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Topic Review
Immunotherapy for Glioblastoma
       Glioblastoma (GBM) is the deadliest and most aggressive neuroepithelial cancer of the central nervous system (CNS) with an abysmal median survival of 14.6-month despite the multiple forms of intervention. In the United States, the total annual incidence rate of glioma has been ~6 cases per 100,000 individuals, of which GBM accounts for about 50% of the cases, with a higher predominance in males. Clinical studies have indicated that most of the GBM patients present an intact blood–brain barrier (BBB) for certain brain regions, capable of blocking the delivery of agents to cancer sites. The BBB is considered to prevent diffusion of 98% of small-molecule and 100% of large-molecule agents into the brain from blood circulation. Given the aggressive and heterogeneous nature of GBM and the blocking capability of BBB, a very limited number of medications for patients with GBM is available in clinics. In addition, due to the existence of other cellular and extracellular barriers, as well as the development of drug resistance over the treatment course, the efficacy of many current therapeutic approaches has been compromised.        Currently available standards of care for GBM include maximal tumor resection followed by radiotherapy, chemotherapy, and corticosteroids, all of which have immune suppressive characteristics. Unfortunately, complete surgical removal of the whole tumor is almost impossible due to their diffusive characteristics into normal brain tissue. Some reports indicated that ~65% of the post-surgery cases still showed residual tumor cells, which eventually contributed to a high relapse rate of GBM . Therefore, GBM patients may undergo repeated surgical resection, radiotherapy, chemotherapy, or additional bevacizumab treatment. Eventually, most of the patients suffering from GBM will relapse despite an ample set of interventional approaches. According to the data from Surveillance and Epidemiology, the median overall survival (OS) of GBM patients was normally less than 2 years from the time of first progression or relapse. An international phase III randomized trial, conducted by the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada (EORTC/NCIC), has shown that the median OS of GBM patients who received radiotherapy and Temozolomide therapy remains poor (14.6 months). Moreover, Grossman and colleagues found that the utilization of systemic chemotherapy and hyperfractionated radiation therapy with corticosteroids is likely to disable immune activity. Immune-suppressive characteristics, high toxicity, and lower OS of traditional care made a considerable number of GBM patients (~50%) not accept any second-line of anti-tumor treatment. In addition, there is no evidence that traditional intervention can significantly impact the OS rate under a recurrence setting. Accordingly, given the poor prognosis and limited therapy regimens for patients affected by GBM, there is an urgent need to develop novel therapeutic approaches.
  • 1.1K
  • 25 Aug 2020
Topic Review
Therapy-Related MN and Clonal Hematopoiesis
In the last decades the improved management of cancer patients and the overall prolonged life expectancy contributed to the increased number of patients at risk of late clonal events such as therapy-related myeloid neoplasms (t-MN). The discovery of clonal hematopoiesis of indeterminate potential (CHIP) in normal individuals has shed light on the pathophysiologic mechanism behind the process of myeloid evolution, defining CHIP carriers at higher risk of progression. Moreover, different patterns of clonal evolution have been identified in case of t-MN development after anti-cancer treatment exposure. 
  • 1.1K
  • 22 Apr 2021
Topic Review
Bone in Inherited Endocrine Tumors
Endocrine tumors are neoplasms originating from specialized hormone-secreting cells. They can develop as sporadic tumors, caused by somatic mutations, or in the context of familial Mendelian inherited diseases. Congenital forms, manifesting as syndromic or non-syndromic diseases, are caused by germinal heterozygote autosomal dominant mutations in oncogenes or tumor suppressor genes.
  • 1.1K
  • 30 Aug 2021
Topic Review
Necroptosis and Prostate Cancer
Necroptosis is a programmed form of necrosis characterized by mitochondrial alterations and plasma membrane permeabilization resulting in the release of cytoplasmic content into extracellular space, and leading to inflammatory reactions. Besides its critical role in viral defense mechanisms and inflammatory diseases, necroptosis plays pivotal functions in the drug response of tumors, including prostate cancer. Necroptosis is mainly governed by kinase enzymes, including RIP1, RIP3, and MLKL, and conversely to apoptosis, is a caspase-independent mechanism of cell death. Numerous compounds induce necroptosis in prostate cancer models, including (i) compounds of natural origin, (ii) synthetic and semisynthetic small molecules, and (iii) selenium and selenium-based nanoparticles.
  • 1.1K
  • 13 Apr 2022
Topic Review
IDH Mutations in Chondrosarcoma
Chondrosarcomas are malignant cartilage-producing tumours that frequently harbour isocitrate dehydrogenase 1 and -2 (IDH) gene mutations. Several studies have confirmed that these mutations are key players in the early stages of cartilage tumour development, but their role in later stages remains ambiguous. The prognostic value of the IDH mutation in chondrosarcoma seems controversial and (pre)clinical studies that have focused on the direct and indirect targeting of the IDH mutation have not yielded novel treatment strategies.
