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Topic Review
Resectable IIIA-N2 NSCLC
Locally advanced non-small cell lung cancer accounts for one third of non-small cell lung cancer (NSCLC) at the time of initial diagnosis and presents with a wide range of clinical and pathological heterogeneity. To date, the combined multimodality approach involving both local and systemic control is the gold standard for these patients, since occult distant micrometastatic disease should always be suspected. With the rapid increase in treatment options, the need for an interdisciplinary discussion involving oncologists, surgeons, radiation oncologists and radiologists has become essential. Surgery should be recommended to patients with non-bulky, discrete, or single-level N2 involvement and be included in the multimodality treatment. Resectable stage IIIA patients have been the subject of a number of clinical trials and retrospective analysis, discussing the efficiency and survival benefits on patients treated with the available therapeutic approaches. However, most of them have some limitations due to their retrospective nature, lack of exact pretreatment staging, and the involvement of heterogeneous populations leading to the awareness that each patient should undergo a tailored therapy in light of the nature of his tumor, its extension and his performance statu
  • 839
  • 04 Aug 2020
Topic Review
Key Heterocyclic Anti-Angiogenic Leads
Pathological angiogenesis is a hallmark of cancer; accordingly, a number of anticancer FDA-approved drugs act by inhibiting angiogenesis via different mechanisms. However, the development process of the most potent anti-angiogenics has met various hurdles including redundancy, multiplicity, and development of compensatory mechanisms by which blood vessels are remodeled. Moreover, identification of broad-spectrum anti-angiogenesis targets is proved to be required to enhance the efficacy of the anti-angiogenesis drugs. In this perspective, a proper understanding of the structure activity relationship (SAR) of the recent anti-angiogenics is required. Various anti-angiogenic classes have been developed over the years; among them, the heterocyclic organic compounds come to the fore as the most promising, with several drugs approved by the FDA.
  • 839
  • 24 Feb 2021
Topic Review
Non-Metastatic Castration-Resistant Prostate Cancer
Non-metastatic castration-resistant prostate cancer (nmCRPC) is defined by a progressively rising prostate-specific antigen level, despite a castrate level of testosterone, in the absence of obvious radiologic evidence of metastatic disease on conventional imaging modalities. As a significant proportion of patients with nmCRPC develop metastatic diseases, the therapeutic goals of physicians for these patients are to delay metastasis development, preserve quality of life, and increase overall survival (OS). Since 2018, the treatment of nmCRPC has changed dramatically with the introduction of second-generation androgen receptor inhibitors, such as enzalutamide (ENZA), apalutamide (APA), and darolutamide (DARO).
  • 839
  • 23 Jun 2021
Topic Review
H3K18Ac as a Biomarker in Cancer Progression
Acetylation and deacetylation are posttranslational modifications (PTMs) which affect the regulation of chromatin structure and its remodeling. Acetylation of histone 3 at lysine placed on position 18 (H3K18Ac) plays an important role in driving progression of many types of cancer, including breast, colon, lung, hepatocellular, pancreatic, prostate, and thyroid cancer. 
  • 839
  • 27 Apr 2022
Topic Review
Targeting Cell Surface GRP78 in Cancer
The 78-kDa glucose-regulated protein (GRP78) is an endoplasmic reticulum (ER)-resident molecular chaperone that plays a crucial role in protein folding homeostasis by regulating the unfolded protein response (UPR). In tumour cells, GRP78 is present at the cell surface, where it functions as a signalling receptor involved in numerous proapoptotic and apoptotic pathways that contribute to cancer cell proliferation and metastasis. As such, novel therapeutic strategies that target cell surface GRP78 in the treatment of several human cancers is highlighted.
  • 839
  • 01 Jul 2022
Topic Review
Different Phenotypes of Immune Infiltrates
Besides the mere count of lymphocytic infiltration, the phenotype of the lymphocytes may also dictate the clinical outcome of HER2-positive breast cancer patients, as every specific subset has a specific role in cancer development. Cumulative data from human studies have associated the different immune populations with a predominant contribution to either pro- or antitumor activities.
