Cancer is a complicated family of diseases that causes major hurdles for global health. Several studies on cancer biology and cancer treatment strategies have revealed that cancer is highly genetically diverse and heterogenic in nature. The complexity of cancer is due to the highly inflammatory microenvironment which resembles wound healing process and highly acidic in nature. Hence, this condition is referred as cancer related inflammation (CRI) that drives the cancer resistance and subsequent recurrence of cancer after treatment. The major deregulated pathways associated with CRI are nuclear factor kappa B (NF-κB) and phosphoinositol-3-kinases (PI3-K) involved in cancer growth, proliferation, cancer cell survival and metastasis. Therefore, the protein factors of these pathways seem to be an attractive target for the molecular targetted therapy for cancer. However, efficient cancer treatment relies on the stages of cancer and the response to the treatment. Hence, cancer specific inflammatory components are the major targets for drug discovery, development and associated clinical trials.
One of the most deadly illnesses in the world remains cancer. New drugs with novel modes of action are urgently needed, recently, much work has been done on novel anticancer molecules derived from natural origins, particularly plants, microorganism and marine organisms. Marine natural products are repositories of novel bioactive metabolites containing different classes of bioactive substances and drug leads. This book chapter highlights the influence of marine organisms, with a specific focus on the ocean resources of marine plants, bacteria, algae, fungi, actinomycetes, sponges, soft corals, diatoms and ascidians, calculating above 90% of the overall ocean biomass. The cell lines and preclinical anti-cancerous effects of marine natural products were first introduced; their activity in preventing tumour development and associated compound-induced apoptosis and cytotoxicity was addressed. They are taxonomically distinct, having a high degree of efficiency and novel chemical structures that are pharmacologically active, creating tremendous potential for the progress of new anticancer molecules. These molecules have numerous pharmacological potentials, such as antioxidant, anti-tumour and antibacterial. Several marine anticancer agents have recently been extracted, characterized, described and are currently being studied for a clinical study. In this book chapter, we have attempted to assemble knowledge about the anticancer potential of marine products in a diversity of flora and fauna, as well as their probable mechanism of action. The molecular mechanisms that underpin the biological effects are also discussed. Finally, it addresses therapeutic methods and the present use of drugs extracted from the marine source, its future direction and limitations.
Rhenium-based cancer drugs seem to be alternative drug candidates for platinum-based drugs in the treatment of cancer. Rhenium based anticancer compounds have attracted several researchers due to their various properties and wide-ranging applications as prodrug, drug conjugates, targeted delivery, imaging and cancer killing capacities. An array of rhenium compounds displays promising cytotoxic and phototoxic properties towards cancer cells. Re-complexes with aromatic or heteroaromatic ligands like polypyridine complexes, octahedral and tris (hydroxymethyl) phosphine(THP) have prodrug properties which upon irradiation, exhibits cytotoxicity activities. PentylcarbanatoRe(I) diimine complexes, 2-(acetyloxy) benzoate Re(CO3), Re(CO3) pentylcarbonato complexes, [Re(CO)3(2-amino-4-phenyl amino-6-(2-pyridyl)-1,3,5-triazine)Cl] and Thiophene-2-carbohydrazide Re(V) complexes exhibits strong DNA binding activities. The 2-acetylpyridine-derived hydrazones Re(CO)3, Re(I) polypyridyl complexes and fac-[Re(CO)3(phen)] carboxy lato complexes were conjugated with aspirin reported as anti-inflammatory drugs. OxoRe(V) complexes with 3,3′-thiodipropanethiol tridentate ligands have been reported to inhibit the cathepsin B and K. Similar, Re-based complexes are synthesised using various ligands and that exhibit selectivity, controlled release and high efficacy potentials. However, still this research is at the preclinical studies. Re-based complexes have well-documented for antioxidant, drug delivery, selective anticancer activities, anti-inflammatory, DNA binding and damage inducing potential depending on the type ligand-Re complexes to contribute to cancer therapy. Thus, Re-compounds can be utilised in targeted therapies through coupling them with the biomolecules especially proteins and anticancer drugs. Among them, diselenium-rhenium complexes have selectivity and reduce the stress in the tumor environment to down regulate the breast cancer specific inflammatory cytokines to enhance the anticancer activity. Therefore, rhenium-based drugs are promising drugs candidate other than platinum-based drugs.
