibrium between hematopoietic stem cells (HSCs) self-renewal and the proper production of differentiated cells. The origin of the driver mutations leading to preleukemia can be traced back to HSC/progenitor cells. Many properties typical to normal HSCs are exploited by leukemic stem cells (LSCs) to their advantage, leading to the emergence of a clonal population that can eventually progress to leukemia with variable latency and evolution. In fact, different subclones might in turn develop from the original malignant clone through accumulation of additional mutations, increasing their competitive fitness. This process ultimately leads to a complex cancer architecture where a mosaic of cellular clones—each carrying a unique set of mutations—coexists. The repertoire of genes whose mutations contribute to the progression toward leukemogenesis is broad. It encompasses genes involved in different cellular processes, including transcriptional regulation, epigenetics (DNA and histones modifications), DNA damage signaling and repair, chromosome segregation and replication (cohesin complex), RNA splicing, and signal transduction. Among these many players, transcription factors, RNA splicing proteins, and deubiquitinating enzymes are emerging as potential targets for therapeutic intervention. 
  • 1.7K
  • 23 Aug 2021
Topic Review
P53 DNA Binding Cooperativity Mutations
p53 is a tumor suppressor that is mutated in half of all cancers. The high clinical relevance has made p53 a model transcription factor for delineating general mechanisms of transcriptional regulation. p53 forms tetramers that bind DNA in a highly cooperative manner. The DNA binding cooperativity of p53 has been studied by structural and molecular biologists as well as clinical oncologists. These experiments have revealed the structural basis for cooperative DNA binding and its impact on sequence specificity and target gene spectrum. Cooperativity was found to be critical for the control of p53-mediated cell fate decisions and tumor suppression. Importantly, an estimated number of 34,000 cancer patients per year world-wide have mutations of the amino acids mediating cooperativity, and knock-in mouse models have confirmed such mutations to be tumorigenic. While p53 cancer mutations are classically subdivided into “contact” and “structural” mutations, “cooperativity” mutations form a mechanistically distinct third class that affect the quaternary structure but leave DNA contacting residues and the three-dimensional folding of the DNA-binding domain intact. In this review we discuss the concept of DNA binding cooperativity and highlight the unique nature of cooperativity mutations and their clinical implications for cancer therapy.
  • 1.7K
  • 23 Jun 2021
Topic Review
SFKs in intestine
Src, originally identified as an oncogene, is a membrane-anchored tyrosine kinase (TK) and the Src family kinase (SFK) prototype. SFKs regulate the signalling induced by a wide range of cell surface receptors leading to epithelial cell growth and adhesion. In the intestine, the SFK members Src, Fyn and Yes regulate epithelial cell proliferation and migration during tissue regeneration and transformation, thus implicating conserved and specific functions. In patients with colorectal cancer (CRC), SFK activity is a marker of poor clinical prognosis and a potent driver of metastasis formation. These tumorigenic activities are linked to SFK capacity to promote the dissemination and tumour-initiating capacities of epithelial tumour cells. However, it is unclear how SFKs promote colon tumour formation and metastatic progression because SFK-encoding genes are unfrequently mutated in human cancer. Here, we review recent findings on SFK signalling during intestinal homeostasis, regeneration and tumorigenesis, and discuss about therapeutic strategies to efficiently target Src signalling in CRC
  • 1.7K
  • 03 Aug 2020
Topic Review
MNT
MNT (MAX’s Next Tango) is a crucial modulator of MYC, controls several cellular functions, and is activated in most human cancers. It is the largest, most divergent, and most ubiquitously expressed protein of the MXD family. MNT was first described as a MYC antagonist and tumor suppressor. Indeed, 10% of human tumors present deletions of one MNT allele. However, some reports show that MNT functions in cooperation with MYC by maintaining cell proliferation, promoting tumor cell survival, and supporting MYC-driven tumorigenesis in cellular and animal models. Although MAX was originally considered MNT’s obligate partner, it is also known that heterodmerize with MLX. Recent findings demonstrate that MNT can also work independently, as MNT forms homodimers and interacts with proteins both outside and inside of the proximal MYC network, as REL. These complexes are involved in a wide array of cellular processes, from transcriptional repression via SIN3 to the modulation of metabolism through MLX as well as immunity and apoptosis via REL.
  • 1.7K
  • 02 Oct 2021
Topic Review
Role of Zinc in Breast Cancer Tumorigenesis
It is well-known that serum and cellular concentrations of zinc are altered in breast cancer patients. Specifically, there are notable zinc hyper-aggregates in breast tumor cells when compared to normal mammary epithelial cells.
  • 1.7K
  • 09 Dec 2022
Topic Review
Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients
Neuroblastoma is the most common extracranial solid tumor of childhood, with a median age at diagnosis of 17 months. Its incidence is 10.2 cases per million children aged <15 years. Neuroblastoma arises in tissues of the sympathetic nervous system, mostly in the adrenal medulla or paraspinal ganglia. It appears as a mass in the abdomen, pelvis, neck, or chest, with about half of the patients having metastatic disease at diagnosis. The presence of metastatic diseases over the age of 12 or 18 months and aggressive biological features (e.g., MYCN oncogene amplification) define high-risk neuroblastoma. The prognosis for such patients is poor, with a long-term survival rate of only 40%.