  • 1.1K
  • 21 Aug 2023
Topic Review
Drug Development Platform for Cholangiocarcinoma
Cholangiocarcinoma (CCA), a group of malignancies that originate from the biliary tract, is associated with a high mortality rate and a concerning increase in worldwide incidence. In Thailand, where the incidence of CCA is the highest, the socioeconomic burden is severe. Yet, treatment options are limited, with surgical resection being the only form of treatment with curative intent. The current standard-of-care remains to be adjuvant and palliative chemotherapy which is ineffective in most patients. The overall survival rate is dismal, even after surgical resection and the tumor heterogeneity further complicates treatment. Together, this makes CCA a significant burden in Southeast Asia. For effective management of CCA, treatment must be tailored to each patient, individually, for which an assortment of targeted therapies must be available
  • 1.1K
  • 09 Feb 2021
Topic Review
ADGRG1/GPR56 in Tumor Progression
Cellular communication plays a critical role in diverse aspects of tumorigenesis including tumor cell growth/death, adhesion/detachment, migration/invasion, angiogenesis, and metastasis. G protein-coupled receptors (GPCRs) which constitute the largest group of cell surface receptors are known to play fundamental roles in all these processes. When considering the importance of GPCRs in tumorigenesis, the adhesion GPCRs (aGPCRs) are unique due to their hybrid structural organization of a long extracellular cell-adhesive domain and a seven-transmembrane signaling domain. Indeed, aGPCRs have been increasingly shown to be associated with tumor development by participating in tumor cell interaction and signaling. ADGRG1/GPR56, a representative tumor-associated aGPCR, is recognized as a potential biomarker/prognostic factor of specific cancer types with both tumor-suppressive and tumor-promoting functions. 
  • 1.1K
  • 16 Dec 2021
Topic Review
PARP Inhibitors in Cancer Immunotherapy
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxic effects as single agents in tumors characterized by defective repair of DNA double-strand breaks deriving from BRCA1/2 mutations or other abnormalities in genes associated with homologous recombination. Preclinical studies have shown that PARPi-induced DNA damage may affect the tumor immune microenvironment and immune-mediated anti-tumor response through several mechanisms. In particular, increased DNA damage has been shown to induce the activation of type I interferon pathway and up-regulation of PD-L1 expression in cancer cells, which can both enhance sensitivity to Immune Checkpoint Inhibitors (ICIs).
  • 1.1K
  • 30 Nov 2022
Topic Review
Angiocrine Factors Control Tumor Progression
A solid tumor mass consists not only of cancer cells, but of numerous other resident and infiltrating cells and the extracellular matrix, which together form the tumor microenvironment (TME). The TME contains three main cell entities: fibroblasts, immune cells and endothelial cells. Endothelial cells control their microenvironment through the expression of membrane-bound and secreted factors. Such angiocrine functions are frequently hijacked by cancer cells, which deregulate the signaling pathways controlling the expression of angiocrine factors.
  • 1.1K
  • 23 Jun 2021
Topic Review
Immune Checkpoint Inhibitors in Urothelial Bladder Cancer
Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette–Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease.
  • 1.1K
  • 19 Jun 2023
Topic Review
Non-Coding RNAs in Glioblastoma
Non-coding RNAs have been implicated as master regulators of several biological processes, their expression being strictly regulated under physiological conditions. In recent years, particularly in the last decade, substantial effort has been made to investigate the function of ncRNAs in several human diseases, including cancer. The aim of this review is to guide the reader through important aspects of miRNA and lncRNA biology, focusing on the molecular mechanism associated with glioblastoma onset/progression.
  • 1.1K
  • 28 Oct 2020
Topic Review
ICIs for HCC treatment
Immunotherapies are promising approaches for treating hepatocellular carcinomas (HCCs) refractory to conventional therapies. However, a recent clinical trial of immune checkpoint inhibitors (ICIs) revealed that anti-tumor responses to ICIs are not satisfactory in HCC cases. Therefore, it is critical to identify molecular markers to predict outcome and develop novel combination therapies that enhance the efficacy of ICIs. Recently, several attempts have been made to classify HCC based on genome, epigenome, and transcriptome analyses. These molecular classifications are characterized by unique clinical and histological features of HCC, as well immune phenotype. For example, HCCs exhibiting gene expression patterns with proliferation signals and stem cell markers are associated with the enrichment of immune infiltrates in tumors, suggesting immune-proficient characteristics for this type of HCC. However, the presence of activating mutations in β-catenin represents a lack of immune infiltrates and refractoriness to ICIs. Although the precise mechanism that links the immunological phenotype with molecular features remains controversial, it is conceivable that alterations of oncogenic cellular signaling in cancer may lead to the expression of immune-regulatory molecules and result in the acquisition of specific immunological microenvironments for each case of HCC. Therefore, these molecular and immune characteristics should be considered for the management of HCC using immunotherapy.
