Cancer: Unravelling Complexity, Hallmarks, and Symptom Insights
Language Edition | Pathology | Rahma Iftikhar
Cancer is a complex and diverse foe that affects millions of individuals worldwide, and years of research have revealed several underlying principles known as the hallmarks of cancer, initially described by Hanahan and Weinberg. These hallmarks provide a comprehensive framework that helps us understand the development and progression of this disease.
The Hallmarks of Cancer encompass several key capabilities that cancer cells acquire during their evolution [1]. According to Fig. 1, these include:
Sustained Proliferative Signalling:
The growth signals of regulated cell cycles that encourage controlled proliferation and tissue homeostasis are interrupted, leading to uncontrolled cell proliferation. These can be done by cytosolic signalling molecules, growth ligands or their receptors [2]. A growth ligand is ‘growth promoting’ to encourage tumour progression or ‘growth inhibiting’ to allow tumours to escape from braking signals [3].
Evading Growth Suppressors:
Cancer cells are resistant to growth-preventing signals produced by tumour suppressor genes from surrounding cells. In cancer, these genes are altered to no longer prevent cell division when cells have severe abnormalities. Cancer cells also do not contact inhibition and therefore grow and divide regardless of their surroundings [4].
Resisting Cell Death:
Apoptosis is the cell's ability to self-destruct after it has been damaged, allowing the organism to grow and develop as normal. In cancer cells, mechanisms that detect abnormalities are altered, resulting in a lack of signalling that then prevents apoptosis activation. There are also changes that may occur in the downstream signalling of proteins involved in apoptosis, preventing the process from occurring as usual.
Enabling Replicative Immortality:
Normally, cells in the body have a limited number of divisions before the cell becomes unable to divide or die. This is due to the shortening of telomeres in the DNA. Cancer cells manipulate enzymes like telomerase to increase telomere length and cause unlimited replication [5].
Inducing angiogenesis:
Angiogenesis is the process that allows the formation of new blood vessels. Cancer cells start this process to ensure a good supply of blood that carries the oxygen and nutrients needed to develop melanoma. Cancer cells do this by reducing the production of factors that inhibit blood vessel production and increase factors that promote angiogenesis in their microenvironment [6].
Activating invasion and metastasis:
Cancer cells can break away to invade their surroundings and metastasise to other body parts. This ability of the tumour helps us decide if the tumour is benign or malignant. Cancer cells allow metastasis by first invading their surrounding tissue and then invading blood vessels. They then end up in a new environment which may or may not allow the tumour to survive its harsh conditions [7].
Cancer research has revealed that there are more hallmarks beyond the original six described by Hanahan and Weinberg. Ongoing scientific investigations have identified new hallmarks, highlighting the complex nature of cancer. As shown in Fig. 2, these emerging hallmarks include deregulated cellular metabolism, tumour-promoting inflammation, genomic instability, and evasion of immune destruction. Active research in this field continues to expand our understanding and uncover novel insights. By exploring these additional hallmarks, scientists aim to develop innovative approaches for prevention, diagnosis, and treatment, offering hope for improved outcomes in the battle against cancer.
Figure 1: Hallmarks of cancer. D. Hanahan and Robert A. Weinberg, “Hallmarks of cancer: the next Generation,” Cell, vol. 144, no. 5, pp. 646–674, Mar. 2011, doi: https://doi.org/10.1016/j. cell.2011.02.013.
Figure 2: Emerging hallmarks of cancer. D. Hanahan and Robert A. Weinberg, “Hallmarks of cancer: the next Generation,” Cell, vol. 144, no. 5, pp. 646–674, Mar. 2011, doi: https://doi. org/10.1016/j.cell.2011.02.013.
The process of cancer metastasis:
Tumour cells can metastasise alone or as cell clusters. This invasion-metastasis cascade has two phases, where phase 1 consists of the physical distribution of cells from the primary tumour to distant tissues, and phase 2 consists of colonisation, where the disseminated cancer cells adapt to the new tissue microenvironment. As shown in Fig. 3, the carcinoma breaches the basement membrane and intravasates into the blood microvessels, therefore entering circulation. Then cancer cells get trapped in microvessels in other organs and extravasate into tissues to form dormant micrometastases. These may colonise the tissue and form macrometastases.
Note: : We must note that these symptoms can also be caused by other conditions. If you are experiencing any persistent symptoms, a consultation with a healthcare professional is recommended to further test and evaluate them. Early detection and treatment can significantly improve outcomes for individuals with cancer.
Figure 3: Invasion-metastasis cascade. S. Valastyan and Robert A. Weinberg, “Tumor Metastasis: Molecular Insights and Evolving Paradigms,” Cell, vol. 147, no. 2, pp. 275–292, Oct. 2011, doi: https://doi.org/10.1016/j.cell.2011.09.024.
In conclusion, ongoing research and a comprehensive understanding of cancer hallmarks provide a promising direction towards combating this formidable disease and improving the lives of those affected. Early detection, timely treatment, and continued research are vital in the fight against cancer and to provide better prospects for cancer patients in the future.
Glossary
Proliferation: Increase in the number of cells by cell division.
Cytosolic Signalling Molecules: Molecules involved in transmitting signals within the cell.
Telomeres: The ends of chromosomes consisting of repetitive sequences of non-coding DNA that protect the chromosome from damage.
Metastasis: The spread of cancer from one organ to another non-adjacent organ.
Micrometastases: small colonies of cancer cells in other tissues.
Macrometastases: large colonies of cancer cells in other tissues.
Dyspnoea: Difficulty in breathing.
What may cause cancer?
Genetic mutations
Age
Lifestyle
Hormonal factors
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Rahma is a third-year Bachelor of Science student doing a double major in Biological Sciences and Computer Science. Amongst many things, she is interested in the genetics behind diseases and the ways to cure them using technology. She is also the Outreach Coordinator for UoA Scientific this year.