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Topic Review
Natural products as Ras inhibitors
RAS genes encode signaling proteins, which, in mammalian cells, act as molecular switches regulating critical cellular processes as proliferation, growth, differentiation, survival, motility, and metabolism in response to specific stimuli. Deregulation of Ras functions has a high impact on human health: gain-of-function point mutations in RAS genes are found in some developmental disorders and thirty percent of all human cancers, including the deadliest. For this reason, the pathogenic Ras variants represent important clinical targets against which to develop novel, effective, and possibly selective pharmacological inhibitors.  Few druggable sites have been identified for wild type and some oncogenic Ras mutants, and few natural compounds able to attenuate Ras signaling have been identified so far. Natural products represent a virtually unlimited resource of structurally different compounds from which one could draw on for this purpose, given the improvements in the isolation and screening of active molecules from complex sources, which can now be exploited for the selection of potential Ras inhibitors from natural sources. 
  • 3.0K
  • 09 Dec 2020
Topic Review
Salvage Surgery
The representative surgical intervention for unresectable stage III/IV NSCLC is salvage surgery, which refers to surgical treatment for local residual/recurrent lesions after definitive non-surgical treatment. Surgical intervention is also used for an oligometastatic stage IV NSCLC. 
  • 3.0K
  • 29 Apr 2021
Topic Review
Secondary Marine Metabolites
Secondary marine metabolites are defined as molecules with a molecular weight ranging between 100 to 1000 Da and, unlike primary marine metabolites, are often found to be unique to an organism or a specific taxonomic group of the marine source. Other than marine macroorganisms such as algae, sponges, or corals, specifically marine fungi and bacteria have shown to produce novel secondary metabolites with unique as well as diverse chemical structures that may hold the key for developing novel drugs or drug leads. Secondary marine metabolites have been found in both prokaryotic and eukaryotic microorganisms, with unicellular bacteria (e.g., Bacillus sp., Pseudomonas sp.), eukaryotic fungi (e.g., Penicillium sp., Aspergillus sp.), filamentous actinomyces (e.g., Streptomyces sp.), and terrestrial plants being the most frequently studied and versatile producers. A potential clarification why organisms produce a high assortment of bioactive secondary marine metabolites is that these molecules furnish producers with a specific advantage against competing organisms and, furthermore, act as an adaptation to ecological conditions.
  • 3.0K
  • 30 Sep 2020
Topic Review
Hypopigmented mycosis fungoides
Hypopigmented mycosis fungoides (HMF) is a variant of cutaneous T-cell lymphoma (CTCL), a heterogeneous group of extranodal non-Hodgkin’s lymphomas. HMF and classic (erythematous patch/plaque) Mycosis Fungoides (MF) display contrasting clinical characteristics: (i) HMF presents with light colored to achromic patches, as opposed to classic MF, which presents with erythematous scaly patches, plaques, tumors or erythroderma, (ii) HMF primarily affects individuals with darker skin types (Fitzpatrick phototypes IV-VI), while classic MF affects mostly Caucasians, (iii) HMF is commonly seen in pediatric/adolescents and young adults, whereas classic MF is more prevalent in elderly individuals, and (iv) the predominant malignant cells in HMF are CD8+T-cells, as opposed to CD4+T-cells in classic MF. Our recent review paper highlights that active antitumor immune response, specifically a Th1/cytotoxic antitumor immune response seen robustly in HMF, is likely responsible for the differential behavior between these two MF variants. Furthermore, we propose that the hypopigmentation (clinical sign) may serve as a surrogate marker for the presence of antitumor immune response and may portend better prognosis. 
  • 3.0K
  • 21 Oct 2020
Topic Review
Exosomes
Exosomes are lipid bilayer particles released from cells into their surrounding environment. These vesicles are mediators of near and long-distance intercellular communication and affect various aspects of cell biology. In addition to their biological function, they play an increasingly important role both in diagnosis and as therapeutic agents.
  • 3.0K
  • 20 Jan 2021
Topic Review
NK Cell Immunotherapy using Nanoparticles
Among various immunotherapies, natural killer (NK) cell cancer immunotherapy using adoptive transfer of NK cells takes a unique position by targeting tumor cells that evade the host immune surveillance. As the first-line innate effector cell, it has been revealed that NK cells have distinct mechanisms to both eliminate cancer cells directly and amplify the anticancer immune system. Over the last 40 years, NK cell cancer immunotherapy has shown encouraging reports in pre-clinic and clinic settings. In total, 288 clinical trials are investigating various NK cell immunotherapies to treat hematologic and solid malignancies in 2021. However, the clinical outcomes are unsatisfying, with remained challenges. The major limitation is attributed to the immune-suppressive tumor microenvironment (TME), low activity of NK cells, inadequate homing of NK cells, and limited contact frequency of NK cells with tumor cells. Innovative strategies to promote the cytolytic activity, durable persistence, activation, and tumor-infiltration of NK cells are required to advance NK cell cancer immunotherapy. As maturing nanotechnology and nanomedicine for clinical applications, there is a greater opportunity to augment NK cell therapeutic efficacy for the treatment of cancers. Active molecules/cytokine delivery, imaging, and physicochemical properties of nanoparticles are well equipped to overcome the challenges of NK cell cancer immunotherapy.
