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Topic Review
Claudin-4 as Molecular Target for Epithelial Cancer Therapy
Claudin-4 (CLDN4) is a key component of tight junctions (TJs) in epithelial cells. CLDN4 is overexpressed in many epithelial malignancies and correlates with cancer progression. Changes in CLDN4 expression have been associated with epigenetic factors (such as hypomethylation of promoter DNA), inflammation associated with infection and cytokines, and growth factor signaling. CLDN4 helps to maintain the tumor microenvironment by forming TJs and acts as a barrier to the entry of anticancer drugs into tumors. Decreased expression of CLDN4 is a potential marker of epithelial-mesenchymal transition (EMT), and decreased epithelial differentiation due to reduced CLDN4 activity is involved in EMT induction. Non-TJ CLDN4 also activates integrin beta 1 and YAP to promote proliferation, EMT, and stemness. These roles in cancer have led to investigations of molecular therapies targeting CLDN4 using anti-CLDN4 extracellular domain antibodies, gene knockdown, clostridium perfringens enterotoxin (CPE), and C-terminus domain of CPE (C-CPE), which have demonstrated the experimental efficacy of this approach. 
  • 1.1K
  • 25 May 2023
Topic Review
Neurodevelopmental Consequences of Pediatric Cancer
Cognitive impairment is frequent in pediatric cancer, and behavioral and psychological disturbances often also affect children who have survived cancer problems. Furthermore, pediatric tumors are also often associated with sleep disorders. 
  • 1.1K
  • 23 Jun 2021
Topic Review
Combined PARP inhibition Checkpoint Therapy
Genomic instability is a hallmark of cancer related to DNA damage response (DDR) deficiencies, offering vulnerabilities for targeted treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) interfere with the efficient repair of DNA damage, particularly in tumors with existing defects in DNA repair, and induce synthetic lethality. PARPi are active across a range of tumor types harboring BRCA mutations and also BRCA-negative cancers, such as ovarian, breast or prostate cancers with homologous recombination deficiencies (HRD). Depending on immune contexture, immune checkpoint inhibitors (ICIs), such as anti-PD1/PD-L1 and anti-CTLA-4, elicit potent antitumor effects and have been approved in various cancers types. Although major breakthroughs have been performed with either PARPi or ICIs alone in multiple cancers, primary or acquired resistance often leads to tumor escape. PARPi-mediated unrepaired DNA damages modulate the tumor immune microenvironment by a range of molecular and cellular mechanisms, such as increasing genomic instability, immune pathway activation, and PD-L1 expression on cancer cells, which might promote responsiveness to ICIs. In this context, PARPi and ICIs represent a rational combination.
  • 1.1K
  • 10 Oct 2020
Topic Review
Breast Cancer Bone Metastasis
Bone is one of the most common metastatic sites among breast cancer (BC) patients. Once bone metastasis is developed, patients’ survival and quality of life will be significantly declined. At present, there are limited therapeutic options for BC patients with bone metastasis. Different nanotechnology-based delivery systems have been developed aiming to specifically deliver the therapeutic agents to the bone. The conjugation of targeting agents to nanoparticles can enhance the selective delivery of various payloads to the metastatic bone lesion. 
  • 1.1K
  • 19 Apr 2022
Topic Review
Neurokinin-1 Receptor Antagonists as Therapeutic Agent for Osteosarcoma
Osteosarcoma is a bone tumor predominantly affecting children and adolescents with high malignant potential. It is a cause of serious public health challenges due to its high morbidity rates and metastatic potential. Metastasis in osteosarcoma may manifest either during treatment of the primary tumor, shortly after treatment, or a long time after the end of the treatment. So far, there are no therapeutics that can prevent or treat osteosarcoma metastasis. The peptide substance P (SP) and its high-affinity receptor, Neurokinin-1 (NK-1R), are known to positively correlate with osteosarcoma progression. Osteosarcoma cells overexpress NK-1R. SP is known to elicit the proliferation of osteosarcoma cells and induce angiogenesis and migration, leading to the invasion and metastasis of tumor cells. In contrast, NK-1R antagonists, such as aprepitant, inhibit the proliferation and induce the apoptosis of osteosarcoma cells. Aprepitant is also known to inhibit the migration of osteosarcoma cells, as well as reduce the expression levels and activities of transcriptional regulators of metastasis-related genes such as matrix metalloproteinases (MMP-2 and MMP-9), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB). These preceding studies highlighted the antimetastatic role of aprepitant in osteosarcoma Moreover, combination therapy consisting of chemotherapy and NK-1R antagonist increases the chemosensitization of osteosarcoma cells.
