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Topic Review
Smoothened-Dependent/-Independent Hedgehog Signaling Pathway
The Hedgehog (Hh)-glioma-associated oncogene homolog (GLI) signaling pathway is highly conserved among mammals, with crucial roles in regulating embryonic development as well as in cancer initiation and progression. The GLI transcription factors (GLI1, GLI2, and GLI3) are effectors of the Hh pathway and are regulated via Smoothened (SMO)-dependent and SMO-independent mechanisms. The SMO-dependent route involves the common Hh-PTCH-SMO axis, and mutations or transcriptional and epigenetic dysregulation at these levels lead to the constitutive activation of GLI transcription factors. Conversely, the SMO-independent route involves the SMO bypass regulation of GLI transcription factors by external signaling pathways and their interacting proteins or by epigenetic and transcriptional regulation of GLI transcription factors expression. Both routes of GLI activation, when dysregulated, have been heavily implicated in tumorigenesis of many known cancers, making them important targets for cancer treatment. 
  • 1.5K
  • 15 Sep 2021
Topic Review
Measurable Residual Disease in AML
Relapse is still a major problem in AML because it occurs in about 60–80% of patients, even those who have previously achieved complete remission (CR), defined by the presence of ≤5% bone marrow (BM) leukemic cells. Thus, since CR is unable to predict the relapse risk, significantly more sensitive techniques aimed at identifying AML cells in BM or peripheral blood, a parameter termed measurable residual disease (MRD), have been developed. Among them, RT-qPCR, which analyses appropriate molecular markers, and multiparameter flow cytometry (MFC), which analyses aberrantly expressed antigens, have been identified as the methods of choice for MRD detection. 
  • 1.5K
  • 22 Sep 2021
Topic Review
Gastric Intestinal Metaplasia
Gastric cancer (GC) remains one of the most common causes of mortality worldwide. Intestinal metaplasia (IM) is one of the preneoplastic gastric lesions and is considered an essential predisposing factor in GC development. Here we present a review of recent most relevant papers to summarize major findings on the molecular alterations in gastric IM. The latest progress in novel diagnostic methods allows scientists to identify various types of molecular alterations in IM, such as polymorphisms in various genes, changes in the expression of micro-RNAs and long noncoding RNAs, and altered microbiome profiles. The results have shown that some of these alterations have strong associations with IM and a potential to be used for screening, treatment, and prognostic purposes; however, one of the most important limiting factors is the inhomogeneity of the studies. Therefore, further large-scale studies and clinical trials with standardized methods designed by multicenter consortiums are needed. As of today, various molecular alterations in IM could become a part of personalized medicine in the near future, which would help us deliver a personalized approach for each patient and identify those at risk of progression to GC.
  • 1.5K
  • 24 Jun 2021
Topic Review
Cancer-Associated Gangliosides as Tumor Markers
Aberrant expression of glycosphingolipids is a hallmark of cancer cells and is associated with their malignant properties. Disialylated gangliosides GD2 and GD3 are considered as markers of tumors from neuroectoderm origin, whereas fucosyl-GM1 is expressed in very few normal tissues but overexpressed in a variety of cancers, especially in small cell lung carcinoma. These gangliosides are absent in most normal adult tissues, making them targets of interest in immuno-oncology. Passive and active immunotherapy strategies have been developed and have shown promising results in clinical trials.
  • 1.5K
  • 22 Jun 2021
Topic Review
Macrophage
Macrophages within solid tumors and metastatic sites are heterogenous populations with different developmental origins and substantially contribute to tumor progression. A number of tumor-promoting phenotypes associated with both tumor- and metastasis-associated macrophages are similar to innate programs of embryonic-derived tissue-resident macrophages. In contrast to recruited macrophages originating from marrow precursors, tissue-resident macrophages are seeded before birth and function to coordinate tissue remodeling and maintain tissue integrity and homeostasis. Both recruited and tissue-resident macrophage populations contribute to tumor growth and metastasis and are important mediators of resistance to chemotherapy, radiation therapy, and immune checkpoint blockade. Thus, targeting various macrophage populations and their tumor-promoting phenotypes holds therapeutic promise.
  • 1.5K
  • 25 May 2021
Topic Review
Classifying Oligometastatic Non-Small Cell Lung Cancer
Oligometastatic non-small cell lung cancer (NSCLC) represents a subset of patients with limited metastatic spread and the potential for achieving long-term survival, or even cure, with LCT to all sites of disease. Patient selection for aggressive local treatment of oligometastatic NSCLC would be facilitated by a common definition of what constitutes oligometastasis. The definition of oligometastasis by LCT treatment feasibility is vague and elusive, particularly in the context of ever-improving local treatment modalities.
