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Opinion - Journal of Molecular Pathophysiology (2023)
Dysregulated Signaling Pathways in Tumor Progression and Genomic Instability
Ines Strnad*Ines Strnad, Department of Pathology, University of Indonesia, Jakarta, Indonesia, Email: Strnad2000@yahoo.com
Received: 22-Sep-2023, Manuscript No. JMOLPAT-23-119192; Editor assigned: 25-Sep-2023, Pre QC No. JMOLPAT-23-119192 (PQ); Reviewed: 10-Oct-2023, QC No. JMOLPAT-23-119192; Revised: 17-Oct-2023, Manuscript No. JMOLPAT-23-119192 (R); Published: 24-Oct-2023
About the Study
Osteosarcoma is a rare and aggressive form of bone cancer. This malignant neoplasm is primarily characterized by the uncontrolled growth of osteoid tissue, a primitive bone-forming tissue, and it commonly affects the long bones, such as the arms and legs. Understanding the pathology of osteosarcoma is crucial for early diagnosis, effective treatment, and improved patient outcomes [1]. The exact cause of osteosarcoma remains largely unknown, but it is believed to involve a combination of genetic and environmental factors. Some hereditary conditions, such as Li-Fraumeni syndrome and hereditary retinoblastoma, are known to increase the risk of osteosarcoma. Osteosarcoma is one type of bone tumor that is more common in people with these genetic mutations. Paget's disease of bone is a rare condition that can lead to the development of osteosarcoma in affected bones.
Osteosarcoma is most commonly diagnosed in adolescents and young adults, with a slight male predominance. There is some evidence to suggest that certain racial and ethnic groups may be at a higher risk for osteosarcoma [2]. Exposure to certain chemicals, such as beryllium, has been linked to an increased risk of osteosarcoma. Osteosarcoma is a diverse group of tumors that can be classified based on various criteria. Conventional Osteosarcoma is the most common form, accounting for approximately 75% of cases. It is further divided into osteoblastic, chondroblastic, and fibroblastic subtypes based on the predominant type of tissue produced.
Telangiectatic osteosarcoma variant is characterized by large, blood-filled cavities within the tumor. Small cell osteosarcoma is a rare subtype is composed of small, round cells and is associated with a poorer prognosis. The low-grade Osteosarcoma variant is less aggressive and progresses more slowly than other forms. Histopathological examination is essential for confirming the diagnosis of osteosarcoma. The hallmark of osteosarcoma is the production of osteoid tissue, which is a mineralized bone matrix [3]. Osteosarcoma cells produce irregular osteoid tissue, which appears as eosinophilic (pink) material on histological slides. This osteoid is often arranged randomly and lacks the organized structure seen in normal bone tissue. Osteosarcoma is composed of a mixture of malignant cells, including osteoblast-like cells, spindle-shaped cells, and pleomorphic cells. Increased mitotic activity is commonly observed, indicating the high rate of cell proliferation in osteosarcoma. Many osteosarcomas contain areas of necrosis, which can appear as eosinophilic material with loss of cellular detail. Osteosarcoma is characterized by its invasive nature, with tumor cells infiltrating the surrounding bone tissue [4].
The fundamental mechanisms of osteosarcoma have been clarified by developments in genetic and molecular research. Alterations in the TP53 gene are common in osteosarcoma and are associated with increased genetic instability and tumor progression. Inactivation of the RB1 gene is another frequent genetic event in osteosarcoma. Loss of RB1 function leads to uncontrolled cell division. Dysregulation of various signaling pathways, such as the Wnt and Hedgehog pathways, has been implicated in osteosarcoma pathogenesis [5]. Osteosarcoma often exhibits a high degree of genomic instability, which contributes to its aggressive behavior.
Aberrant epigenetic modifications, including DNA methylation and histone modifications play a role in gene expression changes observed in osteosarcoma. The clinical presentation of osteosarcoma varies depending on the location and extent of the tumor [6]. Osteosarcoma often presents with localized, persistent bone pain, which may initially be attributed to injury or growing pains. Swelling or a mass at the site of the tumor is a common physical finding. In cases where the tumor affects joints, there may be a restriction in movement. Osteosarcoma can weaken the bone, leading to an increased risk of fractures, sometimes even occurring with minimal trauma. In advanced cases, patients may experience systemic symptoms, such as fatigue, weight loss, and fever [7]. Diagnosis typically involves a combination of imaging studies, such as X-rays, CT scans, MRI, and bone scans, to visualize the tumor and assess its extent. A biopsy is essential to confirm the diagnosis and determine the histological subtype of the tumor. A core needle biopsy or open surgical biopsy may be performed, with the latter being preferred to obtain an adequate tissue sample. The management of osteosarcoma is multidisciplinary and involves a combination of surgery, chemotherapy, and sometimes, radiation therapy. The choice of treatment depends on factors such as the stage of the disease, location of the tumor, and the presence of metastases [8].
Chemotherapy plays a crucial role in the management of osteosarcoma, both before and after surgery. Neoadjuvant chemotherapy helps shrink the tumor and makes surgical resection more feasible. Adjuvant chemotherapy aims to eradicate any remaining cancer cells and reduce the risk of recurrence. Commonly used chemotherapy agents include doxorubicin, cisplatin, methotrexate, and ifosfamide [9]. In certain circumstances, such as when surgery is not an option to remove the tumor or when pain management is necessary due to metastatic disease, radiation therapy for osteosarcoma may be considered as a primary treatment. The prognosis for osteosarcoma largely depends on various factors, including the stage of the disease, the response to treatment, and the histological subtype. Overall, osteosarcoma has a relatively better prognosis for localized disease than for cases with metastases [10]. Regular follow-up care is crucial for monitoring the patient's condition and detecting any signs of recurrence. Follow-up visits typically involve physical examinations, imaging studies, and blood tests to assess the patient's response to treatment and to detect any potential recurrence of the disease.
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