Review Question - QID 220360

Several therapies, including tyrosine kinase inhibitors, have been developed to target specific molecular alterations found in cancer cells' signaling pathways. Tyrosine kinase inhibitors and other chemotherapy agents induce apoptosis in target cancer cells (Answer 1).

Despite extensive research, the long-term survival rate of non-metastatic osteosarcoma has stagnated at less than 60% since the 1980s. This has led to the development of targeted therapies that focus on unique weaknesses in neoplastic cells. Tyrosine kinase inhibitors are currently being used for cancer chemotherapy in diagnoses such as chronic myelogenous leukemia, metastatic breast cancer, and osteosarcoma. Tyrosine kinase receptors are a family of receptors that naturally occur in nature and are often over-expressed in neoplastic cancer cells. Each has a tyrosine kinase domain (which phosphorylates proteins on tyrosine residues), a hormone-binding domain, and a carboxyl terminal segment with multiple tyrosines for autophosphorylation.

Shawver et al. published a review article regarding tyrosine kinase inhibitors in cancer therapy. The authors highlight the breakthroughs in breast cancer research that led to Herceptin, the first targeted anti-kinase therapeutic approved for cancer therapy. Although additional research is needed to elucidate the complete treatment pathways, tyrosine kinase inhibitors work by inducing apoptosis of tumor cells.

Assi et al. published a review article regarding tyrosine kinase inhibitors in osteosarcoma. Management of osteosarcoma typically involves neoadjuvant chemotherapy (including methotrexate, doxorubicin, and cisplatin), surgical resection, and adjuvant chemotherapy. Tyrosine kinase inhibitors have been trialed in treatment and are more effective when combined with other systemic therapies. The authors recommend randomized controlled trials with appropriate targeting based on biomarkers to understand this therapeutic option further.

Figure A shows an AP plain film of a skeletally mature individual with a lucent lesion in the metaphysis and distal diaphysis of the femur. Figure B shows a coronal MRI of a distal femur that shows lesion extension beyond the cortex with edema in the adjacent soft tissue.

Incorrect Answers:
Answer 2: Autophagy is a programmed nonapoptotic cell death pathway mediated by nucleation of the ULK1 complex.
Answer 3: Necrosis is nonprogrammed, nonapoptotic cell death resulting from calcium influx into the cell.
Answer 4: Necroptosis is programmed nonapoptotic cell death in which the membrane ruptures.
Answer 5: Pyroptosis is programmed nonapoptotic cell death that utilizes caspase-1-mediated pore formation.