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Topic Review
Brain Cancer Chemotherapy Using Monoclonal Antibody Conjugates
Central nervous system (CNS) drug delivery into the brain across the endothelium is difficult due to the blood-brain barrier (BBB), which is composed mainly of tight junctions and efflux transporters, such as multiple drug resistance 1 (MDR1) (P-glycoprotein). On the other hand, the development of anti-cancer drugs is a challenging task due to their frequent off-target side effects and the complicated mechanisms of cancer pathogenesis and progression. Brain cancer treatment options are surgery, radiation therapy, and chemotherapy. It is difficult to remove all tumor cells, even by surgical removal after a craniotomy. Accordingly, innovative brain cancer drugs are needed. Currently, antibody (Ab) drugs that show high therapeutic effects are often used clinically. Furthermore, antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan, an anti-HER2 (human epidermal receptor 2) ADC with low-molecular cancer drugs through the suitable linker, have been developed. In the case of trastuzumab deruxtecan, it is internalized into cancer cells across the membrane via receptor-mediated endocytosis. Moreover, it is reported that drug delivery into the brain across the BBB was carried out via receptor-mediated transcytosis (RMT), using anti-receptor Abs as a vector against the transferrin receptor (TfR) or insulin receptor (InsR). Thus, anti-TfR ADCs with cancer drugs are promising brain cancer agents due to their precise distribution and low side effects.
  • 1.3K
  • 20 Jul 2022
Topic Review
miRNAs in HTLV-1 Induced T Cell Leukemia
Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. 
  • 1.3K
  • 23 May 2022
Topic Review
Chromatin Dysregulation of Prostate Cancer
The dysregulation of chromatin and epigenetics has been defined as the overarching cancer hallmark. By disrupting transcriptional regulation in normal cells and mediating tumor progression by promoting cancer cell plasticity, this process has the ability to mediate all defined hallmarks of cancer.
  • 1.3K
  • 13 Jul 2021
Topic Review
Blastic Plasmacytoid Dendritic Cell Neoplasm
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare tumour, which usually affects elderly males and presents in the skin with frequent involvement of the bone-marrow, peripheral blood and lymph nodes. It has a dismal prognosis, with most patients dying within one year when treated by conventional chemotherapies. The diagnosis is challenging, since neoplastic cells can resemble lymphoblasts or small immunoblasts, and require the use of a large panel of antibodies, including those against CD4, CD56, CD123, CD303, TCL1, and TCF4. The morphologic and in part phenotypic ambiguity explains the uncertainties as to the histogenesis of the neoplasm that led to the use of various denominations. 
  • 1.3K
  • 28 Sep 2021
Topic Review
Lynch-like Syndrome
Lynch-like syndrome (LLS) is defined as colorectal cancer cases with microsatellite instability (MSI) and loss of expression of MLH1, MSH2, MSH6, or PMS2 by immunohistochemistry (IHC) in the absence of a germline mutation in these genes that cannot be explained by BRAF mutation or MLH1 hypermethylation.
  • 1.3K
  • 11 Mar 2022
Topic Review
Veterinary Antiparasitic to Human Anticancer
Cancer is an extensive disease and the most common cause of morbidity and mortality worldwide. It is characterized by a deregulation of the cell cycle, which primarily results in a progressive loss of control of cellular growth and differentiation. The repurposing of veterinary antiparasitic drugs for the treatment of cancer is gaining traction, as supported by existing literature. A prominent example is the proposal to implement the use of veterinary antiparasitics such as benzimidazole carbamates and halogenated salicylanilides as novel anticancer drugs. These agents have revealed pronounced anti-tumor activities and gained special attention for “double repositioning”, as they are repurposed for different species and diseases simultaneously, acting via different mechanisms depending on their target. As anticancer agents, these compounds employ several mechanisms, including the inhibition of oncogenic signal transduction pathways of mitochondrial respiration and the inhibition of cellular stress responses.
  • 1.3K
  • 29 Apr 2022
Topic Review
Vincristine (VCR)
Vincristine (VCR) is a frequently used chemotherapeutic agent. However, it can lead to VCR-induced peripheral neuropathy (VIPN). 
