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CORR Insights®: Elevated Expression of Transforming Acidic Coiled-Coil Containing Protein 3 (TACC3) Is Associated With a Poor Prognosis in Osteosarcoma

Conventional primary osteosarcoma is the most-common malignant bone tumor. As an aggressive neoplasm, it often affects young individuals, potentially taking years off patients’ lives [6]. Standard chemotherapy and sophisticated surgical techniques have led to an improved prognosis, enabling complete tumor resection with wide margins and limb salvage in most patients. However, patients with limited response to chemotherapy or with distant metastases still have a poor prognosis [5]. In the age of molecular medicine and precision oncology, the standard chemotherapy regimen for osteosarcoma seems somewhat outdated. Our classification systems may need to be revised as well, particularly a few histomorphological subtypes under the WHO classification system (such as osteoblastic or chondroblastic osteosarcoma), which seem to have no prognostic or therapeutic discriminative value [6]. This contrasts with many other tumors that now are classified using molecular properties such as microsatellite instability (colon carcinoma), isocitrate dehydrogenase mutation (gliomas), human epidermal growth factor receptor 2 amplification (breast carcinoma) and, most of all, leukemias. Still, osteosarcoma has been investigated extensively for genetic alterations and numerous mutations have been found [3]. Osteosarcoma shows an unusually high level of chromosomal aberrations, similar to pancreatic carcinoma. But a new class of immune checkpoint inhibitors like nivolumab has scarcely been examined and has shown only a limited effect against osteosarcoma [4]. Transforming Acidic Coiled-Coil Protein 3 (TACC3) has gained attention since it is associated with esophageal, hepatocellular, gastric carcinoma, and soft-tissue sarcomas. An in-vitro study found a correlation between TACC3 and osteosarcoma cell growth and migration [8], and now Matsuda and colleagues [2], in the current study, demonstrate the association of elevated TACC3 immunohistochemical expression with poor prognosis in patients with osteosarcoma. TACC3 expression might not only be a prognostic discriminator, but also a worthwhile target for personalized therapy, since another recent report found a small-molecule TACC3 inhibitor called KHS101 to be effective against breast cancer cells [1].