ABSTRACT
BAG3, also known as BIS and CAIR-1, interacts with Hsp70 via its BAG domain and with other molecules through its WW domain, PXXP repeats and IPV motifs. BAG3 can participate in major cellular pathways including apoptosis, autophagy, cytoskeleton structure, and motility by regulating the expression, location, and activity of its chaperone proteins. As a multifunctional protein, BAG3 is highly expressed in skeletal muscle, cardiomyocytes and multiple tumors, and its intracellular expression can be stimulated by stress. The functions and mechanisms of BAG3 in hematological malignancies have recently been a topic of interest. BAG3 has been confirmed to be involved in the development and chemoresistance of hematological malignancies and to act as a prognostic indicator. Modulation of BAG3 and its corresponding proteins has thus emerged as a promising therapeutic and experimental target. In this review, we consider the characteristics of BAG3 in hematological malignancies as a reference for further clinical and fundamental investigations.
Subject(s)
Adaptor Proteins, Signal Transducing , Apoptosis Regulatory Proteins , Hematologic Neoplasms , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Autophagy/physiology , HSP70 Heat-Shock Proteins/metabolism , Hematologic Neoplasms/drug therapy , Hematologic Neoplasms/genetics , HumansABSTRACT
BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are recommended for patients with non-small cell lung cancer with EGFR mutations. However, acquired resistance to EGFR-TKIs seems inevitable and the mechanism of drug resistance has not been fully defined. There is no effective treatment for patients with advanced lung adenocarcinoma who are resistant to TKIs owing to pathologic type conversion. CASE PRESENTATION: We report a patient who was initially diagnosed with lung adenocarcinoma. At first, she was sensitive to the first-generation TKI icotinib. After 17 months of treatment, the patient acquired resistance to icotinib. Moreover, after tumor resection, immunohistochemical analysis showed pathologic change from adenocarcinoma to adenosquamous carcinoma, and next-generation sequencing technology discovered EGFR exon19 p.745-750 del, exon20 p.T790M, and KMT2C exon 18 p.R973G mutations. After video-assisted tumor resection, the patient is receiving osimertinib (AZD 9291). Current overall survival is 60 months. CONCLUSIONS: Surgical intervention may prolong survival time in patients with acquired TKI resistance, especially when there is no evidence of metastasis.
