The Cellular Basis of Cancer

The progression of cancer originates from a series of molecular events that results in the uncontrollable division and distribution of malignant cells (Nash, 1984). As these cells begin to migrate to different locations, new heritable characteristics start to develop that allow this disease to manifest, regardless of the cell’s surroundings. These cellular irregularities typically result from mutations in protein-encoded genes that regulate normal cell division, repair DNA damage and control the selective replication of healthy cells. Regardless of the type of cancer, it is ultimately the changes in cell anatomy and DNA sequencing that contributes to the development of this disease. Therefore, even though environmental and lifestyle factors do heighten the likelihood of certain types of cancers, one must first consider the cellular basis of the issue in order to gain a deeper understanding of the nature of this disease.

The human genome provides the genetic building blocks required for cells to specialise and regulate normal, cellular behaviour. In relation to cancer, an approximate of 35, 000 genes have been identified, which when altered, provide the basis of variations for this disease (Vogelstein et al., 2013). These alterations are broadly organised into district groups, that allow for the systematic analysis & exploration of the following key areas: oncogenes, anti-oncogenes, DNA repair genes and the cell cycle.

In a healthy cell, proto-oncogenes synthesise proteins, which promote cell division and are programmed to induce apoptosis, where necessary (Stine et al., 2015). This particular gene provides information to the nucleus of a cell through a process known as signal transduction cascade. Signal transduction cascade is a series of biochemical reactions in which signal activated receptors, signal carrying proteins and the transcription of DNA to messenger RNA, active the genetic information needed for cell division (Stine et al., 2015). This sequential pathway, from  stimuli to nuclei, relies on the previous action to activate the next, and variations to this precise procedure can result in mutated forms of proto-oncogenes, called oncogenes. Oncogenes exhibit irregular behaviours that are activated in two primary circumstances; either variation in chromosome rearrangement, that allows the sporadic activation of genes, or the presence of extra genes, which can result in the over-production of certain proteins (Ben-Yosef et al., 1998). The overarching notion is that the inactivity of gene regulators contributes to the cellular changes that ultimately form the foundation for malignant tumours. In this regard, mutations to MYC and RAS genes play particular roles, as they regulate normal cell behaviour through genetic intervention. MYC is a type of proto-oncogene that encodes nuclear phosphoproteins, which along with a transcription factor, determines cell proliferation and apoptosis (Ben-Yosef et al., 1998). MYC has been linked to over 50% of cancers (Chen, Liu and Qing, 2018), as a cell’s inability to regulate gene expression means that normal behaviour is overridden, and the likelihood of mutation increases. RAS, on the other hand, regulates signal transduction and cell multiplication, which in recent studies has been associated with 20-30% of cancers (Pellicer, 2011), with its highest frequency being in 80-90% of pancreatic cancers cases (Pellicer, 2011). The issue of MYC and RAS mutations is further solidified, as most oncogenes are dominant mutations, meaning that a copy of this genetic variance is enough for the manifestation of that growth trait in other cells (Pellicer, 2011). Ultimately, mutations in the genetic building blocks of a cell facilitate the disposition for cancer, as variances in proto-oncogenes mean that the uncontrollable division and distribution of malignant cells replaces normal cellular behaviour.

Tumour suppressor genes, or anti-oncogenes, synthesis proteins that either halt the cell cycle and/or induce apoptosis, to stop the duplication of genetic errors in cell proliferation, ultimately controlling tumour formation (Engelberg, 2004). Variances in this gene group results in abnormal cell behaviour, where the ability to control normal growth and division is inhibited. In normal situations, the products of anti-oncogenes act upon the cell membrane, to regulate specific membrane receptors like those associated with epidermal growth factor molecules (EGF) (Engelberg, 2004). EGF is an extracellular protein ligand that stipulates cell growth and differentiation, that when amplified and over-expressed, due to the deamination of tumour suppressor genes, has been associated with cancer. However, this loss in cell functionality, through the mutation of tumour suppressor genes, is recessive in nature, meaning that this trait is not expressed unless both copies of the gene are altered (Engelberg, 2004). Within an anti-oncogenes perspective, the “Two-Hit Hypothesis” is a theory used to explain the formation of these malignant cells (Testa and Hino, 2003). The theory suggests that only if both the genes are mutated will the trait express itself and will the cell grow uncontrollably. The mutated genes can either be inherited from a germ line cell, or mutated in a somatic cell, during the life span of the individual. Though it is not always the case that the first gene mutation must be inherited, a familial history of genetic irregularities does significantly heighten an individual’s chances for cancer (Testa and Hino, 2003). For example, regardless of the time difference between the mutations, hereditary breast cancer arises from a mutation in both BRCA1 copies (Testa and Hino, 2003). This is of particular interest as it showcases that both genes have the capacity to individually contribute to the repairing of cellular and molecular issues, like double-stranded DNA breaks. Overall, tumour suppressor genes have evolved to act as a roadblock against the development of cancer. Having the ability to control the duplication status of cells and allow for the independence of genes, means that the formation of tumours have to arise from very specific conditions, such as inheritance of mutations or exposure to particular agents.

