Critical Reviews in Oncogenesis最新文献

Tumor-associated macrophages (TAMs) are the predominant cell infiltrate in the immunosuppressive tumor microenvironment (TME). TAMs are central to fostering pro-inflammatory conditions, tumor growth, metastasis, and inhibiting therapy responses. Many cancer patients are innately refractory to chemotherapy and or develop resistance following initial treatments. There is a clinical correlation between the level of TAMs in the TME and chemoresistance. Hence, the pivotal role of TAMs in contributing to chemoresistance has garnered significant attention toward targeting TAMs to reverse this resistance. A prerequisite for such an approach requires a thorough understanding of the various underlying mechanisms by which TAMs inhibit response to chemotherapeutic drugs. Such mechanisms include enhancing drug efflux, regulating drug metabolism and detoxification, supporting cancer stem cell (CSCs) resistance, promoting epithelial-mesenchymal transition (EMT), inhibiting drug penetration and its metabolism, stimulating angiogenesis, impacting inhibitory STAT3/NF-κB survival pathways, and releasing specific inhibitory cytokines including TGF-β and IL-10. Accordingly, several strategies have been developed to overcome TAM-modulated chemoresistance. These include novel therapies that aim to deplete TAMs, repolarize them toward the anti-tumor M1-like phenotype, or block recruitment of monocytes into the TME. Current results from TAM-targeted treatments have been unimpressive; however, the use of TAM-targeted therapies in combination appears promising These include targeting TAMs with radiotherapy, chemotherapy, chemokine receptor inhibitors, immunotherapy, and loaded nanoparticles. The clinical limitations of these strategies are discussed.

The current rapid development of more selective and effective drugs for the treatment of thyroid cancer has open a new era in the treatment of patients with this condition, in the past limited to the possibility of only radioactive iodine for well differentiated tumor and surgery for medullary thyroid carcinoma (MTC). The treatment of advanced medullary thyroid carcinoma has evolved in the last few years and options for patients with advanced disease are now available. Multikinase inhibitors (MKIs) with nonselective RET inhibition like Vandetanib and Cabozantinib were approved for the treatment of MTC, although the efficacy is limited due to the lack of specificity resulting in a higher rate of drug-related adverse events, leading to subsequent dose reductions, or discontinuation, and the development of a resistance mechanism like seen on the RET Val804 gatekeeper mutations. MTC is associated with mutations in the RET protooncogene, and new highly selective RET inhibitors have been developed including Selpercatinib and Pralsetinib, drugs that have demonstrate excellent results in clinical trials, and efficacy even in the presence of gatekeeper mutations. However, despite their efficacy and great tolerability, mechanisms of resistance have been described, such as the RET solvent front mutations. Due to this, the need of constant evolution and drug research is necessary to overcome the emergence of resistance mechanisms.

Deep learning (DL) is poised to redefine the way medical images are processed and analyzed. Convolutional neural networks (CNNs), a specific type of DL architecture, are exceptional for high-throughput processing, allowing for the effective extraction of relevant diagnostic patterns from large volumes of complex visual data. This technology has garnered substantial interest in the field of neuro-oncology as a promising tool to enhance medical imaging throughput and analysis. A multitude of methods harnessing MRI-based CNNs have been proposed for brain tumor segmentation, classification, and prognosis prediction. They are often applied to gliomas, the most common primary brain cancer, to classify subtypes with the goal of guiding therapy decisions. Additionally, the difficulty of repeating brain biopsies to evaluate treatment response in the setting of often confusing imaging findings provides a unique niche for CNNs to help distinguish the treatment response to gliomas. For example, glioblastoma, the most aggressive type of brain cancer, can grow due to poor treatment response, can appear to grow acutely due to treatment-related inflammation as the tumor dies (pseudo-progression), or falsely appear to be regrowing after treatment as a result of brain damage from radiation (radiation necrosis). CNNs are being applied to separate this diagnostic dilemma. This review provides a detailed synthesis of recent DL methods and applications for intratumor segmentation, glioma classification, and prognosis prediction. Furthermore, this review discusses the future direction of MRI-based CNN in the field of neuro-oncology and challenges in model interpretability, data availability, and computation efficiency.

Oral cavity cancer remains a significant cause of morbidity and mortality globally, with a poor prognosis once the disease has metastasized to cervical lymph nodes. The anatomy of lymphatic drainage in the neck gives us a roadmap to follow when assessing for metastasis, although the predictive factors are still not well understood. The mainstay of treatment continues to be neck dissection. However, there is much debate on the management of the clinically negative neck. The necessity of elective neck dissection has been questioned in recent years, with other options such as sentinel lymph node biopsy gaining popularity. This review will explore the aspects of surgical management of the neck in oral cavity cancer and highlights the further research that needs to be done.

Neuroplasticity is characterized by the brain's ability to change its activity in response to extrinsic and intrinsic factors and is thought to be the mechanism behind all brain functions. Neuroplasticity causes structural and functional changes on a molecular level, specifically the growth of different regions in the brain and changes in synaptic and post-synaptic activities. The four types of neuroplasticity are homologous area adaption, compensatory masquerade, cross-modal reassignment, and map expansion. All of these help the brain work around injuries or new information inputs. In addition to baseline physical functions, neuroplasticity is thought to be the basis of emotional and mental regulations and the impairment of it can cause various mental illnesses. Concurrently, these mental illnesses further the damage of synaptic plasticity in the brain. Major depressive disorder (MDD) is one of the most common mental illnesses. It is affected by and accelerates the impairment of neuroplasticity. It is characterized by a chronically depressed state of mind that can impact the patient's daily life, including work life and interests. This review will focus on highlighting the physiological aspects of the disease and the role of neuroplasticity in the pathogenesis and pathology of the disorder. Moreover, the role of monoamine regulation and ketamine uptake will be discussed in terms of their antidepressant effects on the outcomes of MDD.

Squamous cell carcinoma of the oral cavity presents a significant global health burden, primarily due to risk factors such as tobacco smoking, smokeless tobacco use, heavy alcohol consumption, and betel quid chewing. Common clinical manifestations of oral cavity cancer include visible lesions and sores, often accompanied by pain in advanced stages. Diagnosis relies on a comprehensive assessment involving detailed history, physical examination, and biopsy. Ancillary imaging studies and functional evaluations aid in accurate staging and facilitate treatment planning. Prognostic information is obtained from histopathological factors, such as tumor grade, depth of invasion, lymphovascular invasion, and perineural invasion. Notably, lymph node metastasis, found in approximately half of the patients, carries significant prognostic implications. Effective management necessitates a multidisciplinary approach to optimize patient outcomes. Surgical resection is the backbone of treatment, aimed at complete tumor removal while preserving functional outcomes. Adjuvant therapies, including radiation and chemotherapy, are tailored according to pathological factors. Further work in risk stratification and treatment is necessary to optimize outcomes in squamous cell carcinoma of the oral cavity.

The prevalence of electronic cigarette use has been declared an epidemic by the U.S. Surgeon General in 2018, particularly among youth aged 18-24 years old. Little is known about the differential use of e-cigarettes by different groups. PubMed, Cochrane, and Google Scholar were used to find relevant articles. A total of 77 articles were included. The extant literature reveals disparities in e-cigarette use by race/ethnicity and sexuality/gender. There are conflicting conclusions regarding disparities by socioeconomic status.