Animal models are useful tools for understanding cancer biology and genetics and serve as an essential platform for the preclinical development of anticancer therapeutics. In this context, cancer-bearing patient-derived xenograft (PDX) models, also called cancer avatars, have successfully replaced the traditional cell linederived models in recent years. PDX-based studies are now widely used for preclinical testing of novel treatments as well as tailoring personalized medicine. For anti-cancer research, however, the use of PDX models propagated from a unique patient does not fully represent the true therapeutic efficacy and toxicity of a drug. That is why many studies in this format later failed to show efficacy and safety in human clinical trials. Hence, the concepts of PDX clinical trials and co-clinical trials have gained importance and prospered in recent years. A PDX clinical trial implies investigation on a set of PDXs originated from multiple patients prior to an early phase human trial, whereas a co-clinical trial refers to drug response assays, in parallel and simultaneously with a human clinical trial, on a set of PDX models established from the same clinical trial participants. A carefully designed PDX- /co- clinical trial requires a meticulous calculation of the sample size, enrollment of pathologically and molecularly diverse patients, and selection of suitable endpoints and outcome measures. With a special focus on PDX clinical trial design in anti-cancer research, this chapter specifically addresses how to develop cancer-bearing PDX models, what to consider in characterizing them, how to track their fidelity to the parental tumor, how to estimate the number of animals included in a PDX trial, how to achieve greater power in the translation of final outcomes, what are the minimum endpoints to be considered, and what measures are preferred for evaluating the response to therapeutic interventions.
Background: Chronic lymphocytic leukemia (CLL) affects lymphoid cells and has a different chronic course. Some patients die due to the rapid progression of disease despite therapeutic measures. Therefore, it is necessary to identify, predict the disease, and seek new therapeutic strategies. Introduction: Fractal geometry can be introduced as one of the most efficient methods to study the control of CLL in this type of cancer. The present research, presenting an appropriate model for investigating the possibility of CLL control using the fractal parameter. Method: First, blood samples of the 30 healthy and 30 CLL samples with leukemia undergoing treatment were selected randomly. Second, the digital images were prepared using an optical microscope with a magnification of X100. Next, the fractal dimension of the lymphocyte nucleus of healthy and leukemia undergoing treatment was calculated using fractal software. Finally, the results were analyzed, and the fractal parameter of Neoplastic lymphocytes detection (λnld) was introduced and was calculated. Result: The probability of CLL development increases with an increase in fractal parameter of Neoplastic lymphocytes detection (λnld). If the λnld value decreases during the CLL treatment, then the CLL was controlled. Full recovery occurs when λnld is smaller than the unit. Conclusion: The average fractal dimension of the healthy lymphocytes and CLL nucleus and the fractal parameter of Neoplastic lymphocytes detection (λnld) in this research were 1.781992 ± 0.046178, 1.801322 ± 0.042357 and 0.21833 respectively. Because the λnld is smaller than the unit, the full recovery occurs for this therapeutic group
Cancer diseases affecting many organs of human body have caused a major concern among the people all over the world. The conventional anticancer drugs, although have given some relief in the patient conditions, still cannot provide reliable treatment. Moreover, these drugs produce side effects in patients and in the worse cases, the problem of rising resistance phenomena against such drugs gradually put the patients’ lives even in more serious situation. Therefore, identifying and introducing compounds with new identities to produce effective treatment with low side effects are highly demanded. Small peptides with anticancer activity have been shown to fulfill this demand. Peptides, with naturally or synthetic origin, have several advantages over common drug molecules such as low toxicity, low immunogenicity, amenable to several changes in their sequences and thus giving various homologues or analogues. Moreover, peptides in conjugation with heterocyclic active compounds and/or known anticancer drugs may result in molecules with new identities which show both benefits of individual components within their unit structures. In this regard, peptide conjugates may play a role, not only as anticancer agents but also as cell-membrane penetrating and/ or cell targeting agents to help direct cancerous tissue internalization of the known anticancer agents, and so, preventing or lowering the incidence of side effects of the anticancer drugs on healthy tissues. In this chapter on the basis of several experiments, information about various peptide categories, their analogues and conjugation with other bioactive compounds is given. The discussion is focused on the anticancer activity of peptides, those primarily known for other biological activities. Understanding the cause of these activities may help to find out and make clearer the mechanism of anticancer activity of the peptides.