  • 1.1K
  • 28 Mar 2023
Topic Review
Breast Cancer in the Arabian Gulf Countries
Breast cancer stands as the prevailing malignancy across all six Gulf Cooperation Council (GCC) nations. Most of the studies reported a consistent increase in breast cancer incidence over the past decades, which was particularly attributed to the adoption of a Westernized lifestyle in the region and the implications of emerging risk factors and other environmental and societal factors, the increase in screening uptake, as well as the improvement in data collection and reporting in the GCC. The data on breast cancer risk factors in the GCC were limited. In this geographic region, breast cancer frequently manifests with distinctive characteristics, including an early onset, typically occurring before the age of 50; an advanced stage at presentation; and a higher pathological grade. 
  • 1.1K
  • 27 Nov 2023
Topic Review
Cold-Shock Domains
The cold-shock domain has a deceptively simple architecture but supports a complex biology. Cold-shock domains in human proteins are often associated with natively unfolded protein segments and more rarely with other folded domains. Human proteins containing cold-shock domains bind single-stranded DNA and/or RNA and serve a large variety of roles in regulating transcription, DNA-damage repair, RNA splicing, translation, stability and sequestration.
  • 1.1K
  • 23 Feb 2021
Topic Review
MicroRNAs in Metastasis
Metastasis is the process whereby cancer cells migrate from the primary tumour site to colonise the surrounding or distant tissue or organ. Metastasis is the primary cause of cancer-related mortality and approximately half of all cancer patients present at diagnosis with some form of metastasis. MicroRNAs (miRNAs), a class of small (19-25 nucleotides) non-coding single-strand RNAs, regulate gene expression and play an important role in cancer development and progression including in the metastatic process. 
  • 1.1K
  • 19 Jul 2021
Topic Review
EBV-Positive Mucocutaneous Ulcer
EBV-positive mucocutaneous ulcer (EBV-MCU) was classified as a rare new entity of the lymphoproliferative B-cell diseases by the WHO in 2017 and must be distinguished from head and neck squamous cell carcinoma by early biopsy.
  • 1.1K
  • 29 Apr 2022
Topic Review
Curcumin as a Chemosensitizer in Conventional Chemotherapy
Turmeric (Curcuma longa) was used for thousands of years in traditional Indian and Eastern Asian medicine. Its cultivation in the Middle East was documented since the 18th century BC in the gardens of Babylon, well before its transfer to Africa, mainly through Arabic influences. To reverse multidrug resistance, curcuminoids can be used in combination with many other drugs as chemosensitizer in cancer chemotherapy.
  • 1.1K
  • 12 Jun 2023
Topic Review
A Disintegrin and Metalloproteinase (ADAM) Family
A disintegrin and metalloproteinase (ADAM) proteins are proteolytic enzymes that are responsible for destroying the extracellular matrix, but they also have adhesive properties. Recent investigations have demonstrated that the expression of several ADAMs is upregulated in gastrointestinal (GI) tumour cells and have linked the secretion of these proteins to pathogenesis of GI malignancies.
  • 1.1K
  • 18 May 2022
Topic Review
Role of Midkine in Cancer Drug Resistance
Molecules involved in drug resistance can be targeted for better therapeutic efficacies. Research on midkine (MDK) has escalated in the last few decades, which affirms a positive correlation between disease progression and MDK expression in most cancers and indicates its association with multi-drug resistance in cancer. MDK, a secretory cytokine found in blood, can be exploited as a potent biomarker for the non-invasive detection of drug resistance expressed in various cancers and, thereby, can be targeted. 
  • 1.1K
  • 22 May 2023
Topic Review
Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma
Pancreatic cancer has a complex tumor microenvironment which engages in extensive crosstalk between cancer cells, cancer-associated fibroblasts, and immune cells. Many of these interactions contribute to tumor resistance to anti-cancer therapies. Using targeted drugs to disrupt interactions between these cells which can support cancer cell growth, invasion, and immune suppression has become an important area of exploration in the pancreatic cancer field.  Pancreatic ductal adenocarcinoma (PDAC) is the most common histology of pancreatic cancer, representing >85% of all pancreatic cancer diagnoses.
