Metastasis occurs when cancer cells break away from the original primary tumour and spread to other organs or tissues. This process usually signifies advanced stages of disease and poses challenges for treatment.
The below sections delve deeper into the mechanisms of metastasis, including the common sites for various cancer types, as well as possible strategies and advances in targeting the process of metastasis in cancer progression.
Metastasis is a complex process in cancer development. It happens when cancer cells from a primary tumour break away and spread to other parts of the body.1 These cells go on to multiply and then form new tumours in different organs or tissues. This makes it more difficult to treat the cancer. Metastasis can greatly impact treatment and the severity of cancer diagnosis. It often indicates advanced stages of the disease and comes with challenges that can affect treatment options due to the presence of widespread tumours. The term metastasis can be frightening; therefore, understanding what it is can be vital for patient treatment options and outcomes.
Process of metastasis
Local invasion is the first step in cancer progression to metastasis. The cancer cells separate from the primary tumour and circulate inside the body to other organs or blood vessels in the same area as the primary tumour. They can then settle and grow to form new metastatic tumours, sometimes referred to as secondary cancers or secondary tumours.2
Intravasation is the next stage in the detached cells' journey. Once they have left the primary tumour, they can enter the bloodstream through blood vessels that carry oxygen and nutrients via blood or the lymphatic system. The lymphatic system forms part of our immune system and consists of thin tubes and lymph nodes. It defends against infections and is made up of various organs. These tubes carry lymph, which is a clear fluid throughout the body, and it is here that the detached cancer cells can be transported to nearby lymph nodes or to more distant parts of the body to form metastases.2
During circulation, the detached cancer cells begin to travel to various organs and tissue systems in the body. The cells move freely through the bloodstream or lymphatic system until they exit for a new organ or tissue. These cells can travel collectively, as clusters, or as single cells. When travelling in the bloodstream or lymphatic system, detached cells face challenges, such as various immune cells in the lymphatic system.2 Examples include types of white blood cells such as lymphocytes, which are the B cells and T cells, as well as macrophages. These cells engulf and destroy cancer cells and play a vital role in the defence against cancer. However, cancer cells can also employ strategies to evade the immune system and continue spreading and growing.
During extravasation, the cancer cells exit the blood vessels or lymphatic system and enter nearby organs or tissues. It is here that they settle and begin to grow into secondary tumours at new sites.2
Proliferation and colonisation
The later steps involved metastasis. The cells that have arrived at their new location multiply and begin to form new secondary tumours. They achieve this by turning on the genes that are associated with cell growth and division. These cells continue to multiply (or proliferate) until they form what is known as a colony. This colony then forms the basis of a larger secondary tumour through the process of cell growth and division and begins to disrupt the normal functions of the organs they have settled in. As the colony grows, these cancer cells need nutrients and oxygen to survive and grow, so they release chemical signals to encourage the growth of new blood vessels in a process called angiogenesis. These new blood vessels provide a path for the nutrients and oxygen to reach the cancer cells and fuel the growth and survival of these micro-tumours.2 However, not all micro tumours form larger secondary tumours straight away. Some may lie hidden or dormant for months or years after extravasation.3
Mechanisms of metastasis
The mechanisms of metastasis are complex - involving cells breaking away from the primary tumour, surviving challenges in circulation, and adapting and growing in new locations. Both molecular and micro-environmental factors are necessary to support metastatic growth and allow cancer cells to grow and adapt away from the primary tumour.4 Depending on the abundance of nutrients available for the cell, it can influence whether the cells will go on to metastasise.5
Common sites of metastasis
Cancer can spread to virtually any part of the body. The most common sites are bone, liver, and lung. Different cancers have preferred sites in which they spread. For example, breast cancer commonly spreads to the brain as well as bone, liver, and lungs.5 Whereas, head and neck cancers commonly spread to the lungs, bone, brain, skin and soft tissue.6 It is important to remember that common sites for metastasis depend on the type of primary cancer and its stage.7 By understanding the pattern of metastatic spread, healthcare professionals can monitor specific places in the body where metastasis is likely to occur, leading to earlier detection and treatment.
Impact of metastasis on cancer treatment
Metastasis can cause significant challenges when it comes to treatment. When cancer cells spread to other organs or tissues, it makes treating the disease more complex and often requires extensive treatment plans. These treatments usually are a combination of surgery, chemotherapy, radiotherapy, or immunotherapy.8 It is also possible for the metastatic tumours to be resistant to certain treatment types which previously worked for the primary tumour. Metastasis often signifies advanced stages of disease due to the spread of the cancer. This often results in a poorer prognosis, as cancer in multiple locations makes it harder to treat than if it were in one place alone.
