The Wnt/β‐catenin pathway is an important, dysregulated pathway in several tumor types, including pancreatic ductal adenocarcinoma. Although the activation of this pathway is an important component of normal development, its aberrant activation resulting from activating or inactivating mutations in the CTNNB1 gene locus, or in the negative regulators AXIN and APC involving stabilization of β‐catenin, and activation of target genes leads to a more aggressive phenotype, suggesting its potential value as a therapeutic target in the treatment of pancreatic ductal adenocarcinoma. A number of small molecule and biologic agents have now been developed for targeting this pathway. This review summarizes the current knowledge about the therapeutic potential of targeting the Wnt pathway with particular emphasis on preclinical/clinical studies in the treatment of pancreatic ductal adenocarcinoma.

Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF‐308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®‐probes‐based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval [CI]: 1.57‐4.83, <0.001) and OR of 7.27 (95%CI: 2.5‐20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF‐308 G>A located on TNF‐a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.

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Angiogenesis refers to the formation of recent blood vessels, which is one of the characteristics of cancer progression and it has been deliberated as a putative target to the treatment of many kinds of cancers. The VEGF signaling substrate is very important for angiogenesis and is commonly high-regulated in tumors. As a result, this molecule has attracted the attention of most of the researchers to develop antiangiogenic therapies. We have presented that VEGF blockage in neoadjuvant setting via bevacizumab, aflibercept and sunitinib not only has revealed some promising benefits but also has shown a large negative outcome in the adjuvant trials. However, at an advanced stage of tumors, suppression of VEGF alone is inadequate to stop advancement, encouraging drug resistance, and probably enhancing metastasis and invasion in the tumor microenvironment, thereby suggesting the therapeutic potential of targeting angiogenic pathways in gastrointestinal cancers.

Toll‐like receptors (TLRs) play an important role in the innate and adaptive immune system. They are expressed in various regions of the female reproductive tract, and their regulation may be involved in the pathogenesis of gynecological lesions. There is growing evidence that ligands for several TLRs are potentially anticancer agents, some of which have already been approved by the FDA, and these compounds are now undergoing clinical evaluation. There is a rationale for using these ligands as adjuvants in the treatment or prevention of gynecological cancer. Some TLR agonists that are of potential interest in the treatment of gynecological lesions include imiquimod, motolimod, cervarix, and CpG‐oligodeoxynucleotides (ODNs). In this review, we outline the different functions of TLRs in gynecological cancer with particular emphasis on the value of TLR agonists as a potential therapeutic target in the treatment of gynecological cancer. © 2019 IUBMB Life, 71(5):549–564, 2019