  • 1.1K
  • 02 Nov 2020
Topic Review
Irreversible Electroporation (IRE)
Electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. 
  • 1.1K
  • 07 May 2021
Topic Review
Golden Syrian Hamster Models for Cancer Research
The golden Syrian hamster (Mesocricetus auratus) has long been a valuable rodent model of human diseases, especially infectious and metabolic diseases. Hamsters have also been valuable models of several chemically induced cancers such as the DMBA-induced oral cheek pouch cancer model.
  • 1.1K
  • 19 Aug 2022
Topic Review
Exosomes Diversity
Cells can communicate through special “messages in the bottle”, which are recorded in the bloodstream inside vesicles, namely exosomes. The exosomes are nanovesicles of 30–100 nm in diameter that carry functionally active biological material, such as proteins, messanger RNA (mRNAs), and micro RNA (miRNAs). Therefore, they are able to transfer specific signals from a parental cell of origin to the surrounding cells in the microenvironment and to distant organs through the circulatory and lymphatic stream. More and more interest is rising for the pathological role of exosomes produced by cancer cells and for their potential use in tumor monitoring and patient follow up. In particular, the exosomes could be an appropriate index of proliferation and cancer cell communication for monitoring the minimal residual disease, which cannot be easily detectable by common diagnostic and monitoring techniques. The lack of unequivocal markers for tumor-derived exosomes calls for new strategies for exosomes profile characterization aimed at the adoption of exosomes as an official tumor biomarker for tumor progression monitoring.
  • 1.1K
  • 21 Nov 2020
Topic Review
Hypoxia
Hypoxia is a condition commonly observed in the core of solid tumors. The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. These events favor tumor progression and chemoresistance. The increase in glucose and amino acid uptake, glycolytic flux, and lactate production; the alterations in glutamine metabolism, tricarboxylic acid cycle, and oxidative phosphorylation; the high levels of mitochondrial reactive oxygen species; the modulation of both fatty acid synthesis and oxidation are hallmarks of the metabolic rewiring induced by hypoxia.
  • 1.1K
  • 18 Dec 2020
Topic Review
Structure Dynamics and Signaling of the Neurokinin-1 Receptor
Substance P (SP), the first isolated neuropeptide, belongs to the family of tachykinin peptides and is the natural ligand of neurokinin-1 receptors (NK-1R), also named SP receptors. The undecapeptide activates the receptor after specifically binding to the protein and triggers intracellular signals leading to different biochemical events and subsequent physiological responses. 
  • 1.1K
  • 21 Oct 2022
Topic Review
Clinical Applications of Short Non-Coding RNA-Based Therapies
RNA therapies have demonstrated clinical potential for both the treatment of cancer and other pathologies. Therapeutic delivery and resulting adverse events remain significant roadblocks in implementing many of these drugs into clinical practice, but the FDA approval of three Alnylam Pharmaceuticals’ small interfering RNAs (siRNAs) therapies has been a milestone in developing therapies tailored to disease-driving target genes. While it seems that RNAs can be administered “naked” in closed-compartment organs such as eyes and lungs, more research is needed for systemic administration. Lipid nanoparticles represent a promising delivery method, but some challenges remain because of their potential to elicit an immune response, relatively low circulation times, and relatively large size. The use of GalNAc for the delivery and targeting of siRNAs has made significant progress, but delivery systems targeted to organs other than the liver would broaden the range of diseases that could be treated with RNA therapies.
  • 1.1K
  • 07 Apr 2022
Topic Review
Locoregional Therapies in Patients with Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most commonly diagnosed primary liver malignancy. Its efficient management depends on early detection, the stage of progression of the disease and underlying liver function. Available curative treatments include liver transplantation, resection and ablation. These are in addition to cryoablation, microwave ablation and percutaneous alcohol injection. In cases of the late detection of HCC, many patients with locally advanced disease and are offered locoregional therapies, including transarterial chemoembolization and selective internal radiation therapy, plus external beam radiation.
  • 1.1K
  • 28 Mar 2023
Topic Review
HER2 Status in the Biliary Tract Cancers
Biliary tract cancer (BTC) is traditionally known as being hard to treat with a poor prognosis. State-of-the-art genomic technologies such as next-generation sequencing (NGS) revolutionized cancer management and shed light on the genomic landscape of BTCs. There are ongoing clinical trials to assess the efficacy of HER2-blocking antibodies or drug conjugates in BTCs with HER2 amplifications. 
  • 1.1K
  • 10 May 2023
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