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Topic Review
Wnt/β-Catenin Target Genes
The Wnt/β-catenin cell–cell signaling pathway is one of the most basic and highly conserved pathways for intercellular communications regulating key steps during development, differentiation, and cancer. In colorectal cancer (CRC), in particular, aberrant activation of the Wnt/β-catenin pathway is believed to be responsible for perpetuating the disease from the very early stages of cancer development. A large number of downstream target genes of β-catenin-T-cell factor (TCF), including oncogenes, were detected as regulators of CRC development.
  • 475
  • 08 Apr 2021
Topic Review
Wnt/β-Catenin Signaling in Liver Cancers
Liver cancer is among the leading global healthcare issues associated with high morbidity and mortality. Liver cancer consists of hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), hepatoblastoma (HB), and several other rare tumors. Progression has been witnessed in understanding the interactions between etiological as well as environmental factors and the host in the development of liver cancers. However, the pathogenesis remains poorly understood, hampering the design of rational strategies aiding in preventing liver cancers. Accumulating evidence demonstrates that aberrant activation of the Wnt/β-catenin signaling pathway plays an important role in the initiation and progression of HCC, CCA, and HB. Targeting Wnt/β-catenin signaling potentiates a novel avenue for liver cancer treatment, which may benefit from the development of numerous small-molecule inhibitors and biologic agents in this field.
  • 394
  • 29 Sep 2021
Topic Review
WNT Signalling in Dental Pathologies
Great efforts have been made over the past decades to discover new therapeutic targets for a big variety of human pathologies. Most of the studies dealing with severe pathological conditions such as cancers and tissue malformations are focused on the role of either widely recognized master controlling genes such as ras and myc or pivotal components of key signalling pathways, among which Wnt and Notch. However, these genes and molecules are fundamental for paired embryogenesis as well as for tissue and organ homeostasis and regeneration, where they regulate cell proliferation, migration, differentiation and apoptosis. The precise timing and localization of their activation are important to ensure the appropriate cellular functions in physiological conditions. Thus, their indiscriminate targeting is not desirable, due to both the high risk of severe side effects and the certainty of broad phenotypic consequences. On the contrary, optimal therapeutic targets should be selected based on their tissue, time and pathology specific roles. Here, we suggest a paradigmatic example of such target molecules that could be represented by the Wnt/b-catenin signalling components Bcl9 and Bcl9l. 
  • 988
  • 05 Nov 2020
Topic Review
Wnt Signaling in Keratinocyte Carcinomas
The skin functions as a barrier between the organism and the surrounding environment. Direct exposure to external stimuli and the accumulation of genetic mutations may lead to abnormal cell growth, irreversible tissue damage and potentially favor skin malignancy. Skin homeostasis is coordinated by an intricate signaling network, and its dysregulation has been implicated in the development of skin cancers. Wnt signaling is one such regulatory pathway orchestrating skin development, homeostasis, and stem cell activation. Aberrant regulation of Wnt signaling cascades not only gives rise to tumor initiation, progression and invasion, but also maintains cancer stem cells which contribute to tumor recurrence.
  • 497
  • 22 Sep 2021
Topic Review
Wnt Signaling in Human Diseases
Wnt signaling has been implicated in a wide spectrum of important biological phenomena, where either a deficiency or overactivation of key effectors can lead to various human diseases. This review highlights historical and recent findings on key mediators of Wnt signaling and its association with various developmental diseases and tumorigenesis.
  • 792
  • 13 Nov 2020
Topic Review
Wnt Pathway: A Tailored Target
Cancer represents one of the greatest public health challenges. One of the most cancer-driving events embodies the dysregulation of both the canonical and the non-canonical Wnt/β-catenin pathway. The impact of the Wnt/β-catenin pathway has been widely reviewed in colorectal, breast, and ovarian cancers.  Genetic and epigenetic alterations are commonly detected in colorectal cancers (CRCs). As a matter of fact, 70% of CRCs are connoted by the APC mutations and almost all patients display an overactive Wnt/β-catenin pathway also mediated by oncogenic miRNAs. Therefore, miRNAs have been proposed as anti-cancer and/or diagnostic/prognostic tools. Among cancers, breast cancer (BC) is one of the most expensive health care costs with a high rate of diagnosis and deaths per year. The Wnt/β-catenin cascade and in particular the β-catenin content has been correlated with a dismal prognosis, high tumour grade, and metastasis formation. In addition in triple-negative breast cancer (TNBC) both the canonical and the non-canonical Wnt/β-catenin pathways have been reported as drivers of cancer dissemination, aggressiveness, early age of onset, and poor outcome. To add further complexity, the Wnt5a ligand was found to display both anti-tumour and tumour promoting properties depending on the tumour microenvironment (TME), the activation of specific signalling pathways, and the receptor availability in BC.  Likewise, an abnormal Wnt/β-catenin cascade has been shown to strongly contribute to ovarian cancer (OC) growth, stemness, and drug resistance.  In the last decades, particular attention has been dedicated to investigate the role of extracellular vesicles (EVs) released in the TME in cancer growth and progression. EVs are heterogeneous small membrane-bound carriers with a complex cargo contributing to cell-to-cell communication, tumour growth, invasion, and chemoresistance. Since EVs can be detected in the majority of biological fluids and in the TME, EVs have been proposed as diagnostic and/or prognostic tools, as well as useful therapeutic options. Indeed, EVs engineered with specific anti-tumour molecules or loaded with conventional anti-tumour drugs have been proposed as novel anti-cancer options. Based on these notions, in the last decades, Wnt/β catenin targeting approaches have been explored to hinder tumour expansion. However so far, the most relevant limitation relies on the crucial role played by the Wnt/β catenin cascade in tissue homeostasis. Therefore, to develop targeting approaches the identification of the specific EV cargo driving tumour progression and the mechanisms accounting for the unbalanced Wnt/β catenin pathway in cancer should be considered as the most challenging issues.