  • 839
  • 17 Jan 2023
Topic Review
The Sarcoma Immune
Sarcomas are a rare disease with high rates of recurrence and poor prognosis. Available therapeutic options for advanced disease are limited and based on chemotherapeutic regimens. Immuno-oncological compounds have shown effectivity in different cancer indications, and their benefit is also expected in sarcomas. The role of the tumor microenvironment in sarcoma, prognosis, and response to novel immunotherapies are summarized here.
  • 838
  • 19 Feb 2021
Topic Review
Antidiabetic Medications and Cancer
In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed. Antidiabetic medications can modulate cancer risk through directly impacting metabolism of cancer cells as well as indirectly through impact on risk factors of malignancy. Some of them are considered beneficial (metformin and thiazolidinedions—with the exception of bladder cancer); on the other hand, excess of exogenous insulin may be potentially harmful, while other medications seem to have neutral impact on cancer risk. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) are increasingly used in the treatment of type 2 diabetes. However, their association with cancer risk is unclear. 
  • 838
  • 22 Sep 2021
Topic Review
Lung Cancer Diagnosis
Lung cancer is the leading cause of cancer-related deaths in North America and other developed countries. One of the reasons lung cancer is at the top of the list is that it is often not diagnosed until the cancer is at an advanced stage. Thus, the earliest diagnosis of lung cancer is crucial, especially in screening high-risk populations, such as smokers, exposure to fumes, oil fields, toxic occupational places, etc. Based on the current knowledge, it looks that there is an urgent need to identify novel biomarkers. The current diagnosis of lung cancer includes different types of imaging complemented with pathological assessment of biopsies, but these techniques can still not detect early lung cancer developments.
  • 838
  • 13 Sep 2021
Topic Review
Palliative Sedation
Palliative sedation can be considered as “the last resort” in order to treat unbearable, refractory symptoms or suffering in end-of-life patients. 
  • 838
  • 08 Mar 2022
Topic Review
Therapeutic Potential of PI3K/AKT/mTOR Pathway
Gastrointestinal stromal tumor (GIST) originates from interstitial cells of Cajal (ICCs) in the myenteric plexus of the gastrointestinal tract. Most GISTs arise due to mutations of KIT and PDGFRA gene activation, encoding the receptor tyrosine kinase (RTK). The clinical use of the RTK inhibitor imatinib has significantly improved the management of GIST patients; however, imatinib resistance remains a challenge. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a critical survival pathway for cell proliferation, apoptosis, autophagy and translation in neoplasms. Constitutive autophosphorylation of RTKs has an impact on the activation of the PI3K/AKT/mTOR pathway. In several preclinical and early-stage clinical trials PI3K/AKT/mTOR signaling inhibition has been considered as a promising targeted therapy strategy for GISTs. Various inhibitory drugs targeting different parts of the PI3K/AKT/mTOR pathway are currently being investigated in phase I and phase II clinical trials. This review highlights the progress for PI3K/AKT/mTOR-dependent mechanisms in GISTs, and explores the relationship between mTOR downstream signals, in particular, eukaryotic initiation factors (eIFs) and the development of GISTs, which may be instrumental for identifying novel therapeutic targets.
  • 837
  • 03 Nov 2020
Topic Review
TRIM Proteins
The TRIpartite Motifs (TRIM) protein family is composed of more than 70 known TRIM proteins in humans and mice, which are encoded by approximately 71 genes in humans.
  • 837
  • 07 Apr 2021
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.
  • 837
  • 08 Apr 2021
Topic Review
Efficacy of Auto-CAR T Cell Therapy in Lymphoma
While more than half of non-Hodgkin lymphomas (NHL) can be cured with modern frontline chemoimmunotherapy regimens, outcomes of relapsed and/or refractory (r/r) disease in subsequent lines remain poor, particularly if considered ineligible for hematopoietic stem cell transplantation. Hence, r/r NHLs represent a population with a high unmet medical need. This therapeutic gap has been partially filled by adoptive immunotherapy. CD19-directed autologous chimeric antigen receptor (auto-CAR) T cells have been transformative in the treatment of patients with r/r B cell malignancies.
  • 837
  • 19 Aug 2022
Topic Review
Tumour Blood Vessels
Tumour blood vessels, characterised by abnormal morphology and function, create an immunosuppressive tumour microenvironment via restricting the appropriate leucocyte subsets trafficking. Strategies to trigger phenotypic alteration in tumour vascular system to resemble normal vascular system, named vascular normalisation, promote effective trafficking of leucocytes into tumours through enhancing the interactions between leucocytes and endothelial cells. 