  • 3.0K
  • 26 Apr 2021
Topic Review
Exploiting Proteotoxic Stress in Cancer
Cancer cells typically have elevated proteotoxic stress as a result of genomic instability. The disruption of protein homeostasis causes endoplasmic reticulum stress. If not promptly managed, it could lead to a global decline in cellular function and eventual cell death[1]. This summary of review explores different protein quality control pathways and the translation of drugs targeting proteotoxic stress in haematologic cancers (using multiple myeloma as an example) versus solid cancers (using Triple Negative Breast Cancer as an example).
  • 3.0K
  • 30 Oct 2020
Topic Review
Aspartate in Cell Proliferation and Survival
Aspartate is a precursor for nucleotide synthesis and  is indispensable for cell proliferation. Moreover, the malate–aspartate shuttle plays a key role in redox balance, and a deficit in aspartate can lead to oxidative stress. It is now recognized that aspartate biosynthesis is largely governed by mitochondrial metabolism, including respiration and glutaminolysis in cancer cells. Therefore, under conditions that suppress mitochondrial metabolism, including mutations, hypoxia, or chemical inhibitors, aspartate can become a limiting factor for tumor growth and cancer cell survival.
  • 2.9K
  • 15 Jul 2022
Topic Review
Androgen Receptor Structure and Function
The Androgen Receptor (NR3C4, nuclear receptor subfamily 3, group C, gene 4) is a member of the steroid hormone group of nuclear receptors along with the oestrogen receptors (ERα and β isoforms, NR3A1 and NR2A2, respectively), glucocorticoid receptor (GR, NR3C1), progesterone receptor (PR, NR3C3) and mineralocorticoid receptor (MR, NR3C2).
  • 2.9K
  • 08 Mar 2021
Topic Review
Implementation of Lutetium-177 Therapy
Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) based radiopharmaceuticals has emerged as a therapeutic area in the field of nuclear medicine and oncology, allowing for personalized medicine. Since the first market authorization in 2018 of [¹⁷⁷Lu]Lu-DOTATATE (Lutathera®) targeting somatostatin receptor type 2 in the treatment of gastroenteropancreatic neuroendocrine tumors, intensive research has led to transfer innovative 177Lu containing pharmaceuticals to the clinic.
  • 2.9K
  • 04 May 2023
Topic Review
Bispecific Antibodies in Cancer Immunotherapy
Immunotherapy has redefined the treatment of cancer patients and it is constantly generating new advances and approaches. Among the multiple options of immunotherapy, bispecific antibodies (bsAbs) represent a novel thoughtful approach. These drugs integrate the action of the immune system in a strategy to redirect the activation of innate and adaptive immunity toward specific antigens and specific tumor locations.
  • 2.9K
  • 22 Jun 2022
Topic Review
Immunotherapy in Breast Cancer
Breast cancer is a cancer that develops from breast tissue. Symptoms of breast cancer may include a breast lump, a change in the shape of the breast, sunken skin, fluid leaking from the nipple, new sunken nipple, or red or scaly patches on the skin. Distant spread may present with bone pain, swollen lymph nodes, shortness of breath, or yellowing of the skin. Breast cancer is very complex and includes several subtypes with distinct pathological features. Most of the immunotherapy efforts have focused on the most immunogenic subtypes: triple-negative breast cancer and HER2-positive breast cancer.
  • 2.8K
  • 12 Apr 2022
Topic Review
Prostate Cancer Liquid Biopsy Biomarkers
Prostate cancer biomarkers can be measured in urine, blood or tissue. A variety of tests that analyse patients' biomarkers have been developed to improve diagnosis, prognosis and to help stratify individual's risk of prostate cancers. Liquid biopsy biomarkers are easy-to-use and non-invasive. They guide the decision-making process, determine whether the patient requires treatment or can be monitored under active surveillance, and help choose the best treatment option.
  • 2.8K
  • 29 Mar 2022
Topic Review
AP-1 Transcription Factors in Myeloma
Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. For example, AP-1 complexes containing Fra-1, Fra-2 and B-ATF play central roles in the transcriptional control of B cell development and plasma cell differentiation, while dysregulation of AP-1 family members c-Maf, c-Jun, and JunB is associated with MM cell proliferation, survival, drug resistance, bone marrow angiogenesis, and bone disease. The present review article summarizes our up-to-date knowledge on the role of AP-1 family members in plasma cell differentiation and MM pathophysiology. Moreover, it discusses novel, rationally derived approaches to therapeutically target AP-1 TFs, including protein-protein and protein-DNA binding inhibitors, epigenetic modifiers and natural products.