  • 557
  • 03 Nov 2020
Topic Review
Wild-type IDH Enzymes
Isocitrate dehydrogenases (IDHs) are enzymes that catalyze the oxidative decarboxylation of isocitrate, producing α-ketoglutarate (αKG) and CO2. The discovery of IDH mutations in several malignancies has led to a better characterization of IDHs involvement in tumorigenesis and the approval of drugs targeting IDH1/2 mutants in cancers. Nevertheless, less is known about the impact of IDH mutants in rare pathologies or the relevance of non-mutated IDH enzymes in cancers. Here, we provide a brief overview of the impact of IDHs enzymes as potential therapeutic targets.  
  • 1.3K
  • 30 Oct 2020
Topic Review
Whole Brain Radiotherapy among Lung Cancer Patients
Lung cancer is the most common cancer causing brain metastases at the time of diagnosis and brain metastases can be found in up to 50% of patients with lung cancer. Brain metastases among lung cancer patients have, in general, been associated with serious symptoms and a short survival. However, local treatments of brain metastases have been developed over time in terms of refined neuroimaging, surgery, and radiotherapy. This allows patients to receive improved treatment with prolonged benefits and fewer side effects. In addition, there have been advances in systemic oncological therapies for lung cancer patients in recent years, and systemic treatment, including chemotherapy, targeted therapy, and immunotherapy, may prevent or delay brain metastases. Determining the appropriate treatment for patients with lung cancer and brain metastases, therefore, requires a clear understanding of the brain metastases, molecular characteristics, tumor histology, and the overall lung cancer prognosis.
  • 239
  • 12 Apr 2022
Topic Review
Well-Differentiated Thyroid Cancer
Well-differentiated thyroid carcinoma (WDTC) is a slow-growing cancer with a good prognosis, but may show extraglandular progression involving the invasion of tumor-adjacent tissues, such as the trachea, esophagus, and recurrent laryngeal nerve. Tracheal invasion by WDTC is infrequent. Since this condition is rare, relevant high-level evidence about it is lacking. Tracheal invasion by a WDTC has a negative impact on survival, with intraluminal tumor development constituting a worse prognostic factor than superficial tracheal invasion. In WDTC, curative resection is often feasible with a small safety margin, and complete resection can ensure a good prognosis. Despite its resectability, accurate knowledge of the tracheal and peritracheal anatomy and proper selection of surgical techniques are essential for complete resection. However, there is no standard guideline on surgical indications and the recommended procedure in trachea-invading WDTC. This review discusses the indications for radical resection and the three currently available major resection methods: shaving, window resection, and sleeve resection with end-to-end anastomosis.
  • 392
  • 02 Mar 2021
Topic Review
Web Axillary Pain Syndrome: Novel Rehabilitative Suggestions
Axillary web syndrome (AWS) is defined as a visible and palpable network of cords in the skin of the axillary cavity that are tensed by shoulder abduction following surgery for breast cancer, causing significant functional limits of the ipsilateral upper limb (UL) and pain. The purpose of this narrative review is to discuss rehabilitation approaches for greater efficacy with respect to pain and novel suggestions. AWS is a frequent complication of axillary lymphadenectomy that necessitates a thorough follow-up in the medium to long term. Physiotherapy is effective in the treatment of functional limb deficits, the management of pain, and the treatment of upper limb disability. The best management approach involves the use of soft tissue techniques to slow the natural course of the syndrome, in association with therapeutic exercises for functional recovery and muscle strengthening. AWS is linked secondary lymphedema, requiring integration with manual lymphatic drainage. The physiotherapy management of AWS is currently fragmented, and insufficient information is available on the nature of the disease. Thus, randomized and controlled studies that compare rehabilitation approaches in AWS are desirable, including the possibility of using mesotherapy in the treatment of axillary and upper limb pain
  • 354
  • 05 Nov 2021
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