  • 1.3K
  • 24 Dec 2020
Topic Review
Heat Shock Protein 70 Inhibitors
A class of chaperones dubbed heat shock protein 70 (Hsp70) possesses high relevance in cancer diseases due to its cooperative activity with the well-established anticancer target Hsp90. However, Hsp70 is closely connected with a smaller heat shock protein, Hsp40, forming a formidable Hsp70-Hsp40 axis in various cancers, which serves as a suitable target for anticancer drug design. 
  • 1.3K
  • 27 Feb 2023
Topic Review
Microbiota-Derived Approach in PDAC Treatment
Most cancer treatment modalities efficient in other malignancies display limited efficacy in pancreatic cancer, and novel therapeutic strategies in a multidisciplinary approach are highly warranted.
  • 1.3K
  • 05 Jan 2022
Topic Review
Pediatric Mixed-Phenotype Acute Leukemia
Mixed phenotypic acute leukemias (MPAL) are rare hematological malignancies in children, accounting for less than 5% of pediatric acute leukemias. MPAL are heterogeneous and can exhibit cross-lineage myeloid, B-lymphoid, or T-lymphoid antigen expression on a single blast population (biphenotypic) or have distinct single-lineage blast populations (bilineal). Due to phenotypic and genetic diversity, lack of well-defined diagnostic criteria, treatment resistance, and lineage switch, MPAL often present a diagnostic dilemma, and prove difficult to treat.
  • 1.3K
  • 30 Nov 2021
Topic Review
Pancreatic ductal adenocarcinoma (PDAC)
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer-related mortality. About 90% of PDAC cases are diagnosed in patients older than 55 years, and with increased longevity in the general population PDAC burden is expected to rise. Still, the survival is abysmal, with a 5-year survival rate of 8.2%.
  • 1.3K
  • 02 Aug 2021
Topic Review
ROS in Cancer Cell Metabolism
Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts.
  • 1.3K
  • 22 Sep 2021
Topic Review
IL-6 Signaling in colorectal cancer onset and progression
IL-6 is a pleiotropic cytokine showing both pro- and anti-inflammatory roles.
  • 1.3K
  • 10 Dec 2021
Topic Review
Connexins in Cancer
The expression, localization, and function of connexins, the protein subunits that comprise gap junctions, are often altered in cancer. In addition to cell–cell coupling through gap junction channels, connexins also form hemichannels that allow communication between the cell and the extracellular space and perform non-junctional intracellular activities. Historically, connexins have been considered tumor suppressors; however, they can also serve tumor-promoting functions in some contexts. Here, we review the literature surrounding connexins in cancer cells in terms of specific connexin functions and propose that connexins function upstream of most, if not all, of the hallmarks of cancer. The development of advanced connexin targeting approaches remains an opportunity for the field to further interrogate the role of connexins in cancer phenotypes, particularly through the use of in vivo models. More specific modulators of connexin function will both help elucidate the functions of connexins in cancer and advance connexin-specific therapies in the clinic.
  • 1.3K
  • 24 Dec 2020
Topic Review
Targeting Epigenetic Modifications in UM
Uveal melanoma (UM), the most common intraocular malignancy in adults, is a rare subset of melanoma. Despite effective primary therapy, around 50% of patients will develop the metastatic disease. Several clinical trials have been evaluated for patients with advanced UM, though outcomes remain dismal due to the lack of efficient therapies. Epigenetic dysregulation consisting of aberrant DNA methylation, histone modifications, and small non-coding RNA expression, silencing tumor suppressor genes, or activating oncogenes, have been shown to play a significant role in UM initiation and progression. Given that there is no evidence any approach improves results so far, adopting combination therapies, incorporating a new generation of epigenetic drugs targeting these alterations, may pave the way for novel promising therapeutic options. Furthermore, the fusion of effector enzymes with nuclease-deficient Cas9 (dCas9) in clustered regularly interspaced short palindromic repeats (CRISPR) associated protein 9 (Cas9) system equips a potent tool for locus-specific erasure or establishment of DNA methylation as well as histone modifications and, therefore, transcriptional regulation of specific genes.