  • 2.8K
  • 25 May 2021
Topic Review
Molecular Glues for Cancer Treatment
Molecular glue (MG) compounds are a type of unique small molecule that can change the protein–protein interactions (PPIs) and interactomes by degrading, stabilizing, or activating the target protein after their binging. These small-molecule MGs are gradually being recognized for their potential application in treating human diseases, including cancer. Evidence suggests that small-molecule MG compounds could essentially target any proteins, which play critical roles in human disease etiology, where many of these protein targets were previously considered undruggable. Intriguingly, most MG compounds with high efficacy for cancer treatment can glue on and control multiple key protein targets. On the other hand, a single key protein target can also be glued by multiple MG compounds with distinct chemical structures. The high flexibility of MG–protein interaction profiles provides rich soil for the growth and development of small-molecule MG compounds that can be used as molecular tools to assist in unraveling disease mechanisms, and they can also facilitate drug development for the treatment of human disease, especially human cancer. 
  • 2.8K
  • 23 Jun 2022
Topic Review
Therapeutic Implications of Tumour Microenvironment
The tumour microenvironment (TME) comprises a complex ecosystem of different cell types, including immune cells, cells of the vasculature and lymphatic system, cancer-associated fibroblasts, pericytes, and adipocytes. Cancer proliferation, invasion, metastasis, drug resistance and immune escape are all influenced by the dynamic interaction between cancer cells and TME. Microbes, such as bacteria, fungi, viruses, archaea and protists, found within tumour tissues, constitute the intratumour microbiota, which is tumour type-specific and distinct among patients with different clinical outcomes. Growing evidence reveals a significant relevance of local microbiota in the colon, liver, breast, lung, oral cavity and pancreas carcinogenesis. Moreover, there is a growing interest in the tumour immune microenvironment (TIME) pointed out in several cross-sectional studies on the correlation between microbiota and TME. It is now known that microorganisms have the capacity to change the density and function of anticancer and suppressive immune cells, enabling the promotion of an inflammatory environment. As immunotherapy (such as immune checkpoint inhibitors) is becoming a promising therapy using TIME as a therapeutic target, the analysis and comprehension of local microbiota and its modulating strategies can help improve cancer treatments. 
  • 2.8K
  • 22 Aug 2022
Topic Review
Lung Cancer
Currently, lung cancer is a disease that acquired an impressive change in the clinical manangement due to the recent inovations regarding targeted therapies and immunne check point inhibitors.
  • 2.7K
  • 17 Apr 2021
Topic Review
Atypical Chronic Myeloid Leukemia
Atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML) is a rare myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) with a high rate of transformation to acute myeloid leukemia, and poor survival. Until now, the diagnosis has been based on morphological grounds only, possibly making the real frequency of the disease underestimated. Only recently, new insights in the molecular biology of MDS/MPN syndromes have deepened our knowledge of aCML, enabling us to have a better molecular profile of the disease. The knowledge gleaned from next generation sequencing has complemented morphologic and laboratory WHO criteria for myeloid neoplasms and can provide greater specificity in distinguishing aCML from alternative MDS/MPN or MPNs. The most commonly mutated genes (> 20%) in aCML are SETBP1, ASXL1, N/K-RAS, SRSF2, and TET2, and less frequently (< 10%) CBL, CSFR3, JAK2, EZH2, and ETNK1. Several of these mutations affect the JAK-STAT, MAPK, and ROCK signaling pathways, which are targetable by inhibitors that are already in clinical use and may lead to a personalized treatment of aCML patients unfit for allogeneic transplant, which is currently the only curative option for fit patients. 
  • 2.7K
  • 27 Oct 2020
Topic Review
CAR-T Cells Immunotherapies for Acute Myeloid Leukemia Therapy
The CAR is composed of four regions, namely: the extracellular antigen-binding domain usually made of a single-chain variable fragment (scFv), the hinge (the spacer region), which increases flexibility and allows the CAR to be properly matched to the target antigen, the transmembrane domain, and the intracellular signaling domain. The CAR construct was modified so as to increase the efficiency and expansion of CAR-T cells in the immunosuppressive tumor microenvironment (TME). AML is a malignancy of the hematopoietic system of a heterogeneous nature. The disease is caused by mutations resulting in the proliferation of cancer cells derived from progenitor cells of the myeloid lineage.
  • 2.7K
  • 01 Jun 2023
Topic Review
Sacituzumab Govitecan in Breast Cancer
Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment.
  • 2.7K
  • 07 Dec 2021
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