Epidemiological data demonstrate that patients with diabetes have an augmented risk of developing various types of cancers, accompanied by higher mortality. A number of mechanisms for this connection have been hypothesized, such as insulin resistance, hyperinsulinemia, hyperglycemia, and increased inflammatory processes. Apart from these potential mechanisms, several diabetes-associated dysregulated cytokines might be implicated in the link between diabetes and cancer. In fact, some inflammatory cytokines, e.g. TNF-α, IL-6 and leptin, have been revealed to play important roles in both initiation and progression of tumor. Here, we depict the role of these cytokines in key events of carcinogenesis and cancer development, including their capability to induce oxidative stress, inflammation, their participation in epithelial mesenchymal transition (EMT), angiogenesis, and metastasis. Finally, we will also highlight the existing knowledge in terms of the involvement of these cytokines in different cancer types and comment on potential significances for future clinical applications.

Ovarian cancer (OC) is a serious condition that often presents at advanced stages and has high mortality rates, with the current mode of early-stage screening lacking sensitivity and specificity. OC often presents asymptomatically, which renders early diagnosis difficult. Furthermore, many patients lack significant risk factors or family history of the disease. Five-year survival rates differ between patients with OC among racial, ethnic, and social groups as a result of different social barriers. This review article aims to present the currently existing data regarding health care disparities among OC patients of different ethnic, demographic, and socioeconomic backgrounds, and what next steps should be taken to better understand and eventually eliminate these potentially devastating health care disparities. Increasing data support the notion that a combination of genomic, socioeconomic status, social factors, and cultural differences lead to differential treatments and therefore health care disparities. While genomic and biological factors are important, language barriers, geographic and travel barriers, differences in comorbidity likelihood between populations, and different treatment plans seem to have a greater impact on 5-year survival rates of patients from diverse backgrounds. Language barriers limit a shared-decision model of care. Transportation limitations and geographic differences can lead to limited follow-up and insufficient care in resource and equipment restrictive settings. Patients with these barriers also tend to have a higher incidence of comorbidities that raise the mortality rate of OC. Further research needs to explore effective solutions to bridge health care disparities and understand why they occur.

A growing body of literature supports the role of apolipoproteins present in HDL in the treatment of pro-inflammatory diseases including cancer. We examined whether bovine HDL (bHDL) and three dual-domain peptides, namely AEM-28 and its analog AEM-28-2, and HM-10/10, affect tumor growth and development in mouse models of ovarian and colon cancer. We demonstrate that bHDL inhibits mouse colorectal cancer cell line CT26-mediated lung tumor development, and mouse ovarian cancer cell line ID8-mediated tumor burden. We also demonstrate that, although to different degrees, dual-domain peptides inhibit cell viability of mouse and human ovarian and colon cancer cell lines, but not that of normal human colonic epithelial cells or NIH3T3 mouse fibroblasts. Dual-domain peptides administered subcutaneously or in a chow diet decrease CT26 cell-mediated tumor burden, tumor growth, and tumor dissemination in BALB/c mice. Plasma levels of lysophosphatidic acid (LPA) are significantly reduced in mice that received bHDL and the dual-domain peptides, suggesting that reduction by effecting accumulation and/or synthesis of pro-inflammatory lipids may be one of the mechanisms for the inhibition of tumor development by bHDL and the dual-domain peptides. Our studies suggest that therapeutics based on apolipoproteins present in HDL may be novel agents for the treatment of epithelial adenocarcinomas of the ovary and colon.

A greater understanding of factors causing cancer initiation, progression and evolution is of paramount importance. Among them, the serine/threonine phosphatase PPM1D, also referred to as wild-type p53-induced phosphatase 1 (Wip1) or protein phosphatase 2C delta (PP2Cδ), is emerging as an important oncoprotein due to its negative regulation on a number of crucial cancer suppressor pathways. Initially identified as a p53-regulated gene, PPM1D has been afterwards found amplified and more recently mutated in many human cancers such as breast cancer. The latest progress in this field further reveals that selective inhibition of PPM1D to delay tumor onset or reduce tumor burden represents a promising anti-cancer strategy. Here, we review the advances in the studies of the PPM1D activity and its relevance to various cancers, and recent progress in development of PPM1D inhibitors and discuss their potential application in cancer therapy. Consecutive research on PPM1D and its relationship with cancer is essential, as it ultimately contributes to the etiology and treatment of cancer.

The abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.

Background

Endometriosis is complex, but identifying the novel biomarkers, inflammatory molecules, and genetic links holds the key to the enhanced detection, prediction and treatment of both endometriosis and endometriosis related malignant neoplasia. Here we review the literature relating to the specific molecular mechanism(s) mediating tumorigenesis arising within endometriosis.

Methods

Guidance (e.g. Cochrane) and published studies were identified. The Published studies were identified through PubMed using the systematic review methods filter, and the authors' topic knowledge. These data were reviewed to identify key and relevant articles to create a comprehensive review article to explore the molecular fingerprint associated with in endometriosis-driven tumorigenesis.

Results

An important focus is the link between C3aR1, PGR, ER1, SOX-17 and other relevant gene expression profiles and endometriosis-driven tumorigenesis. Further studies should also focus on the combined use of CA-125 with HE-4, and the role for OVA1/MIA as clinically relevant diagnostic biomarkers in the prediction of endometriosis-driven tumorigenesis.

Conclusions

Elucidating endometriosis' molecular fingerprint is to understand the molecular mechanisms that drive the endometriosis-associated malignant phenotype. A better understanding of the predictive roles of these genes and the value of the biomarker proteins will allow for the derivation of unique molecular treatment algorithms to better serve our patients.