DNA repair genes maintain chromosome structures and work towards mitigating the likelihood of damage (Cleaver, 2005). Mutations to this group of genes come both from changing internal circumstances and environmental factors, such as exposure to radiation and toxic chemicals (Gao, Herman and Guo, 2016). The deamination, or decreased efficiency of DNA repair genes means that the capacity to which a cell can repair itself is overshadowed by the accumulation of genetic errors. As these changes cannot be addressed while the DNA repair gene is incapacitated, the frequency of cancer-related changes in a cell drastically increases (Gao, Herman and Guo, 2016). For example, defects in the DNA repair gene Xeroderma Pigmentosum (XP), are associated with higher incidence rates of skin and mucous membrane cancers, as the genomic instability makes it difficult for the cell to operate in the presence of UV light (Lehmann, 2003). Additionally, DNA repair gene defects can also be inherited from germ line cells, and immediately affect the distribution of genetic information. For example, Bloom syndrome is a recessive disease that greatly increases an individual’s chances of cancer due to disruption of the BLM gene that is necessary for maintaining structurally sound chromosomes (Rivera-Begeman et al., 2007). Holistically speaking, it is both a cell’s inability to repair DNA and appropriately apoptosis, when defects are recognised, that contributes to the basis of this issue.

Finally, in order to ascertain a complete understanding of the cellular basis of cancer, the cell cycle must be understood so the process of cell maturity in the context of cancer can be looked at. The cell cycle is a normal process whereby cells grow and divide in accordance to regulatory proteins that control the timing of phase transitions (Molinari, 2000). This tight regulation serves of great importance in the mitigation of diseases as regular checkpoints establish the constant re-evaluation of a cell’s health. Cyclin-dependant kinases are multipurpose enzymes that form different complexes with particular cyclin proteins that in turn control external growth factors, apoptosis and easement of cell division (Sánchez-García, 2012). The synthesis of external growth factors is required by cells in order to divide. In this process, p53 is a vital protein that regulates this behaviour through the introduction of a transcription factor. This factor subsequently activates a pathway of other proteins that are required for movement through the Gap 1 phase of the cell cycle (Sánchez-García, 2012). In the cycle of healthy cells, this stage slows down progress and allows time for DNA to be repaired, and apoptosis to occur if the damage is too extensive (Sánchez-García, 2012). For cancerous cells, this cycle operates differently, where by affected cells become independent and are no longer reliant on the activation/deactivation of a protein’s functionality (Sánchez-García, 2012). This plays a pivotal role in the proliferation of cancer, as cells cannot be destroyed by the ordinary standards found within a cell’s genetic code (Molinari, 2000). In a nutshell, this means that mutations will be replicated into daughter cells, chromosomal aberrations will become more prevalent throughout the body and, for the individual, the prospect of cancer greatly increases.

Overall, the development of cancer arises from cell mutation, DNA variations and chromosomal difference that result from duplicating cells. By looking at this issue through a cellular and molecular perspective, a solid scientific foundation has been laid out. By recognising and exploring the heritable characteristics that allows cancer to manifest, as well as highlighting the key areas where mutations are susceptible, a deeper understanding of the nature of this disease has been ascertained.



Nash, J. (1984). CANCER PREVENTION AND DETECTION. Cancer Nursing, 7(2), p.163. Vogelstein, B., Papadopoulos, N., Velculescu, V., Zhou, S., Diaz, L. and Kinzler, K. (2013). Cancer Genome Landscapes. Science, 339(6127), pp.1546-1558. Cleaver, J. (2005). Mending human genes: A job for a lifetime. DNA Repair, 4(5), pp.635-638. Gao, D., Herman, J. and Guo, M. (2016). The clinical value of aberrant epigenetic changes of DNA damage repair genes in human cancer. Oncotarget, 7(24). Lehmann, A. (2003). DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. Biochimie, 85(11), pp.1101-1111. Menck, C. and Munford, V. (2014). DNA repair diseases: what do they tell us about cancer and aging?. Genetics and Molecular Biology, 37(1 suppl 1), pp.220-233. Rivera-Begeman, A., McDaniel, L., Schultz, R. and Friedberg, E. (2007). A novel XPC pathogenic variant detected in archival material from a patient diagnosed with Xeroderma Pigmentosum: A case report and review of the genetic variants reported in XPC. DNA Repair, 6(1), pp.100-114. Testa, J. and Hino, O. (2003). Tumor suppressor genes and the two-hit model of recessive oncogenesis: Celebrating Alfred Knudson's 80th birthday. Genes, Chromosomes and Cancer, 38(4), pp.286-287. Engelberg, D. (2004). Stress-activated protein kinases?tumor suppressors or tumor initiators?. Seminars in Cancer Biology. Jankowski, J., McMenemin, R., Hopwood, D., Penston, J. and Wormsley, K. (1991). Abnormal expression of growth regulatory factors in Barrett's oesophagus. Clinical Science, 81(5), pp.663-668. Olapade-Olaopa, E. (2001). The expression of a mutant epidermal growth factor receptor in prostatic tumours. BJU International, 87(3), pp.224-226. Ben-Yosef, T., Yanuka, O., Halle, D. and Benvenisty, N. (1998). Involvement of Myc targets in c-myc and N-myc induced human tumors. Oncogene, 17(2), pp.165-171. Stine, Z., Walton, Z., Altman, B., Hsieh, A. and Dang, C. (2015). MYC, Metabolism, and Cancer. Cancer Discovery, 5(10), pp.1024-1039. Chen, H., Liu, H. and Qing, G. (2018). Targeting oncogenic Myc as a strategy for cancer treatment. Signal Transduction and Targeted Therapy, 3(1). Pellicer, A. (2011). RAS Genes. Encyclopedia of Cancer, pp.3181-3184. Molinari, M. (2000). Cell cycle checkpoints and their inactivation in human cancer. Cell Proliferation, 33(5), pp.261-274. Sánchez-García, I. (2012). Understanding telomerase in cancer stem cell biology. Cell Cycle, 11(8), pp.1479-1480.