Sarcomas: A Low-Incidence Malignancy with Limited Treatment Options

Figure 1. Types of bone and soft tissue sarcomas arising in various areas of the human body. Diagram from MedStar Health (2025).

We often hear about lymphomas, carcinomas, and types of leukaemia, but sarcomas are often a forgotten category of cancer, and are unknown to many people.

This is partly due to their rarity. Sarcomas, including bone and soft tissue, comprise less than 2% of cases diagnosed each year in the UK, and closer to 1% in the USA, compared to carcinomas, which comprise about 90% of all cases (Cooper, 2000). In addition, 12-15% of childhood cancers are sarcomas, however due to their vague symptoms and the rarity of the disease, they can often go misdiagnosed (Lim et al., 2015).

This rarity unfortunately translates to underfunding and insufficient study in this area of oncology, which then makes finding new treatments even more challenging without a wide prior database of information on this cancer, and what subtypes of sarcomas can respond to different treatments. This disproportionately affects young children, who are more at risk of developing the disease, and can tragically cut their lives short before they've even begun.

What are sarcomas?

These cancers arise from a type of tissue called mesenchymal tissue, including bone, connective tissue, fat and muscle. "Mesenchymal" refers to the tissue that comes from the mesoderm, a group of cells in a developing embryo which go on to form important connective tissues in the foetus through differentiation (Bianco et al., 2013).

Compared to the more common carcinomas, sarcomas are so rare because the human body consists of much more epithelial tissue that is frequently undergoing cell turnover, giving the opportunity for carcinomas such as in breast or lung tissue to arise. Connective and bone tissue has a lower rate of cell division, and is often not as exposed to factors that could damage the cells and cause cancer, such as exposure of epithelial cells in the airway to smoke.

In sarcomas, there is often not a clear reason as to what causes these rare cancers, meaning there is not a general public guideline as to how to prevent them. "Smoking cessation will help prevent onset of lung cancer" is something frequently heard, meaning cancers like this are well known because of their publicity. Sarcomas do not get the same treatment.

Why do they develop?

Sarcomas often develop in children because as they grow, their connective tissues are undergoing more frequent cell division, giving more opportunities for cancer to arise from dysregulated cell division. Sarcoma development does not have to arise from inherited genetic conditions; rapid growth spurts in children are enough for multiple mutations and therefore cancer to develop.

But inherited conditions do play a big role in many cancers. Li-Fraumeni syndrome is an inherited condition where a mutation in the TP53 tumour suppressor gene is passed to children. This means every cell in their body starts with only one functional copy of the gene. It then only takes one additional, random mutation in that remaining copy for the crucial p53 protein to stop carrying out its role in DNA repair and programmed cell death. This allows cancer to develop a lot easier than in individuals without this mutation, including bone and soft tissue sarcomas (Swaminathan, M. et al.,2019).

Current treatments for sarcomas

Sarcomas are difficult to treat as their location is often concealed, and often have aggressive and resistant properties that vary between subtypes. Their low-incidence rate means that researchers have less cases to work and study with and it is a lot harder to find treatments that are effective if large-scale clinical trials cannot be carried out.

Surgery is often a first step in tumours that haven't spread, to take away the cancerous cells so that the cancer is removed from the body, however even a couple of cells left behind can cause another tumour to grow, so this is a very precise procedure that may take away healthy tissue also to ensure full removal. Limbs are rarely amputated if a sarcoma is in a limb, but can be if the sarcoma appears multiple times or the sarcoma is impossible to remove.

Radiation is often used in combination with surgery, to shrink the tumour or remove any cells left behind. It can also be used if the sarcoma cannot be surgically removed (Cancer Research UK, 2024).

Chemotherapy varies in effectiveness for sarcomas. In many places, it is not commonly used as the response rates are often not favourable. Some people may be offered chemotherapy for sarcomas such as doxorubicin, which helps break cellular DNA so cancer cells die (Kciuk et al., 2023). But the response rates differ hugely between different patients, different chemotherapies regimes and different sarcoma subtypes and there is no guarantee chemotherapy will be worth the damage it causes to the patient.

Targeted treatment is an evolving area in the treatment of these difficult cancers, but need much more research into what is effective in this area, especially since many chemotherapies are inadequate in treatment. Imatinib is a targeted drug that has shown promise for shrinking gastrointestinal sarcomas, but does come with a chance of resistance to the drug (Tan et al., 2013).

Sarcomas are a diverse and highly adaptive group of cancers with many subtypes, and often are aggressive, resistant to chemotherapy, and can spread fast. Their rarity contrasts with the more common carcinomas and other cancer types, making their treatment options more limited as they are not as well-established, as there are less cases worldwide to be studied. The future of care for sarcomas may lie in targeted therapies, or future immunotherapies, granted we can make these tumours respond more to the action of our own immune systems, as many chemotherapies create a varied response. These kind of treatments pave the way for precision oncology, where a patient's sarcoma will be treated based on their genetic make-up, instead of a broad, general approach, which are ineffective for many patients. This rare cancer type requires further studying, further research and clinical trials in order to fully characterise the genetic mechanisms behind each and every subtype, to find new areas and new treatments that minimise harmful side effects but maximise the demise of the sarcoma, for new life-saving therapies.

References:

Bianco, P. et al. (2013) 'The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine', Nature Medicine, 19(1), pp. 35–42.

Cancer Research UK (2024) 'Treatment options | Soft tissue sarcoma', [online] Available at: https://www.cancerresearchuk.org/about-cancer/soft-tissue-sarcoma/treatment/treatment-options-for-soft-tissue-sarcoma (Accessed: 1 August 2025).

Cooper, G.M., 2000. The Cell: A Molecular Approach. 2nd edn. Sunderland (MA): Sinauer Associates. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9963/ (Accessed 1 August 2025).

Kciuk, M. et al. (2023) 'Doxorubicin-An Agent with Multiple Mechanisms of Anticancer Activity', Cells, 12(4), p. 659.

Lim, S.M. et al., 2015. Incidence and Survival of Pediatric Soft Tissue Sarcomas: Comparison between Adults and Children. Cancer Research and Treatment, 47(1), pp.9–17.

Medstar Health (2025). Soft Tissue Sarcomas. Available at: https://www.medstarhealth.org/services/soft-tissue-sarcomas (Accessed: 1 August 2025).

Swaminathan, M. et al. (2019) 'Hematologic malignancies and Li-Fraumeni syndrome', Cold Spring Harbor Molecular Case Studies, 5(1), p. a003210.

Tan, C., Yang, J., Crowe, P., & Goldstein, D. (2013). Targeted therapy in soft tissue sarcoma—a novel direction in therapeutics. Chinese Clinical Oncology, 2(3), 22.

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