  • 1.5K
  • 10 Dec 2021
Topic Review
Gut and Intratumoral Microbiomes in Tumor Metastasis
Cancer cell dissemination involves invasion, migration, resistance to stressors in the circulation, extravasation, colonization, and other functions responsible for macroscopic metastases. By enhancing invasiveness, motility, and intravasation, the epithelial-to-mesenchymal transition (EMT) process promotes the generation of circulating tumor cells and their collective migration. Preclinical and clinical studies have documented intensive crosstalk between the gut microbiome, host organism, and immune system. According to the findings, polymorphic microbes might play diverse roles in tumorigenesis, cancer progression, and therapy response. Microbial imbalances and changes in the levels of bacterial metabolites and toxins promote cancer progression via EMT and angiogenesis. In contrast, a favorable microbial composition, together with microbiota-derived metabolites, such as short-chain fatty acids (SCFAs), can attenuate the processes of tumor initiation, disease progression, and the formation of distant metastases.
  • 1.5K
  • 15 Apr 2024
Topic Review
Lamin A/C in Disease/Cancer
Lamin A/C is a nuclear protein with multiple functions in normal and diseased cells. As lamin A/C has a variety of critical roles within the cell, mutations of the lamin A/C gene and incorrect processing of the protein results in a wide variety of diseases, ranging from striated muscle disorders to accelerated aging diseases.
  • 1.5K
  • 25 Feb 2021
Topic Review
Novel Selective RET Inhibitors
RET-selective tyrosine kinase inhibitors (TKIs) pralsetinib and selpercatinib, are effective against the RET V804L/M gatekeeper mutants. However, adaptive mutations that cause resistance at the solvent front RET G810 residue have been found, pointing to the need for the development of the next-generation of RET-specific TKIs. 
  • 1.5K
  • 29 Apr 2021
Topic Review
Peptide Drug Conjugates in Cancer Therapy
Drug conjugates have become a significant focus of research in the field of targeted medicine for cancer treatments. Peptide-drug conjugates (PDCs), a subset of drug conjugates, are composed of carrier peptides ranging from 5 to 30 amino acid residues, toxic payloads, and linkers that connect the payload to the peptide. PDCs are further broken down into cell-penetrating peptides (CPPs) and cell-targeting peptides (CTPs), each having their own differences in the delivery of cytotoxic payloads. Generally, PDCs as compared to other drug conjugates—like antibody-drug conjugates (ADCs)—have advantages in tumor penetration, ease of synthesis and cost, and reduced off-target effects. Further, as compared to traditional cancer treatments (e.g., chemotherapy and radiation), PDCs have higher specificity for the target cancer with generally less toxic side effects in smaller doses. 
  • 1.5K
  • 19 Jan 2023
Topic Review
ACHP Targets the STAT3
STAT3 is an oncogenic transcription factor that regulates the expression of genes which are involved in malignant transformation. Aberrant activation of STAT3 has been observed in a wide range of human malignancies and its role in negative prognosis is well-documented. In this report, we performed high-throughput virtual screening in search of STAT3 signaling inhibitors using a cheminformatics platform and identified 2-Amino-6-[2-(Cyclopropylmethoxy)-6-Hydroxyphenyl]-4-Piperidin-4-yl Nicotinonitrile (ACHP) as the inhibitor of the STAT3 signaling pathway. The predicted hit was evaluated in non-small cell lung cancer (NSCLC) cell lines for its STAT3 inhibitory activity. In vitro experiments suggested that ACHP decreased the cell viability and inhibited the phosphorylation of STAT3 on Tyr705 of NSCLC cells. In addition, ACHP imparted inhibitory activity on the constitutive activation of upstream protein tyrosine kinases, including JAK1, JAK2, and Src. ACHP decreased the nuclear translocation of STAT3 and downregulated its DNA binding ability. Apoptosis was evidenced by cleavage of caspase-3 and PARP with the subsequent decline in antiapoptotic proteins, including Bcl-2, Bcl-xl, and survivin. Overall, we report that ACHP can act as a potent STAT3 signaling inhibitor in NSCLC cell lines.