It can also have an impact on mental health. It can be mentally challenging for patients and families to handle the diagnosis and treatment side effects. It is common for people to struggle with their mental health upon a cancer diagnosis, especially if the cancer is advanced and includes metastasis. It requires continuous follow-up with health professionals for regular imaging and testing to guide treatment plans and monitor any further cancer spread.
Strategies for targeting metastasis
Targeting metastasis can be challenging and requires a variety of treatments and strategies. For metastatic disease, the aim is to stop the cancer from spreading and to improve the quality of life in those with the disease. Common strategies include:8,9,10,11
- Chemotherapy drugs – the use of pharmaceutical drugs that attack cancer cells, stopping them from growing and spreading further
- Radiotherapy – for some types of cancers, radiotherapy, otherwise known as radiation therapy, may be beneficial to shrink or destroy cancer cells using high doses of controlled radiation. This particular treatment has been proven beneficial in relieving symptoms of pain caused by tumours.
- Surgery – if the cancer spread is limited, meaning there are no or not many secondary tumours that have settled in other organs or tissues, surgery can be used to remove the tumour. This is not always possible, though, especially in patients where metastasis is extensive.
- Immunotherapy – a relatively new treatment is the use of the body's immune system to recognise and attack cancer cells. These include drugs such as Immune checkpoint inhibitors. These inhibitors block signals from cancer cells and immune cells that interfere with the immune system’s ability to recognise the cancer cell as harmful. By blocking the signal, the immune cells can identify these harmful cancer cells and attack them.
- Combination therapies – in some cases, healthcare professionals may decide to use a combination of treatments to increase efficacy. Some examples include combining chemotherapy with immunotherapy or surgery with radiotherapy.
It is important to remember that the choice of strategy decided upon by the healthcare provider will depend on the type of cancer, the staging, and the location of the metastases. In most cases, combination therapies are used to target and manage metastatic cancer.
Current research surrounding cancer has highlighted the difficulties in controlling metastatic spread. New approaches involving the understanding of the molecular mechanisms that drive metastasis are being investigated with the hopes of developing targeted therapies that can interrupt the process. Thus, limiting the spread of cancer.
Importance of early detection and prevention
An early cancer diagnosis can mean improved survival and better treatment options and outcomes for many.
Early detection can be via an early diagnosis and screening. For many, an early diagnosis means that the cancer will respond better to treatment and, therefore, result in a better chance of survival. Around 50% of patients are at an advanced level of metastasis by the time it is detected, so early detection is crucial.12 It also means that if found early, the chances of metastatic spread are lower. To help aid in an early diagnosis, people need to be aware of the symptoms of different types of cancers and seek appropriate medical advice if they feel they are presenting any symptoms.
Screening can also aid in early diagnosis. Many countries now offer screening services for various cancers that aim to detect any changes in cells before they become fully cancerous.12 These are otherwise known as precancerous cells. An example of this is mammography screening for breast cancer.
If an abnormal result is found after screening, a healthcare professional will order further tests to establish a diagnosis. However, screening programmes may not be appropriate for all cancers.
It is not always possible to prevent cancers from metastasising - forming new tumours. This is why early detection and treatment are important to help stop the spread of the primary tumour to other parts of the body. Treatments such as surgery for complete removal of the tumour and any possible sites of metastasis, such as at lymph nodes, can help prevent further spread. Surgery may be followed by adjuvant therapy, which is a treatment that is given after the main treatment, possibly surgery, to reduce the chance of cancer coming back. This is done by destroying cancer cells. A likely adjuvant treatment could be chemotherapy, radiotherapy or immunotherapy.
By reducing risk factors, the chance of developing certain types of cancers can also be reduced. Common risk factors associated with the development of various cancers are:13
- Alcohol use,
- An unhealthy diet,
- A sedentary lifestyle
- Air pollution.
- Controlling lifestyle risk factors, such as the ones mentioned above, has shown to have a vast influence on the development of certain types of cancers, with over 90% of cancer cases due to environmental influences.13
Detecting cancer early and reducing lifestyle risk factors are key to improving survival rates. Metastasis is a complicated process and presents many challenges when it comes to detection and treatment. It is the spread of cancer cells from a primary tumour to various other parts of the body and has a large influence on patient survival. Understanding the mechanisms and how metastasis develops in the body is key for paving the way to a bright future without cancer. There are still many ongoing studies in the field of cancer research that offer hope in the global fight against it. By deepening our understanding of metastasis, we can work towards earlier detection, prevention and more effective treatments to offer improved outcomes worldwide.
