Critical Reviews in Oncogenesis最新文献

Breast cancer (BC) is the most common malignancy among women, with over one million cases occurring annually worldwide. Although therapies against estrogen receptors and HER2 have improved response rate and survival, patients with advanced disease, who are resistant to anti-hormonal therapy and/or to chemotherapy, have limited treatment options for reducing morbidity and mortality. These limitations provide major incentives for developing new, effective, and personalized therapeutic interventions. This review presents evidence on the involvement of dopamine (DA) and its type 1 receptors (D1R) in BC. DA is produced in multiple peripheral organs and is present in the systemic circulation in significant amounts. D1R is overexpressed in ~ 30% of BC cases and is associated with advanced disease and shortened patient survival. Activation of D1R, which signals via the cGMP/PKG pathway, results in apoptosis, inhibition of cell invasion, and increased chemosensitivity in multiple BC cell lines. Fenoldopam, a peripheral D1R agonist that does not penetrate the brain, dramatically suppressed tumor growth in mouse models with D1R-expressing BC xenografts. It is proposed that D1R should serve as a novel diagnostic/prognostic factor through the use of currently available D1R detection methods. Fenoldopam, which is FDA-approved to treat renal hypertension, could be repurposed as an effective therapeutic agent for patients with D1R-expressing tumors. Several drugs that interfere with the cGMP/PKG pathway and are approved for treating other diseases should also be considered as potential treatments for BC.

Oral cancer is a heterogeneous, aggressive, and complex entity. Current major treatment options for the disease are surgery, chemo, and/or radiotherapy either alone or in combination with each other. Each treatment method has its own limitations such as a significant journey with deformities and a protracted rehabilitation process leading to loss of self-esteem, loss of tolerance, and therapeutic side effects. Conventional therapies are frequently experienced with regimen resistance and recurrence attributed to the cancer stem cells (CSCs). Given that CSCs exert their tumorigenesis by affecting several cellular and molecular targets and pathways an improved understanding of CSCs' actions is required. Hence, more research is recommended to fully understand the fundamental mechanisms driving CSC-mediated treatment resistance. Despite the difficulties and disagreements surrounding the removal of CSCs from solid tumors, a great amount of knowledge has been derived from the characterization of CSCs. Various efforts have been made to identify the CSCs using several cell surface markers. In the current review, we will discuss numerous cell surface markers such as CD44, ALDH1, EPCAM, CD24, CD133, CD271, CD90, and Cripto-1 for identifying and isolating CSCs from primary oral squamous cell carcinoma (OSCC). Further, a spectrum of embryonic signaling pathways has been thought to be the main culprit of CSCs' active state in cancers, resulting in conventional therapeutic resistance. Hence, we discuss the functional and molecular bases of several signaling pathways such as the Wnt/beta;-catenin, Notch, Hedgehog, and Hippo pathways and their associations with disease aggressiveness. Moreover, numerous inhibitors targeting the above mentioned signaling pathways have already been identified and some of them are already undergoing clinical trials. Hence, the present review encapsulates the characterization and effectiveness of the prospective potential targeted therapies for eradicating CSCs in oral cancers.

Hepatocellular carcinoma (HC) is a malignant primary liver cancer which has poor treatment outcomes in advanced stages, and many of the HC patients present with advanced stages. The incidence of death due to HC increase as a result of ineffective treatments for advanced stage disease. Early diagnosis and management has proven benefits in both survival and quality of life. Currently very few biomarkers are available to provide diagnostic and prognostic benefits in HC patients. The present review elaborates the association of cardiac markers in HC disease. The HC disease pathology includes many cardiovascular events like hypoxia and other parameters discussed in this review which have a role in disease advancement, and also may help as diagnostic and / or prognostic markers. The scientific lacuna in association / role of cardiac markers in HC disease is also stated in this review which may be helpful for future research studies and develop cost effective biomarker for early diagnosis of HC.

Liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, can be devastating if not treated early. The risk factors of liver cancer include alcoholic liver disease, non-alcoholic fatty liver disease, disruption of melatonin levels, and dysregulated circadian rhythm. The circadian rhythm is a 24-hour biological clock that regulates the physiological activities at both central and peripheral levels. Its molecular mechanism exists in every cell in mammals. Disruption of the circadian rhythm has found in liver cancers as an independent risk factor. This review summarized the most recent findings about the molecular mechanisms of circadian rhythm, the crosstalk between core clock genes and melatonin, as well as the role of circadian rhythm and melatonin played in chronic liver diseases and liver cancer. Finally, we discussed the potential clinical application of circadian rhythm and melatonin for the treatment of liver cancer and discussed future perspectives of how understanding the circadian rhythm in liver cancer progression could provide new clinical applications for liver cancer treatment and diagnosis.

Nonalcoholic fatty liver disease (NAFLD) is a pathological condition, wherein fat deposition exceeds the allowable limits of the healthy person. If the condition persists for a long time, the patient will eventually develop NASH (nonalcoholic steatohepatitis), which will probably lead to HCC (hepatocellular carcinoma). The incidence of NAFLD is rising at an alarming rate, and still there are no drugs approved by the U.S. Food and Drug Administration for this devastating health condition. To combat and treat NAFLD successfully, it is essential to understand how routine lipid metabolism in the liver is altered under these conditions. In this review, we discuss specifically during the NAFLD progression how the signaling pathways leading to excess fat accumulation in the liver are changed. We also address variations in the mechanisms underlying hepatic lipid uptake and changes in fatty acid oxidation mechanisms. We will also highlight the role of transcription factors and other lipolytic enzymes that stringently regulate the hepatic de novo lipolysis (DNL) and emphasize how they are altered during NAFLD progression. Finally, we will also touch upon how the lipid disposal from the liver goes wrong during the NAFLD progression. A comprehensive understanding of the changes in lipid metabolism is essential for developing successful therapies for NAFLD.

Liver cancer (LC) is the most common high-mortality malignancy, due to its aggressive nature, heterogeneity, and metastasis. Recent studies have recognized long noncoding RNAs (lncRNAs) as mediators of LC pathogenesis and metastasis. This review describes the role of lncRNAs in molecular mechanisms of tumorigenicity, metastasis, stem-cell maintenance, drug resistance, and tumor immunity. We present recent updates on therapeutic targeting of lncRNAs in LC as well as lncRNA's potential for LC diagnosis. Overall, we provide a new perspective on the role of lncRNAs for LC treatment and diagnosis.