  • 836
  • 28 Apr 2021
Topic Review
Phytonutrients in Curing Breast Cancer
Breast cancer (BC) is one of the most common causes of female mortality around the globe. It is the second most common cancer and the fifth leading cause of death from cancer in the world. It accounts for around 25% of all female cancers. The worldwide incidence of BC in 2012 was 1.67 million, which is alarming. The incidence may increase to 3.2 million by 2050. Males may also develop BC, but this is very rare, accounting for <1% of diagnosed BCs worldwide. BC may be of different types, based on various factors including etiology, location, and clinical and molecular characteristics. Based on location, BC may be of two types; namely, non-invasive and invasive. Non-invasive BC does not extend away from the lobules or duct where it is located. Invasive BC, on the other hand, reaches out from the lobules and ducts to the nearby mammary tissue.
  • 836
  • 18 Aug 2021
Topic Review
Pre-Clinical Research on MPM Biology
Malignant pleural mesothelioma (MPM) is an aggressive cancer of the lung lining that is associated with asbestos exposure. Due to a lack of effective biomarkers coupled with a long latency period from asbestos exposure to cancer development, prognosis of MPM is poor with an average survival of 8–14 months following diagnosis. Pre-clinical investigations aimed to develop novel biomarkers and treatment strategies are urgently needed to improve MPM diagnosis and treatments available to MPM patients. Novel protein and microRNA biomarkers constitute promising diagnostic biomarkers of MPM; and treatment strategies such as targeted-, immune- and viro-therapy exhibit promising efficacy.
  • 836
  • 12 Oct 2021
Topic Review
Salinomycin and Its Bioactivity
Cancer stem cells (CSCs) are the cells in a primary tumor that have the opportunity to self-renew as well as differentiate into certain cell types, thus forming a mixed tumor. CSCs have been shown to be involved in every aspect of cancer development, including tumor initiation, proliferation, and metastatic activity; they are also involved in chemotherapeutic drug resistance and the recurrence of certain cancers. Based on these capabilities, CSCs have been explored as the next target for the treatment and management of cancer. Salinomycin (SAL), a polyether ionophore antibiotic being used in the poultry industry, was identified as a powerful anti-cancer compound that possesses broad-spectrum activities, especially against CSCs. 
  • 836
  • 12 May 2023
Topic Review
Bispecific Antibodies in Lung Cancer
Lung cancer is the leading cause of cancer-related death worldwide according to the World Health Organization. Non-small cell lung cancer makes up the majority of cases. Immunotherapy with immune checkpoint inhibitors and targeted therapy with tyrosine kinase inhibitors and other molecular targeted agents significantly changed the treatment landscape and overall survival. Unfortunately, resistance to these treatments develops, and there is a need to identify additional innovative therapies that can overcome treatment resistance. Advancements in biomedical engineering and technology allowed for the development of novel agents, capable of delivering effective treatment directly to tumor cells. These agents include antibody drug conjugates and bispecific antibodies which have various targets and mechanisms of action.
  • 836
  • 21 Jun 2023
Topic Review
Hypoxia inducible factor in nephrotoxicity
Cisplatin is a highly effective, broad-spectrum chemotherapeutic drug, yet its clinical use and efficacy are limited by its side effects. Particularly, cancer patients receiving cisplatin chemotherapy have high incidence of kidney problems. Hypoxia-inducible factor (HIF) is the “master” transcription factor that is induced under hypoxia to trans-activate various genes for adaptation to the low oxygen condition. Numerous studies have reported that HIF activation protects against AKI and promotes kidney recovery in experimental models of cisplatin-induced acute kidney injury (AKI). In contrast, little is known about the effects of HIF on chronic kidney problems following cisplatin chemotherapy. Prolyl hydroxylase (PHD) inhibitors are potent HIF inducers that recently entered clinical use. By inducing HIF, PHD inhibitors may protect kidneys during cisplatin chemotherapy. However, HIF activation by PHD inhibitors may reduce the anti-cancer effect of cisplatin in tumors.
  • 835
  • 26 Jan 2021
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