Background: Plaque brachytherapy has been introduced as a treatment for ocular melanoma, an intraocular tumor, and is an available alternative to eye enucleation. Brachytherapy is one of the radiotherapy methods, which uses radioactive sources near or on the tumor. Introduction: So far, various plaques have been used to treat eye tumors. The aim of this research is the development of radioactive material for brachytherapy plaques. Method: In order to introduce and produce new brachytherapy plaques, all the isotopes of the periodic table of elements have been identified, and the mother and daughter of elements whose mother had long half-life beta decay and its daughter had a short halflife have been identified and the method of mother production has been examined. Result: After reviewing, two new 188W/188Re and 144Ce/144Pr plaques have been selected for use in brachytherapy. Conclusion: Each of the new plaques has a special advantage in comparison with old plaques. The 2D dose distribution of 188W/188Re and 144Ce/144Pr plaques in eye and tumor was obtained and was compared with old plaques.
Exosomes are extracellular vesicles that are 30-150 nm in diameter. Exosomes have recently emerged as critical mediators of cell-cell communication by the transfer of DNA, RNA, and protein structured macromolecules between cells and tissues. With the advantage of the distant endocrine signalling, cancer cells use exosomes to suppress the immune system, next contribute to the formation of premetastatic niches and angiogenesis. On the other hand, researchers have been benefited from the immunosuppressive, natural carrier, and tissue regenerating roles of exosomes and disclosed patents that are claiming the utilities of exosomes for treating chronic inflammation, autoimmunity related diseases, targeted drug delivery vehicles, and tissue regenerating agents. Moreover, the use of exosomes as vaccine components to prevent cancer, therapeutic molecules for cancer treatment, and the host of biomarkers for the diagnosis and prognosis of cancer are among the issues that are protected by recent patents. The most inspiring one among them could be the incorporation of a therapeutic siRNA that is complementary to oncogenic KRASG12D into CD47+ exosomes for the treatment of pancreatic cancer. The other one could be the demonstration of the utility of exosomes secreted from dendritic as a cancer vaccine component in phase II clinical trial. It is clear that we have started to understand the fundamentals of exosomes. However, more studies are needed to develop exosomebased cancer vaccines, drug delivery vehicles, immune-stimulating agents that evoke immune cells to kill the cancer cells, and diagnostic and prognostic markers for monitoring cancer in the next years.
