Oncogenesis 

About: Oncogenesis is an academic journal published by Nature Portfolio. The journal publishes majorly in the area(s): Medicine & Biology. It has an ISSN identifier of 2157-9024. It is also open access. Over the lifetime, 99 publications have been published receiving 257 citations. The journal is also known as: Oncogenesis.

Exosomes and cancer - Diagnostic and prognostic biomarkers and therapeutic vehicle

Abstract: Exosomes belong to a subpopulation of extracellular vesicles secreted by the dynamic multistep endocytosis process and carry diverse functional molecular cargoes, including proteins, lipids, nucleic acids (DNA, messenger and noncoding RNA), and metabolites to promote intercellular communication. Proteins and noncoding RNA are among the most abundant contents in exosomes; they have biological functions and are selectively packaged into exosomes. Exosomes derived from tumor, stromal and immune cells contribute to the multiple stages of cancer progression as well as resistance to therapy. In this review, we will discuss the biogenesis of exosomes and their roles in cancer development. Since specific contents within exosomes originate from their cells of origin, this property allows exosomes to function as valuable biomarkers. We will also discuss the potential use of exosomes as diagnostic and prognostic biomarkers or predictors for different therapeutic strategies for multiple cancers. Furthermore, the applications of exosomes as direct therapeutic targets or engineered vehicles for drugs are an important field of exosome study. Better understanding of exosome biology may pave the way to promising exosome-based clinical applications.

Breast cancer in the era of integrating “Omics” approaches

Abstract: Worldwide, breast cancer is the leading cause of cancer-related deaths in women. Breast cancer is a heterogeneous disease characterized by different clinical outcomes in terms of pathological features, response to therapies, and long-term patient survival. Thus, the heterogeneity found in this cancer led to the concept that breast cancer is not a single disease, being very heterogeneous both at the molecular and clinical level, and rather represents a group of distinct neoplastic diseases of the breast and its cells. Indubitably, in the past decades we witnessed a significant development of innovative therapeutic approaches, including targeted and immunotherapies, leading to impressive results in terms of increased survival for breast cancer patients. However, these multimodal treatments fail to prevent recurrence and metastasis. Therefore, it is urgent to improve our understanding of breast tumor and metastasis biology. Over the past few years, high-throughput "omics" technologies through the identification of novel biomarkers and molecular profiling have shown their great potential in generating new insights in the study of breast cancer, also improving diagnosis, prognosis and prediction of response to treatment. In this review, we discuss how the implementation of "omics" strategies and their integration may lead to a better comprehension of the mechanisms underlying breast cancer. In particular, with the aim to investigate the correlation between different "omics" datasets and to define the new important key pathway and upstream regulators in breast cancer, we applied a new integrative meta-analysis method to combine the results obtained from genomics, proteomics and metabolomics approaches in different revised studies.

Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy

Abstract: Abstract Neutrophils are central mediators of innate and adaptive immunity and first responders to tissue damage. Although vital to our health, their activation, function, and resolution are critical to preventing chronic inflammation that may contribute to carcinogenesis. Cancers are associated with the expansion of the neutrophil compartment with an escalation in the number of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in the peripheral circulation and tumor microenvironment. Although phenotypically similar to classically activated neutrophils, PMN-MDSC is pathologically activated and immunosuppressive in nature. They dynamically interact with other cell populations and tissue components and convey resistance to anticancer therapies while accelerating disease progression and metastatic spread. Cancer-associated neutrophilia and tumor infiltration of neutrophils are significant markers of poor outcomes in many cancers. Recently, there has been significant progress in the identification of molecular markers of PMN-MDSC providing insights into the central role of PMN-MDSC in the local tumor microenvironment as well as the systemic immune response in cancer. Further advances in sequencing and proteomics techniques will improve our understanding of their diverse functionalities and the complex molecular mechanisms at play. Targeting PMN-MDSC is currently one of the major focus areas in cancer research and several signaling pathways representing possible treatment targets have been identified. Positive results from preclinical studies clearly justify the current investigation in drug development and thus novel therapeutic strategies are being evaluated in clinical trials. In this review, we discuss the involvement of PMN-MDSC in cancer initiation and progression and their potential as therapeutic targets and clinical biomarkers in different cancers.

Lipids in cancer: a global view of the contribution of lipid pathways to metastatic formation and treatment resistance

Abstract: Lipids are essential constituents for malignant tumors, as they are absolutely required for tumor growth and dissemination. Provided by the tumor microenvironment (TME) or by cancer cells themselves through activation of de novo synthesis pathways, they orchestrate a large variety of pro-tumorigenic functions. Importantly, TME cells, especially immune cells, cancer-associated fibroblasts (CAFs) and cancer-associated adipocytes (CAAs), are also prone to changes in their lipid content, which hinder or promote tumor aggressiveness. In this review, we address the significant findings for lipid contribution in tumor progression towards a metastatic disease and in the poor response to therapeutic treatments. We also highlight the benefits of targeting lipid pathways in preclinical models to slow down metastasis development and overcome chemo-and immunotherapy resistance.

PSMC2 promotes the progression of gastric cancer via induction of RPS15A/mTOR pathway

Abstract: As one of the most common malignant tumors, it is particularly important to further understand the development mechanism of gastric cancer and to find more effective therapeutic target genes. The results of immunohistochemical staining showed that PSMC2 was upregulated in gastric cancer. Cell function experiments indicated that PSMC2 knockdown inhibited the proliferation, clone formation and migration of gastric cancer cells, and induced apoptosis. In vivo experiments further showed that PSMC2 knockdown suppressed tumor growth. RPS15A and mTOR pathway were identified the downstream gene and pathway of PSMC2 by GeneChip and IPA. PSMC2 knockdown inhibited RPS15A expression and mTOR pathway, which was neutralized by RPS15A overexpression. Overexpression of RPS15A promoted the proliferation and migration of gastric cancer cells, which alleviated the inhibitory effect caused by PSMC2 knockdown to a certain extent. The mTOR pathway inhibitor Torin1 partially restored the promoting role of RPS15A overexpression on the gastric cancer cell proliferation. Furthermore, bioinformatics analysis and dual-luciferase reporter assays showed that PSMC2 and RPS15A competitively bound to hsa-let-7c-3p. Inhibition of hsa-let-7c-3p promoted the migration of MGC-803 cells and reduced the apoptosis level, while simultaneous inhibition PSMC2 and hsa-let-7c-3p restored the migration and apoptosis levels of gastric cancer cells. In conclusion, PSMC2 and RPS15A were highly expressed in gastric cancer. PSMC2 enhanced RPS15A levels by targeting hsa-let-7c-3p, and then activated mTOR pathway, thereby promoting the progression of gastric cancer.