Metastasis is the spread of cancer cells from a primary tumour to other parts of the body and has a big impact on treatment and patient survival. The process of metastasis involves several complex steps to establish secondary tumours. Both molecular and micro-environmental factors influence metastatic behaviour. Without the right conditions, the cancer cells would not be able to survive and grow. Early detection and prevention are key to managing metastatic disease. Earlier diagnosis and limited metastatic spread mean more treatment options and improved prognosis. New research surrounding targeted therapies for metastasis provides hope for better treatment outcomes in the future.
What is metastasis in simple terms?
Metastasis is the spread of cancer from one area of the body to another.
What stage of cancer is metastasis?
Metastasis occurs in stage 4, which is the most advanced stage.
Does metastasis mean cancer?
The presence of metastasis indicates that cancer is present.
What are the 3 types of metastases?
The 3 main types of metastasis are local, regional and distant metastasis; these all refer to the location or the spread from the primary tumour.
- Park M, Kim D, Ko S, Kim A, Mo K, Yoon H. Breast Cancer Metastasis: Mechanisms and Therapeutic Implications. Vol. 23, International Journal of Molecular Sciences. MDPI; 2022. Available from: https://pubmed.ncbi.nlm.nih.gov/35743249/
- Castaneda M, den Hollander P, Kuburich NA, Rosen JM, Mani SA. Mechanisms of cancer metastasis. Semin Cancer Biol. 2022 Dec;87:17-31. Available from: https://pubmed.ncbi.nlm.nih.gov/36354098/
- Lyden D, Ghajar CM, Correia AL, Aguirre-Ghiso JA, Cai S, Rescigno M, et al. Metastasis. Vol. 40, Cancer Cell. Cell Press; 2022. p. 787–91. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9924435/
- Joyce JA, Pollard JW. Microenvironmental regulation of metastasis. Vol. 9, Nature Reviews Cancer. 2009. p. 239–52. Available from: https://pubmed.ncbi.nlm.nih.gov/19279573/
- Welch DR, Hurst DR. Defining the Hallmarks of Metastasis. Vol. 79, Cancer Research. American Association for Cancer Research Inc.; 2019. p. 3011–27. Available from: https://pubmed.ncbi.nlm.nih.gov/31053634/
- Pisani P, Airoldi M, Allais A, Valletti PA, Battista M, Benazzo M, et al. Metastatic disease in head & neck oncology. Acta Otorhinolaryngologica Italica. 2020;40(2):S1–86. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263073/
- Guan X. Cancer metastases: Challenges and opportunities. Vol. 5, Acta Pharmaceutica Sinica B. Chinese Academy of Medical Sciences; 2015. p. 402–18. Available from: https://pubmed.ncbi.nlm.nih.gov/26579471/
- Debela DT, Muzazu SGY, Heraro KD, Ndalama MT, Mesele BW, Haile DC, et al. New approaches and procedures for cancer treatment: Current perspectives. Vol. 9, SAGE Open Medicine. SAGE Publications Ltd; 2021. Available from: https://pubmed.ncbi.nlm.nih.gov/34408877/
- Palumbo MO, Kavan P, Miller WH, Panasci L, Assouline S, Johnson N, et al. Systemic cancer therapy: Achievements and challenges that lie ahead. Vol. 4 MAY, Frontiers in Pharmacology. 2013. Available from: https://pubmed.ncbi.nlm.nih.gov/23675348/
- Esposito M, Ganesan S, Kang Y. Emerging strategies for treating metastasis. Vol. 2, Nature Cancer. Nature Research; 2021. p. 258–70. Available from: https://pubmed.ncbi.nlm.nih.gov/33899000/
- Mokhtari RB, Homayouni TS, Baluch N, Morgatskaya E, Kumar S, Das B, et al. Combination therapy in combating cancer. Oncotarget [Internet]. 2017 Jun 6 [cited 2023 Sep 20];8(23):38022–43. Available from: https://pubmed.ncbi.nlm.nih.gov/28410237/
- Crosby D, Bhatia S, Brindle KM, Coussens LM, Dive C, Emberton M, et al. Early detection of cancer. Science. 2022 Mar 18;375(6586):eaay9040. Available from: https://pubmed.ncbi.nlm.nih.gov/35298272/
- Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, et al. Cancer is a preventable disease that requires major lifestyle changes. Vol. 25, Pharmaceutical Research. Springer New York LLC; 2008. p. 2097–116. Available from: https://pubmed.ncbi.nlm.nih.gov/18626751/