  • 1.7K
  • 07 Jan 2022
Topic Review
The Short-Chain Fatty Acids
Through fermentation, the gut microbiota can produce several types of metabolites, including short-chain fatty acids (SCFAs). SCFAs play an important role in maintaining epithelial barrier functions and intestinal homeostasis. 
  • 1.7K
  • 27 Oct 2022
Topic Review
Sorcin in cancer drug resistance
The development of drug resistance is one of the main causes of failure in anti-cancer treatments. Tumor cells adopt many strategies to counteract the action of chemotherapeutic agents, e.g., enhanced DNA damage repair, inactivation of apoptotic pathways, alteration of drug targets, drug inactivation, and overexpression of ABC (Adenosine triphosphate-binding cassette, or ATP-binding cassette) transporters. These are broad substrate-specificity ATP-dependent efflux pumps able to export toxins or drugs out of cells; for instance, ABCB1 (MDR1, or P-glycoprotein 1), overexpressed in most cancer cells, confers them multidrug resistance (MDR). The gene coding for sorcin (SOluble Resistance-related Calcium-binding proteIN) is highly conserved among mammals and is located in the same chromosomal locus and amplicon as the ABC transporters ABCB1 and ABCB4, both in human and rodent genomes (two variants of ABCB1, i.e., ABCB1a and ABCB1b, are in rodent amplicon). Sorcin was initially characterized as a soluble protein overexpressed in multidrug (MD) resistant cells and named “resistance-related” because of its co-amplification with ABCB1.
  • 1.7K
  • 21 Dec 2020
Topic Review
Vimentin at the Heart of Epithelial Mesenchymal Transition
Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. 
  • 1.7K
  • 22 Oct 2021
Topic Review
Segmentectomy for Lung Cancer
A lung segmentectomy, a type of sublobar resection, preserves more pulmonary function than is lobectomy. The use of minimally invasive lung segmentectomy for early-stage lung cancer has been increasing. This procedure is associated with technical challenges because (1) it requires a thorough understanding of the complex segmental anatomy that frequently accompanies anomalies, and (2) it is difficult to confirm the location of small tumors during minimally invasive surgery, which makes it difficult to obtain adequate surgical margins. 
  • 1.7K
  • 22 Jul 2021
Topic Review
Radiation Therapy
Tumor radioresistance is associated with a failure to achieve loco-regional disease control following radiotherapy with the highest acceptable doses. Radiobiology research focused on tumor radioresistance has pointed out several mechanisms attenuating the efficacy of tumor irradiation and several treatment answers to overcome such radio-resistance. Personalized medecine allows us to adapt the treatment to diseases according to patient specificities and characteristics. Novel radiotherapy such as heavy ion therapy enable a better balance between high doses to the tumor and low doses to the surrounding healthy tissues.
  • 1.7K
  • 23 Oct 2020
Topic Review
Fisetin in Cancer
Fisetin is a flavonoid naturally occurring in various plants that possesses anticancer activity. It has the power to stop cancers from growing quickly, becoming invasive, and spreading to multiple tissues.
  • 1.7K
  • 10 May 2023
Topic Review
Antitumor Action of Mango Peel
Today, an improved understanding of cancer cell response to cellular stress has become more necessary. Indeed, targeting the intracellular pro-oxidant/antioxidant balance triggering the tumor commitment to cell demise could represent an advantageous strategy to develop cancer-tailored therapies. Ethanolic extracts from Mangifera indica L. have been proved to possess anti-tumor properties in many cancer systems. However, although most effects have been demonstrated with fruit pulp extract, the underlying molecular mechanisms of mango peel are still unclear. This research was undertaken to explore the effects of mango peel extract (MPE) on colon cancer cell lines. Data obtained demonstrated that MPE can affect the cell viability of three colon cancer cell lines (HT29, Caco-2 and HCT116), inducing an imbalance of cellular redox responses. A consistent decline in thiol group content, which was accompanied by upregulation of MnSOD—a mitochondrial scavenger enzyme that modulates the cellular response against oxidative damage- was observed. Such an effect was the consequence of an early production of mitochondrial superoxide anions that appeared after just 30 min of exposure of colon cancer cells to MPE. The effect was accompanied by mitochondrial injury, consisting of the dissipation of mitochondrial membrane potential and a decrease in the level of proteins localized in the mitochondrial membrane (VDAC1, mitofilin, and some members of Bcl-2 family) —with the mitochondrial release of apoptogenic factors (cytochrome C and AIF). The analysis of the cytotoxic effects exerted by the different constituents of MPE (gallic acid, mangiferin, citric acid, quinic acid, pentagalloyl glucose, and methyl gallate) allowed us to identify those phytochemicals responsible for the observed anticancer effects, sustaining their future employment as chemopreventive or therapeutic agents.
  • 1.7K
  • 04 Aug 2021
Topic Review
Claudins and Gastric Cancer
Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial–mesenchymal transition (EMT) and cell–cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell–cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18–ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. 
  • 1.7K
  • 10 Jan 2022
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