  • 1.5K
  • 28 Oct 2020
Topic Review
Tumor Microenvironment in melanoma
Antitumor therapies have made great strides in recent decades. Chemotherapy, aggressive and unable to discriminate cancer from healthy cells, has given way to personalized treatments that, recognizing and blocking specific molecular targets, have paved the way for targeted and effective therapies. Melanoma was one of the first tumor types to benefit from this new care frontier by introducing specific inhibitors for v-Raf murine sarcoma viral oncogene homolog B (BRAF), mitogen-activated protein kinase (MEK), v-kit Hardy–Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and, recently, immunotherapy. However, despite the progress made in the melanoma treatment, primary and/or acquired drug resistance remains an unresolved problem. The molecular dynamics that promote this phenomenon are very complex but several studies have shown that the tumor microenvironment (TME) plays, certainly, a key role. In this review, we will describe the new melanoma treatment approaches and we will analyze the mechanisms by which TME promotes resistance to targeted therapy and immunotherapy.
  • 1.5K
  • 21 Oct 2020
Topic Review
Extracellular Vesicles (EVs)
Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs’ stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. 
  • 1.4K
  • 18 Sep 2020
Topic Review
Cancer Immunotherapy and Delivery System
Immunotherapy is a powerful clinical strategy for the treatment of various diseases, including cancer, and an understanding of cancer immunology is important to the optimization of this strategy to achieve higher efficacy. 
  • 1.4K
  • 15 Aug 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. 
  • 1.4K
  • 24 Aug 2022
Topic Review
Gemtuzumab ozogamicin
       Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated to calicheamicin, a cytotoxic antitumor antibiotic. GO is indicated for the treatment of newly-diagnosed or relapsed/refractory CD33-positive acute myeloid leukemia (AML).
  • 1.4K
  • 30 Oct 2020
Topic Review
Chemotherapy-Induced Dysbiosis and Neurocognitive Disorders
While lifesaving achievements allowed for cancer cure in many patients, cancer survivors may suffer from long-term adverse effects substantially altering their quality of life and reintegration into normal life. Chemotherapy damages the intestinal mucosa and heavily disrupts the gut ecosystem leading to gastrointestinal toxicity. Increasing evidence from animal models and clinical studies demonstrated the associations between intestinal dysbiosis and depression, anxiety, pain, and impaired cognitive functions. Recently, the emerging role of the microbiome in chemotherapy-induced late effects affecting cognitive functions in cancer survivors has been proposed. 
  • 1.4K
  • 11 Mar 2021
Topic Review
Breast-Conserving Surgery
Breast-conserving surgery’s main goal is to fully remove the tumor with clear margins, while avoiding resection of healthy breast tissue in order to achieve better cosmetic results. 
  • 1.4K
  • 22 Feb 2021
Topic Review
Environmental Remediation of Antineoplastic Drugs
The global burden of cancer is on the rise, and as a result, the number of therapeuticsadministered for chemotherapy is increasing. The occupational exposure, recalcitrant nature andecotoxicological toxicity of these therapeutics, referred to as antineoplastic (ANP) drugs, have raisedconcerns about their safe remediation. This review provides an overview of the environmental sourceof ANPs agents, with emphasis on the currently used remediation approaches. Outpatient excreta,hospital euents, and waste from pharmaceutical industries are the primary source of ANP waste.The current review describes various biotic and abiotic methods used in the remediation of ANPdrugs in the environment. Abiotic methods often generate transformation products (TPs) of unknowntoxicity. In this light, obtaining data on the environmental toxicity of ANPs and its TPs is crucial todetermine their toxic e ect on the ecosystem. We also discuss the biodegradation of ANP drugs usingmonoculture of fungal and bacterial species, and microbial consortia in sewage treatment plants.The current review e ort further explores a safe and sustainable approach for ANP waste treatmentto replace existing chemical and oxidation intensive treatment approaches. To conclude, we assessthe possibility of integrating biotic and abiotic methods of ANP drug degradation.
  • 1.4K
  • 26 Aug 2020
Topic Review
Anticancer Effects of Selenium Compounds
The chemistry of selenium (Se) compounds is not a young field, since its beginning was in the first half of the 19th century. The first steps in this scope were initiated in 1836 by the then toxicologists, who discovered a Se metabolite, diethyl selenide, excreted by inhalation during research using inorganic selenium compounds on animals. Meanwhile, the first synthesis of selenium-containing (Se-containing) compounds took place in 1847, when ethylselenol was obtained. Since then, selenium chemistry has developed greatly and investigators have started to look at whether it can help with society’s health problems, including cancer. The high number of new cancer incidences and the associated mortality continue to be alarming, leading to the search for new therapies that would be more effective and less burdensome for patients. As there is evidence that Se compounds can have chemopreventive activity, studies have begun to establish whether these compounds can also affect already existing cancers. This review aims to discuss the different classes of Se-containing compounds, both organic and inorganic, natural and synthetic, and the mechanisms and molecular targets of their anticancer activity.
  • 1.4K
  • 10 May 2021
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