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Simple Summary The exposure of cancer cells to cadmium compounds may be associated with the acceleration of tumor progression. It is known that cadmium is a transcriptional regulator, and the study of differentially expressed genes has enabled the identification and classification of cadmium-associated molecular signatures as useful biomarkers that are potentially transferable to clinical research. This review recapitulates the studies that report the detection of such signatures in breast, gastric, colon, liver, lung, and nasopharyngeal tumor cell models, as specifically demonstrated by individual gene or whole genome expression profiling. Abstract The exposure of cancer cells to cadmium and its compounds is often associated with the development of more malignant phenotypes, thereby contributing to the acceleration of tumor progression. It is known that cadmium is a transcriptional regulator that induces molecular reprogramming, and therefore the study of differentially expressed genes has enabled the identification and classification of molecular signatures inherent in human neoplastic cells upon cadmium exposure as useful biomarkers that are potentially transferable to clinical research. This review recapitulates selected studies that report the detection of cadmium-associated signatures in breast, gastric, colon, liver, lung, and nasopharyngeal tumor cell models, as specifically demonstrated by individual gene or whole genome expression profiling. Where available, the molecular, biochemical, and/or physiological aspects associated with the targeted gene activation or silencing in the discussed cell models are also outlined.

Recent years have seen the idea of a close association between nutrition and the modulation of cancer development/progression reinforced. In fact, an increasing number of experimental and epidemiological evidence have been produced supporting the concept that many different bioactive components of food (e.g. polyphenols, mono- and polyunsaturated fatty acids, methyl-group donors….) may be implicated in either the promotion of or the protection against carcinogenesis. At cellular level, such compounds can have an impact on different but sometimes intertwined processes, such as growth and differentiation, DNA repair, programmed cell death, and oxidative stress. In addition, compelling evidence is starting to build up of the existence of primary epigenetic targets of dietary compounds, such as oncogenic/oncosuppressor miRNAs or DNA-modifying enzymes, which in turn impair gene expression and function. This editorial aims to summarize the themes of the 31 papers (20 original articles and 11 reviews) published in the special issue “Role of Natural Bioactive Compounds in the Rise and Fall of Cancers” presenting the latest findings on the intracellular pathways and mechanisms affected by selected natural molecules influencing the fine-tuning of cancer phenotype.

Hormones, i.e., the products of specialized endocrine cells which spread throughout the body via the bloodstream, control the normal development and growth of organisms at the embryo-fetal stage and, in adult life, regulate, integrate, and coordinate a range of different physiological processes which concern virtually all body tissues. They exert their biological effects by interacting with either surface or intracellular receptors, thereby activating signalization pathways [1]. For example, steroid hormones, such as those released by the adrenal glands, testes and ovaries, once freely crossed through the plasmalemma, bind to receptors that act as ligand-dependent transcriptional regulators and influence the expression of a plethora of target genes responsible for diversified biological responses, including sexual differentiation, osmoregulation, metabolism and developmental roles in various fetal systems among others [2,3].

Parathyroid hormone-related protein (PTHrP), classically regarded as the mediator of the humoral hypercalcemia of malignancy syndrome, is a polyhormone that undergoes proteolytic processing into smaller bioactive forms. These bioactive forms comprise an N-terminal- as well as midregion- and C-terminal peptides, which have been shown to regulate various biological events, such as survival, proliferation and differentiation, in diverse cell model systems, both normal and pathological. A number of experimental data have demonstrated that PTHrP is also able to modulate tumor-relevant phenotypic expressions, thereby playing a role in early and advanced tumorigenesis, and in the response to treatment. In particular, interest has mainly been focused on the effects of PTHrP on cell proliferation/apoptosis, migration and invasion, which are the main roles involved in cancer development in vivo. The objective of this review is to discuss collectively the literature data on the molecular and biochemical basis of the mechanisms underlying the different, and sometimes opposite, effects exerted by PTHrP on various neoplastic cytotypes, with some final comments on both present and potential utilization of PTHrP as a target for anti-cancer therapy.