The most common malignancy in the gastrointestinal tract is colorectal carcinomas (CRC), which is the second most common cancer in women and the third most in men worldwide. Adenomas are the most frequently observed precursor lesions for CRC. Two basic pathways have been defined for CRCs: the classical adenomacarcinoma sequence and serrated pathway developing from sessile serrated lesions or adenomas. In the previously reported literature, there is no potential for malignancy, but now the serrated neoplasia pathway is observed in approximately 30% of all CRCs. In large colonoscopic series studies, the prevalence of serrated polyp is approximately 20%. Colorectal serrated lesions are characterized by sawtooth or stellate morphological features of the epithelium. For sessile serrated lesion (SSL) definition, according to the World Health Organization (WHO) Classification of Tumors of the Digestive System 2019, the presence of at least 1unequivocal distorted crypt is considered sufficient for diagnosis. There is major variability in the morphology of colorectal serrated lesions or polyps, and as a consequence, a number of pathological subtypes have been described and 3 significant types have been defined; hyperplastic polyp (HP), sessile serrated lesion (SSL), and traditional serrated adenoma (TSA). HP is the most common lesion among all serrated polyps, and the potential for colorectal cancer development is very low. Improving the detection of SSLs reduces both the incidence and mortality of CRCs and reduces the risk of developing cancer of interval cancers. In this article, we will discuss serrated polyps, nomenclature, the particularly associated risk of cancer, terminology and classifications, molecular features and colonoscopic follow-up with the current designation.
The available therapy for cancers mostly revolves around chemotherapy, radiation, immunotherapy, and surgery, but these treatment modalities are not satisfactorily treating the patients and are associated with various side effects, pain, immune reduction, trauma, and also induce drug resistance in some patients. Besides, these treatments do not treat the disease's origin but eliminate the tumor itself somewhat without confirmation of avoiding its metastasis. Therefore, there is a need to develop a new effective therapy to treat cancer patients successfully. Hormones naturally present in the human body for controlling various biological and physiological functions also possess potential capabilities to treat different types of cancers. Both preclinical and clinical data show that hormones include anticancer abilities, are controlled by hormonal managing. This chapter has discussed the cellular and molecular role of different types of hormones in treating various kinds of cancers and other pertinent topics related to their impact on stem cell functionality and cancer management.
Cancer is a disease that causes a huge health burden for communities. Despite the great progress made in diagnostic tools for cancer and the advancement of treatment strategies, cancer is still one of the commonest causes of death in the world. Melatonin, a hormone produced mainly by the pineal gland, possesses an anti-cancer property. The discovery of this effect of melatonin on cancer cells was a breakthrough in the field of cancer research. Several lines of evidence support this property of melatonin, including in vitro and in vivo studies and clinical trials. This effect of melatonin was examined in various types of cancer, and a consensus has been reached with regard to its oncostatic/anti-cancer effect. Multiple mechanisms have been proposed for this effect of melatonin, among which are the anti-oxidant, antiinflammatory, anti-estrogen/androgen, anti-angiogenic, and pro-apoptotic actions of melatonin. This chapter presents an account on the anti-cancer effect of melatonin, focusing on mechanisms of action by presenting examples of cancer types, including the most common types of cancer in the world: cancers of the lung, prostate, breast, and colon, as well as ovarian cancer.
ShcA proteins are the family of adaptor proteins that mediate biological responses by transducing extracellular signals into intracellular signals. ShcA family consists of three different alternatively spliced or alternative translational initiated isoforms known as p66Shc, p52Shc and p46Shc. The p52and p46Shc isoforms are usually involved in promoting cell growth, mediating their action by activating mitogen-activated protein kinases (MAPK) and phosphoinositide-3-kinase/Akt signalling pathways. However, the p66Shc isoform acts as a dual player in cell development and is involved in stimulating both cell proliferative and apoptotic pathways. Any deregulation in the expression of ShcA proteins and pathways regulated by ShcA proteins results in the occurrence of different types of cancerous diseases, including breast cancer, thyroid cancer, prostate cancer and lung cancer. Aberrations in the expression of ShcA proteins have been demonstrated to promote key elements of cancer progression, including cell migration, cell proliferation, metabolic reprogramming, angiogenesis and tumorigenesis. Based on all these studies, the present chapter focuses on the structure of ShcA proteins and their role in promoting metastasis and progression of various cancers. Understanding the role of ShcA proteins may provide new tools for therapeutic interventions in dreadful cancer disease.
