Frontiers in Clinical Drug Research - Anti-Cancer Agents

According to the World Health Organization (WHO) report, cancer is one of the leading causes of death, particularly in developing countries. The malignant proliferation and survival of cancer cells rely on the biosyntheses of proteins, nucleotides, and fatty acids. Accumulating pieces of evidence demonstrate that amino acid restrictions are valuable for cancer interventions. Meanwhile, folk remedies using dietary strategies are abused and lack solid rationale. To clarify what, why, and how the potential strategy is, here, we update and recommend a dietary strategy for cancer therapy: the intermittent dietary lysine restriction with the normal maize (lysine deficiency) as an intermittent staple food for days, weeks, or even months, will be a feasible strategy for cancer intervention. In addition, dietary and immunomodulatory supplements, such as low protein starchy foods, vegetables, fruit, and mushrooms, may serve as supplements to satisfy the daily needs of micronutrients and the plethora of dishes.

Cancer is perhaps one of the gravest challenges that humanity has been facing for centuries. According to the World Health Organization (WHO), cancer is the second leading cause of death worldwide. Nanotechnology has revolutionized cancer research by providing a targeted and selective alternative to conventional treatment modalities and drug delivery protocols with lesser side effects and negligible systemic toxicity. Nanoparticles (NP), particularly noble metal nanoparticles, are one such competent alternatives that have been extensively studied and applied to various aspects of cancer therapy with exemplary results. Nanoparticles of noble metals such as silver, gold, and platinum possess unique properties like small size, non-toxicity, high surface-to-volume ratio, tunable optical properties,and ease of functionalization with antibodies, nucleic acids, nucleotides, and peptides. These nanoparticles have an inherent advantage over traditional moieties regarding intracellular delivery due to their small size. This proved very helpful in the gene silencing method involving smallinterfering RNA for the down-regulation of gene expressions in cancerous cells. In particular, gold nanoparticles (AuNP) are highly selective radiosensitizers, whereas silver nanoparticles (AgNP) have anti-proliferative and apoptosis-inducing effects on cancer cells. Platinum nanoparticles (PtNP) and AuNPs display exceptional thermoplasmonic properties and hence are being used effectively in cancer photo thermal therapy (PTT). PtNPs have the potential to amplify the efficacy and selectivity of the hadron therapy. This chapter will elaborate on all the above-mentioned roles of noble metal NPs in creating an effective anti-cancer therapy paradigm focusing on theranostics and drug delivery mechanisms.

There is a growing demand for the development of new anticancer drugs owing to the worldwide increase in cancer mortality. Algal polysaccharides, such as fucoidan, alginate, laminarin, carrageenan, porphyran, ulvan and calcium spirulan, have been recognized as natural products with potential good anticancer properties against a variety of cancer cell lines in vitro and in vivo. Therefore, they can be used for the development of natural anticancer drugs with fewer side effects than synthetic ones. Additionally, algal polysaccharides can be used as an adjuvant treatment to mitigate undesirable side effects and promote the anticancer properties of clinical anticancer drugs. This chapter focuses on the recent anticancer properties of algal polysaccharides from different algal groups as well as their mode of action.

Cancers and cardiovascular disease continue to be leading causes of mortality worldwide despite unrelenting efforts to improve therapeutic strategies in both. Ironically, cardiac adverse effects of anticancer drugs result in an ever-increasing proportion of deaths in cancer survivors. Doxorubicin, one of the earliest anthracycline chemotherapeutic agents which has been in clinical use since the 1970s, is notorious for causing cumulative dose-dependent irreversible cardiac damage, traditionally termed “type I” cancer therapy-related cardiotoxicity. In the late 1990s, the approval of trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), initiated an era of targeted anticancer therapy with the hope of eradicating off-target adverse effects. Unfortunately, trastuzumab treatment leads to the distinctive “type II” cancer therapy-related cardiotoxicity. As an acknowledged type I and type II cardiotoxic anticancer agents, doxorubicin and trastuzumab have been intensely investigated with regard to the complex mechanisms of their effects on the heart, yet complete understanding remains elusive. This chapter comprehensively summarizes current mechanistic insights regarding the cardiotoxicity of doxorubicin and trastuzumab, encompassing the pathophysiology of contractile dysfunction (cardiomyopathy) and electrical disturbance (arrhythmia). Gaps in knowledge and recommendations for future advances are also discussed to encourage further investigation in the field, with the ultimate goal being the effective prevention and/or treatment of cancer therapy-induced cardiac complications.

Cancer is a serious health issue that remains a significant cause of mortality around the world. Psychosocial support, surgery, radiation, and chemotherapy are common cancer treatments. However, because of the rising rate of cancer-related mortality and the adverse or toxic side effects of cancer chemotherapy and radiation therapy, new anticancer compounds obtained from nature, particularly plants, are currently being researched. Phytochemicals, which are naturally occurring plant substances, are important sources for new drugs and cancer treatment. Phytochemicals are selective in their actions, acting only on tumour cells and not on healthy cells. These phytochemicals act by modulating molecular pathways involved in cancer growth and progression. Anthraquinones are a class of phytochemicals that have a wide range of biological functions as well as anticancer action. Emodin is a natural anthraquinone derivative found in Rheum palmatum, Polygonum cuspidatum, Polygonum multiflorum and among other commonly used Chinese medicinal plants. Evidence indicates that emodin has a wide spectrum of pharmacological properties, including hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities. Emodin has also been reported to have anticancer properties in a variety of malignancies, including lung, liver, and pancreatic tumours. Anticancer properties of emodin have been studied in a variety of biological pathways. This chapter aims to comprehensively summarize the anti-proliferative and anti-carcinogenic properties of emodin.