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Bone cancer

Pathology and emerging therapeutics

Introduction: what is bone cancer?


Primary bone cancer can originate in any bone. However, most cases develop in the long bones of the legs or upper arms. Each year, approximately 550 new cases are diagnosed in the United Kingdom.

 

Primary bone cancer is distinct from secondary bone cancer, which occurs when cancer spreads to the bones from another region of the body. The focus of this article is on primary bone cancer. There are several types of bone cancer: osteosarcoma, Ewing sarcoma, and chondrosarcoma.

 

Osteosarcoma originates in the osteoblasts that form bone. It is most common in children and teens, with the majority of cases occurring between the ages of 10 and 30.

 

Ewing (pronounced as YOO-ing) sarcoma develops in bones or the soft tissues around the bones. Like osteosarcoma, this cancer type is more common in children and teenagers.

 

Chondrosarcoma occurs in the chondrocytes that form the cartilage. Chondrosarcoma is most common in adults between the ages of 30 and 70 and is rare in the under-21 age group.

 

Causes of bone cancer include genetic factors such as inherited mutations and syndromes, and environmental factors such as previous radiation exposure. Treatment will often depend on the type of bone cancer, as the specific pathogenesis of each case is unknown.


What is the standard treatment for bone cancer?


Most patients are treated with a combination of surgical excision, chemotherapy, and radiation therapy.

 

Surgical excision is employed to remove the cancerous bone. Typically, it is possible to repair or replace the bone, although amputation is sometimes required.

 

Chemotherapy involves using powerful chemicals to kill rapidly growing cells in the body. It is widely used for osteosarcoma and Ewing sarcoma but less commonly used for chondrosarcomas.

 

Radiation therapy (also termed radiotherapy) uses high doses of radiation to damage the DNA of cancer cells, leading to the killing of cancer cells or slowed growth.

 

Six out of every ten individuals with bone cancer will survive for at least five years after their diagnosis, and many of these will be completely cured.

 

However, these treatments have limitations in terms of effectiveness and  side effects.

 

The limitation of surgical excision is the inability to eradicate microscopic cancer cells around the edges of the tumour. Additionally, the patient must be able to withstand the surgery and anaesthesia.

 

Chemotherapy can harm the bone marrow, which produces new blood cells, leading to low blood cell counts and an increased risk of infection due to a shortage of white blood cells.

 

Moreover, radiation therapy uses high doses of radiation, resulting in the damage of nearby healthy tissues such as nerves and blood vessels.

 

Taken together, this underscores the need for a therapeutic approach that is non-invasive, bone cancer-specific, and with limited side effects.

 

miR-140 and tRF-GlyTCC


Dr Darrell Green and colleagues investigated the role of small RNAs (sRNAs) in bone cancer and its progression.

 

Through the analysis of patient chondrosarcoma samples, the researchers identified two sRNA candidates associated with overall patient survival: miR-140 and tRF-GlyTCC. MiR-140 was suggested to inhibit RUNX2, a gene upregulated in high-grade tumours. Simultaneously, tRF-GlyTCC was demonstrated to inhibit RUNX2 expression by displacing YBX1, a multifunctional protein with various roles in cellular processes.

 

Interestingly, the researchers found that tRF-GlyTCC was attenuated during chondrosarcoma progression, indicating its potential involvement in disease advancement.

 

Furthermore, since RUNX2 has been shown to drive bone cancer progression, the identified miR-140 and tRF-GlyTCC present themselves as promising therapeutic targets.

 

CADD522


Dr Darrell Green and colleagues subsequently investigated the impact of a novel therapeutic agent, CADD522, designed to target RUNX2.

 

In vitro experiments have revealed that CADD522 reduced proliferation in chondrosarcoma and osteosarcoma. However, a bimodal effect was observed in Ewing sarcoma, indicating that lower levels of CADD522 promoted sarcoma proliferation, whereas higher levels of the same drug suppressed proliferation.

 

In mouse models treated with CADD522, there was a significant reduction in cancer volumes observed in both osteosarcoma and Ewing sarcoma.


Take-home message


The results described here contribute to understanding the molecular mechanisms involved in bone cancer. They highlight the anti-proliferative and anti-tumoral effects of CADD522 in treating osteosarcoma and Ewing sarcoma. Further research is necessary to fully elucidate the specific molecular mechanism of CADD522 in bone cancer and to identify potential side effects.

 


By Favour Felix-Ilemhenbhio


Related article: Secondary bone cancer

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