  • 1.1K
  • 08 Sep 2022
Topic Review
Nanoparticles for Thyroid Cancers
Thyroid cancer (TC) is rare relative to cancers of many other organs (breast, prostate, lung, and colon). The majority of TCs are differentiated tumors that are relatively easy to treat and have a good prognosis. However, for anaplastic TC, a rapidly growing and aggressive tumor, treatment is suboptimal because the effective drugs cause severe adverse effects. Drug delivery by nanocarriers can improve treatment by reducing side effects. This can either be mediated through better retention in the tumor tissue due to size (passive targeting) or through the attachment of specific molecules that zero in on the cancer cells (active targeting). Nanoparticles are already used for diagnosis and imaging of TC. For unresectable anaplastic TC, nanoparticle-based treatments, less suitable for deeply located cancers, could be useful, based on low-intensity focused ultrasound and near-infrared irradiation. All potential applications of nanoparticles in TC are still in the preclinical phase. 
  • 1.1K
  • 23 Aug 2021
Topic Review
Antitumor Potential of Stingless Bee Propolis and Geopropolis
Stingless bees, also known as meliponines, live in colonies and are characterized by having atrophied stingers. Propolis is a mixture of salivary secretions and plant resins collected by bees and is produced to seal the hive and prevent the entry of air and invading insects, besides having antimicrobial activity, protecting the colony from diseases. The investigation of the biological activities of stingless bee products, especially propolis and geopropolis, has revealed promising therapeutic properties, especially in the research on new antineoplastic agents.
  • 1.1K
  • 17 Nov 2021
Topic Review
Small Bowel Adenocarcinoma
Small bowel adenocarcinoma (SBA) is a rare malignancy, with a rising incidence in recent decades, and accounts for roughly 40% of all cancers of the small bowel. The majority of SBAs arise in the duodenum and are associated with a dismal prognosis. Surgery remains the mainstay of treatment for localized disease, while systemic treatments parallel those used in colorectal cancer (CRC), both in the adjuvant and palliative setting. In fact, owing to the lack of prospective data supporting its optimal management, SBA has historically been treated in the same way as CRC.
  • 1.1K
  • 23 Feb 2022
Topic Review
Selenium Deficiency and Thyroid Cancer
     Selenium (Se) is an essential micronutrient present in all tissues of the human body. It is incorporated into selenoproteins as selenocysteine (Se-Cys), the 21st amino acid. Se is present in high concentration in thyroid and plays an important role in the elimination of reactive oxygen species (ROS), and hydrogen peroxide produced during the iodination of thyroid hormones. Therefore, a fluctuation in its level could affect the expression of antioxidant selenoproteins. Indeed, Se deficiency in various diseases, including cancer, could be related to a high level of free radicals caused by oxidative stress. The relationship between Se and cancer risk is not fully understood and still debated worldwide. Most studies indicate a low Se levels in the patients with thyroid cancer.  However, some selenoproteins have been reported to fight tumor cell growth, while others support it, highlighting the fact that the role of Se in the mechanisms of thyroid tumor carcinogenesis is far from clear.
  • 1.1K
  • 30 Oct 2020
Topic Review
Allogeneic Hematopoietic Stem Cell Transplantation
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment for a variety of hematologic malignancies, immune disorders and metabolic diseases. Allo-HSCT often represents the only possible curative therapy, however it is hampered by high morbidity and mortality rates for an array of complications, including bloodstream infection and graft-versus-host disease (GvHD).
  • 1.1K
  • 22 Feb 2021
Topic Review
Metal-Based Chemotherapeutic Treatments
Herein we provides an overview of the various research approaches we have explored in recent years to improve metal-based agents for cancer or infection treatments. Although cisplatin, carboplatin, and oxaliplatin remain the cornerstones in tumor chemotherapy, the discovery and approval of novel inorganic anticancer drugs is a very slow process. Analogously, although a few promising inorganic drugs have found clinical application against parasitic or bacterial infections, their use remains relatively limited. Moreover, the discovery process is often affected by small therapeutic enhancements that are not attractive for the pharmaceutical industry. However, the availability of increasing mechanistic information for the modes of action of established inorganic drugs is fueling the exploration of various approaches for developing effective inorganic chemotherapy agents. Through a series of examples, some from our own research experience, we focus our attention on a number of promising strategies, including (1) drug repurposing, (2) the simple modification of the chemical structures of approved metal-based drugs, (3) testing novel drug combinations, and (4) newly synthesized complexes coupling different anticancer drugs. Accordingly, we aim to suggest and summarize a series of reliable approaches that are exploitable for the development of improved and innovative treatments.
  • 1.1K
  • 25 May 2021
Topic Review
Pineal Gland Tumors
Pineal gland neoplasms are tumors with different and variable morphological, histological, and radiological characteristics and, consequently different diagnosis and management. Pineal tumors, are divided into germ cell tumors, pineal parenchymal tumors and tumors that derive from adjacent structures.
  • 1.1K
  • 21 Jul 2021
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