The association between chronic inflammation and cancer development has been well documented. One of the major obstacles in cancer treatment is the persistent autocrine and paracrine activation of pro-inflammatory transcription factors such as nuclear factor-κB, signal transducer and activator of transcription 3, activator protein 1, fork head box protein M1, and hypoxia-inducible factor 1α in a wide variety of tumor cell lines and patient specimens. This, in turn, leads to an accelerated production of cellular adhesion molecules, inflammatory cytokines, chemokines, anti-apoptotic molecules, and inducible nitric oxide synthase. Numerous medicinal plant-derived compounds have made a tremendous impact in drug discovery research endeavors, and have been reported to modulate the activation of diverse oncogenic transcription factors in various tumor models. Moreover, novel therapeutic combinations of standard chemotherapeutic drugs with these agents have significantly improved patient survival by making cancer cells more susceptible to chemotherapy and radiotherapy. In this review, we critically analyze the existing literature on the modulation of diverse transcription factors by various natural compounds and provide views on new directions for accelerating the discovery of novel drug candidates derived from Mother Nature.
Antiphospholipid antibodies (aPLs) are autoantibodies with laboratory significance in developing thrombosis and pregnancy morbidity in antiphospholipid syndrome (APS). High prevalence of aPLs namely - anticardiolipin, anti-β2-glycoprotein I, lupus anticoagulant, antiphosphatidylcholine, antiphosphatidylserine, antiphosphatidylinositol, antiphosphatidylethanolamine and antiprothrombin antibodies have been observed in patients with different types of haematological malignancies and solid tumours. Although cancer patients have high risk of developing thrombosis, the risk becomes even higher in aPLs carriers. Although the relationship between aPLs and cancer has to be further investigated, however, the presence of aPLs in neoplastic patients can possibly increase the risk of developing thrombosis. As the pathogenic role of aPLs in cancer is still a matter of debate, more researches should be conducted on the association between the aPLs and malignancies towards the potential impact on understanding the pathogenicity and treatment when cancer and APS coexists.
Ginger is a spice that is renowned for its characteristic aromatic fragrance and pungent taste, with documented healing properties. Field studies conducted in several Asian and African countries revealed that ginger is used traditionally in the management of cancer. The scientific community has probed into the biological validation of its extracts and isolated compounds including the gingerols, shogaols, zingiberene, and zingerone, through in-vitro and in-vivo studies. Nonetheless, an updated compilation of these data together with a deep mechanistic approach is yet to be provided. Accordingly, this review highlights the mechanisms and therapeutics of ginger and its bioactive compounds focused on a cancer context and these evidence are based on the (i) cytotoxic effect against cancer cell lines, (ii) enzyme inhibitory action, (iii) combination therapy with chemotherapeutic and phenolic compounds, (iv) possible links to the microbiome and (v) the use of nano-formulations of ginger bioactive compounds as a more effective drug delivery strategy in cancer therapy.
Oral squamous cell carcinomas (OSCC) are a heterogeneous group of cancers arising from the mucosal lining of the oral cavity. A majority of these cancers are associated with lifestyle risk habits including smoking, excessive alcohol consumption and betel quid chewing. Cetuximab, targeting the epidermal growth factor receptor was approved for the treatment of OSCC in 2006, and remains the only molecular targeted therapy available for OSCC. Here, we reviewed the current findings from genomic analyses of OSCC and discuss how these studies inform on the biological mechanisms underlying OSCC. Exome sequencing revealed that the significantly mutated genes are mainly tumour suppressors. Mutations in FAT1, CASP8, CDKN2A, and NOTCH1 are more frequently found in OSCC when compared to non-OSCC head and neck cancers and other squamous cell carcinomas, and HRAS and PIK3CA are the only significantly mutated oncogenes. The distribution of these mutations also differs in populations with distinct risk habits. Gene expression-based molecular classification showed that OSCC can be divided into distinct subtypes and these have a preferential response to different types of therapies, suggesting that these classifications could have clinical implications. More recently, with the approval of checkpoint inhibitors for the treatment of cancers including OSCC, genomics studies also dissected the genetic signatures of the immune compartment to delineate immune-active and -exhausted subtypes that could inform on the immune status of OSCC patients and guide the development of novel therapies to improve response to immunotherapy. Taken together, genomics studies are informing on the biology of both the epithelial and stromal compartments underlying OSCC development, and we discuss the opportunities and challenges in using these to derive clinical benefit for OSCC patients.