Genes and heredity in breast cancer
A. R. Genazzani in Hormone Replacement Therapy and Cancer, 2020
A cancer cell is initiated when, after a series of specific mutations, it acquires the neoplastic genotype. Initiation is considered a common event, but, fortunately, in a very large number of cases it does not give origin to a tumor, in fact, the transformed cell is eliminated through the normal mechanisms of defense that recognize it as ‘different’. Neoplastic growth starts if the entire cell compartment, of which the transformed cell is a part, is stimulated (promoted) to proliferate; in human cancer, promoting agents are of two main types: chronic inflammation and hormones. The growth factors produced by chronic exudates represent a strong stimulus for cell proliferation; this takes place, for example, in two human cancer models, as squamous lung cancer and squamous cervical cancer. On the other hand, steroid hormones exert a powerful promotion effect on mammary epithelial cells, and represent the main promoting agents for breast carcinoma. Progression is the last and longest phase in the cancer cycle, and can be defined as all neoplastic steps from the beginning of cell growth to the eventual acquisition of the metastatic phenotype; its early stage comprises all degrees of in situ epithelial proliferation (in breast ductal carcinoma, as an example, these are florid hyperplasia, atypical hyperplasia of various grades, in situ carcinoma), infiltrating cancer is the intermediate stage of tumor progression and metastasis is the late stage.
Biologically Targeted Agents in Head and Neck Cancers
John C Watkinson, Raymond W Clarke, Terry M Jones, Vinidh Paleri, Nicholas White, Tim Woolford in Head & Neck Surgery Plastic Surgery, 2018
Cancer is a genetic disease that develops when the information in cellular DNA is corrupted or wrongly decoded. This leads to altered patterns of gene expression and derangement of normal protein function. Simply stated, genetic changes leading to cancer mediate two general effects: (i) overactivity of genes that stimulate cell growth, survival and spread; and (ii) underactivity of genes that repress these processes. Through these changes, cancer cells acquire properties that allow them to grow in an uncontrolled fashion, invade adjacent normal tissues, recruit their own blood supply, avoid immune detection and destruction, spread to distant sites and develop resistance to anticancer treatments. By understanding these processes, we have an opportunity to design and implement new classes of so-called targeted therapies that will exploit the fundamental biological differences between malignant and normal cells.
Gold Nanoparticle–Assisted Radiation Therapy
Pandit B. Vidyasagar, Sagar S. Jagtap, Omprakash Yemul in Radiation in Medicine and Biology, 2017
Nanotechnology is a rapidly growing field with ramifications in medicine, chemistry, biology, engineering, and materials science. Nanomaterials possess unique optical, electrical, and magnetic properties that are different from bulk material of the same chemical. As a result, they are being developed for various applications in medicine such as targeted drug delivery, diagnostics, and therapy. Various metallic nanoparticles are being tested for medical applications. Among them, gold nanoparticles are considered to be biologically safe and biocompatible materials and have attracted considerable attention in cancer imaging and radiation therapy (RT). RT is one of the modalities used in treating cancer. In RT the dose delivered by ionizing radiation can be enhanced in the presence of radio-modifying materials (e.g., high −z number) in cancer cells. Therefore, it is possible to eliminate cancer cells from the tumor. This chapter discusses the effectiveness of gold nanoparticle-assisted radiation therapy.
How to rekindle drug discovery process through integrative therapeutic targeting?
Published in Expert Opinion on Drug Discovery, 2018
Ashok Vaidya, Anuradha Roy, Rathnam Chaguturu
Genetics is often the route chosen for target identification and validation, a result of Genome-Wide Association Studies (GWAS) linking certain genetic variants or mutations to a disease condition or having a direct biomarker in the gene causing the disease. While we utilize the results of genome wide sequencing data and incorporate gene expression data within the rationale for pursuing drug discovery efforts of specific pathways and proteins, the use of genetics to aid in finding a cure is often left behind. Compensatory mutations that can rescue the original mutation is an area that can add another possible avenue to consider when searching for a disease-modifying drug. Can a drug against a protein in another pathway solve/prevent the condition caused by the original mutation? Cancer cells have a mutation which in part is responsible for their phenotype. When this mutation is combined with another mutation (which also by itself has no effect on the cell) the cell is doomed – hence being synthetic lethal. Finding compounds that cause this effect is a potential source of new drugs and a new mechanism of action for treating cancers. If two mutations can work together to provide lethality, could the reverse not also be true – synthetic health? This approach would seek non-related mutations which cure the phenotypic disease or at least slow it down. This strategy could also be used in drug–drug combination types of approaches and creation of chimeric compounds [2].
MicroRNA-143 inhibits proliferation and migration of prostate cancer cells
Published in Archives of Physiology and Biochemistry, 2022
Elshan Bajhan, Behzad Mansoori, Ali Mohammadi, Dariush Shanehbandi, Vahid Khaze Shahgoli, Elham Baghbani, Khalil Hajiasgharzadeh, Behzad Baradaran
MicroRNAs (miRNAs) are small noncoding RNAs with 18–25 nucleotides (Shenouda and Alahari 2009) and categorised into two classes of oncogenic and tumour suppressor miRNAs (Croce 2009). The results of studies in recent years have changed the traditional thought regarding cancer. Nowadays it is obvious that the cancer cells are developed by mutations of several genes, and in fact, cancer is genetically very complicated (Mansoori et al. 2015). About 30% of the human genes are controlled by miRNAs, thus, these molecules can have a role in different and important processes such as proliferation, differentiation, apoptosis, angiogenesis, metabolism, viral replication, immune responses as well as stress responses (Reid et al. 2011, Bhayani et al. 2012). Treatment based on miRNAs could be carried out to returning the expression level of the tumour-associated genes to their original level (Gerlinger et al. 2012). Like other cancers, tumour-suppressive miRNAs in PC consist of miRNAs whose levels of expression have an adverse correlation with the rate and severity of cancer (Iio et al. 2013, Wu et al. 2013). Since these miRNAs target the oncogenic signalling pathways leading to growth, proliferation, and invasion of cancer cells, they are very effective in the prevention of PC, and also they can be used to treat or control the disease in different ways (Mansoori et al. 2015).
Dynamics of transforming growth factor β signaling and therapeutic efficacy
Published in Growth Factors, 2023
Siqi Wu, Rodney Brian Luwor, Hong-Jian Zhu
Despite the fact that more experimental results are required to obtain a better understanding of TGFβ signalling dynamics, logical hypotheses can be formed based on the known functions of TGFβ and its association with different stages of malignancy. Figure 3 illustrates the hypothetical explanations for suspected dynamic TGFβ signalling and the potential reasons for the lack of success of anti-TGFβ-targeted therapies. Cancer cells are constantly experiencing stress and changes in their surrounding environment, and the adaptation to new situations requires rapid adjustment of cellular responses, which are unlikely to be controlled at the genetic level by random mutations. TGFβ is a universal regulator of cell adhesion, motility and survival, and it mediates other signalling pathways and subsequent cellular processes promptly after ligand-receptor binding, which makes it a suitable converging point for controlling cell responses and cell behavioural changes. It has already been shown that early and late-stage cancer cells respond differently to TGFβ, and on average, the increased level of TGFβ signalling is correlated with metastasis and advanced cancer (Robson et al. 1996; Ivanović et al. 2006). By dissecting each aspect of TGFβ signalling dynamics, the pro-metastatic role of TGFβ may be better explained.