Critical Reviews in Oncogenesis最新文献

Liver cancer is classified amongst the foremost causes of tumor-associated deaths around the world. The liver cancer death is more common in men compared to females with overall death rate being doubled from 1980-2017. A primary pathological category of liver cancer is the hepatocellular carcinoma (HCC), which accounts for nearly 80% of all liver cancers. Since HCC is mainly diagnosed at advanced stages, making the surgical and locoregional treatments extremely difficult. Dysregulation of transcription factors, the central modulators of normal and transformed tumorous cellular processes such as STAT-1, STAT-3, NF-κB, Ap1, and HIF-1α are known to be activated in HCC invasion, progression, and metastasis are highlighted in this review. The recently approved drugs, such as sorafenib regorafenib, lenvatinib, and cabozantinib, are tyrosine kinase inhibitors (TKIs), which completely reduce HCC progression by targeting transcription factors are discussed.

The expansion of metal-based complexes in the last 20 years has been very intense and many metals have been involved. Among the many compounds studied, the ruthenium-based complex NAMI-A embodies the unique paradigm of the ability to selectively inhibiting and preventing the development and the growth of distant metastases originating from solid tumors in all the tumor models on which it has been tested. An activity that can be detected only in vivo since the compound is virtually free of measurable direct cell cytotoxicity in vitro. Recently, a published paper reported on a significant in vitro cytotoxicity against some leukemic cells. The present study was undertaken to reproduce those experiments to further support this novel antileukemic activity that would have put NAMI-A on a new trajectory for development. Our results do not confirm the efficacy of NAMI-A in vitro against the human HL-60 promyelocytic leukemia cell line either using test cultures identical to those reported in the study of reference or in even more stressed conditions, supporting the lack of in vitro direct cell cytotoxicity of NAMI-A. The present study also helps to elucidate that many factors can influence the outcome of in vitro tests of cytotoxicity and suggests caution to speculate on possible therapeutic properties based on the results of simple and reductive in vitro tests of cytotoxicity.

Current statistics related to cancer incidence and cancer-related death rates clearly show that specific racial/ethnic minorities are more likely to be diagnosed and/or die with cancer. Colorectal cancer (CRC) is one of the leading causes of cancer deaths in the United States and it disproportionately affects the non-Hispanic Black or African American (AA) population. When compared to the non-Hispanic White (nHW) population, incidence and death rates in AAs are 28% and 60% higher, respectively. Hispanics have an overall lower CRC incidence rate than nHWs (Hispanics: 35.5 per 100,000 population; nHWs: 40.2 per 100,000 population), but their incidence continues to rise, unlike nHWs, who are experiencing a decline. This disparity between Hispanics and nHWs is further highlighted in the younger Hispanic population. While the cause of the disparities is associated with CRC-related genetic and environmental factors, the role of specific genes/mutations in each population are still not fully unraveled. However, because CRC is a slowly progressing disease, routine screening and/or early intervention are key to achieving better outcomes in CRC patients and ultimately in closing the disparity gap among different populations. This review discusses the major factors influencing the disparities in CRC and also focuses on factors such as treatment response, family history, and screening that potentially contribute to the racial/ethnic disparities in CRC.

Liver cancer is the 6th leading cause of cancer related deaths in the US even though it ranks 14th in incidence. More men are diagnosed with liver cancer than women, and the number of projected deaths among men (20,020) is almost double that among women (10,140) in the US. Infections like hepatitis and metabolic conditions like obesity are believed to be major risk factors for the onset of liver cancer. Hepatocellular carcinoma (HCC), the most common type of liver cancer, accounts for 75% of all cases. Chemotherapy has not been effective in treating HCC. Targeted therapies are being used in advanced HCC patients due to a better survival and less side effects when compared to traditional chemotherapy. Therapeutic agents targeting the regulators of growth factor signaling pathways and the mediators of downstream signaling-for example, inhibitors of the tyrosine kinase receptor-are used as targeted molecular therapies. Kinase inhibitors that modulate growth signals, such as sorafenib and lenvatinib, are commonly employed in targeted molecular therapy for HCC patients. This review covers these agents, highlighting modes of action and providing details on clinical trials.

Small intestinal bacterial overgrowth (SIBO) is a common gastrointestinal (GI) problem, but its diagnosis is often missed in the clinical setting. Because its diagnosis mostly requires invasive testing, often its true prevalence is unknown. Commonly presenting complaints include abdominal distension, diarrhea, and malabsorption. Multiple predisposing factors have been recognized in peer-reviewed literature, including achlorhydria, motility disorders, anatomical abnormalities of the gastrointestinal tract, and immunodeficiency disorders, including cancer. Multiple culture-dependent and independent methods are used to confirm diagnosis. Symptomatic relief can be achieved through multiple antibiotics regimens, but correction of underlying etiology, if possible, is necessary for long-lasting cure. Increased awareness and clinical vigilance can transform the landscape of SIBO via better management of patients with GI and related disorders.

The major challenging problem in the world is cancer. It is a complex disease. Somatic mutations in the genome cause genetic changes and lead to initiation and promotion of tumor growth. Many researchers are working to identify cancer driver mutations using traditional approaches. In combination with traditional approaches, computational approaches provide a new insight for novel therapeutic options in oncology. In order to address this problem, there is a need to implement computational approaches like genomics, proteomics, and metabolomics to overcome the problem with less time for accurate results. This review discusses one computational method: genome-wide association studies for identifying SNPs in colon, gastrointestinal, esophageal, and pancreatic cancers.

Human epidermal growth factor receptor 2 (HER2) oncogene addiction has led to the development of anti-HER2 therapies which have revolutionized the management of patients with HER2-positive cancers, with trastuzumab being the cornerstone of treatment of HER2-positive breast cancer. Despite the success of these biologics in breast cancer patients, not all patients with HER2-positive tumors respond to treatment, and many eventually develop resistance to therapy. Developing therapies that that circumvent current resistance mechanisms and improve patient outcomes further remains an area of unmet clinical need. Based on insights gained from established anti-HER2 therapies and our understanding of known resistance mechanisms a number of novel anti-HER2 treatments are being developed. These include novel HER2 antibody-drug conjugates that have shown activity in HER2 high and low tumors, novel HER2 antibodies, T cell bispecific antibodies, and HER2 antibodies in combination with phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitors, immunotherapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. In this article, we review resistance mechanisms to approved HER2 antibodies and provide an overview of emerging therapeutic agents.