Colorectal cancer (CRC) is one of the most frequent and lethal cancer types worldwide. While surgery with chemotherapy and radiotherapy remains the only curative approach for localized CRC, for metastatic disease the therapeutic landscape has significantly evolved over the last years. Development and approval of novel targeted therapies, such as monoclonal antibodies against EGFR and VEGF, have significantly increased the median survival of patients with metastatic disease, with some trials reporting a benefit over 40 months. Increasing accessibility of high throughput sequencing has unraveled several new therapeutic targets. Actionable alterations, such as HER2 overexpression, BRAF mutations, and NTRK fusions, are currently available in metastatic disease, providing significant therapeutic opportunities for these patients, while new emerging agents, as immune checkpoint inhibitors, promise better treatment options in the near future. In this chapter, an overview of established and future CRC targeted therapies in the clinical setting is provided, as well as their mechanism of action, limitations, and future applicability.
Part of the book: Colorectal Cancer
Giant cell tumor of bone (GCTB) is mostly a benign disease of the bone, although with high local recurrence rate and potential for metastatic spread, namely to the lungs. It is also a locally aggressive tumor, associated with severe morbidity and functional impairment due to bone destruction. Treatment is therefore required and should be offered at an early stage to allow complete resection, minimizing functional sequelae and local recurrence. Surgical resection is the mainstay of treatment, often followed by intralesional adjuvant therapy. GCTB has a particular biology, in which RANKL represents a key factor in tumor pathogenesis, thus making this molecule a valuable therapeutic target. Monthly administration of denosumab, a fully human monoclonal antibody directed against RANKL, has been studied in several clinical trials and shown a high rate of local control with favorable safety profile. In this chapter, current medical management, ongoing studies, and future directions in GCTB will be discussed.
Part of the book: Recent Advances in Bone Tumours and Osteoarthritis