  • 1.3K
  • 10 Aug 2020
Topic Review
HOX Proteins
Invasion and metastasis correspond to the foremost cause of cancer-related death, and the molecular networks behind these two processes are extremely complex and dependent on the intra- and extracellular conditions along with the prime of the premetastatic niche. Currently, several studies suggest an association between the levels of HOX genes expression and cancer cell invasion and metastasis, which favour the formation of novel tumour masses. The deregulation of HOX genes by HMGA2/TET1 signalling and TGFβ pathway, the HOX interference in EMT (Epithelial to Mesenchymal Transition) process and the regulatory effect of noncoding RNAs (miRs and lncRNAs) generated by the HOX loci can also promote invasion and metastasis, interfering with the expression of HOX genes or other genes relevant to these processes.
  • 1.3K
  • 20 Jan 2021
Topic Review
Head and Neck Squamous Carcinomas
Head and neck squamous cell carcinomas (HNSCC) are among the most common and lethal tumors worldwide, occurring mostly in oral cavity, pharynx, and larynx tissues. The squamous epithelia homeostasis is supported by the extracellular matrix (ECM), and alterations in this compartment are crucial for cancer development and progression. Laminin is a fundamental component of ECM, where it represents one of the main components of basement membrane (BM), and data supporting its contribution to HNSCC genesis and progression has been vastly explored in oral cavity squamous cell carcinoma. Laminin subtypes 111 (LN-111) and 332 (LN-332) are the main isoforms associated with malignant transformation, contributing to proliferation, adhesion, migration, invasion, and metastasis, due to its involvement in the regulation of several pathways associated with HNSCC carcinogenesis, including the activation of the EGFR/MAPK signaling pathway. Therefore, it draws attention to the possibility that laminin may represent a convergence point in HNSCC natural history, and an attractive potential therapeutic target for these tumors. 
  • 1.3K
  • 25 May 2021
Topic Review
Ozone as a Chemotherapy
In the last sixty years, publications in reputed journals have shown the preclinical positive effect of ozone gas in cancer cells. However, the translation of these results into clinical practice is far away from success. A comprehensive approach is necessary for this, and oncologists and researchers need guidance from medical specialists with in-depth knowledge of ozone in medicine. In this article, we review the evidence around this question and suggest different potential research lines to those interested in this exciting field.
  • 1.3K
  • 23 Nov 2021
Topic Review
Diagnosis and Prognosis of HGSOC
High-grade serous ovarian carcinoma (HGSOC) represents the most common form of epithelial ovarian carcinoma. The absence of specific symptoms leads to late-stage diagnosis, making HGSOC one of the gynecological cancers with the worst prognosis. The cellular origin of HGSOC, the role of reproductive hormones, the genetic and chromosomal traits, or the pathways mainly involved in the physiopathology of this cancer, as well as when evaluating prognosis and response to therapy in  patients. Despite the growing knowledge on this field, the detection of HGSOC is still based on traditional methods such as carbohydrate antigen 125 (CA125) detection and ultrasound, and the combined use of these methods has yet to support significant reductions in overall mortality rates, which opens new avenues to guide research towards the early diagnosis of HGSOC.
  • 1.3K
  • 30 Nov 2022
Topic Review
Immunotherapy Challenges in Multiple Myeloma
The power of immunotherapy in the battle of Multiple Myeloma (MM) started with allogeneic stem cell transplantation, and was rediscovered with immunomodulatory drugs and extended with the outstanding results achieved with targeted antibodies. Today, next to powerful antibodies Elotuzumab and Daratumumab, several T-cell-based immunotherapeutic approaches, such as bispecific antibodies and chimeric antigen receptor-transduced T-cells (CAR T-cells) are making their successful entry in the immunotherapy arena with highly promising results in clinical trials. Nonetheless, similar to what is observed in chemotherapy, MM appears capable to escape from immunotherapy, especially through tight interactions with the cells of the bone marrow microenvironment (BM-ME). This review will outline our current understanding on how BM-ME protects MM-cells from immunotherapy through immunosuppression and through induction of intrinsic resistance against cytotoxic effector mechanisms of T- and NK-cells.
  • 1.3K
  • 18 Dec 2020
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