The Role of Bcl-xL Protein Research in Veterinary Oncology

Abstract

Due to their significant impact on human and animal health, cancer diseases are an area of considerable concern for both human and veterinary medicine. Research on the cancer pathogenesis in companion animals, such as dogs, allows not only for improving canine cancer treatment, but also for translating the results into human oncology. Disruption of apoptosis in tumor-transformed cells is a well-known mechanism leading to the development of cancer. One of the main factors involved in this process are proteins belonging to the B-cell lymphoma 2 (Bcl-2) family, and the imbalance between pro-apoptotic and anti-apoptotic members of this family contributes to the development of cancer. Studies on the function of these proteins, including B-cell lymphoma-extra large (Bcl-xL), have also been intensively conducted in companion animals. The Bcl-xL gene was sequenced and found to share over 99% homology with the human protein. Research showed that the Bcl-2 family plays the same role in human and canine cells, and data from studies in dogs are fully translatable to other species, including humans. The role of this protein family in cancer development was also confirmed. The article presents the current state of knowledge on the importance of the Bcl-xL protein in veterinary oncology.

Case report: BCL-2 and CD31 immunoexpression related to clinical and histopathological evaluation of renal dysplasia in a Welsh Corgi Puppy

“…Second, the antibodies used in this study were specific for human BCL-2 and CD31 (PECAM-1) due to the limitation of commercial antibodies against dogs. However, there is a high homologous amino acid sequence (more than 90%) of these proteins between humans and dogs ( 34 , 35 ). The finding on these antibodies therefore could be suitable for dogs.…”

PROTACs: A novel strategy for cancer drug discovery and development

“…Inhibition of BCL‐X L protein has been widely recognized as a promising strategy for cancer therapy, and several representative anticancer drug candidates in the BCL‐X L inhibitor class have been produced. 383 Although these inhibitors are effective in the treatment of certain hematological malignancies such as CLL and AML, BCL‐X L inhibitors still present significant challenges, such as developed resistance and dose limitations that limit their clinical efficacy. 384 Thus, there is an urgent need to develop a new approach to the development of BCL‐X L targeted drugs, and PROTAC technology comes to the stage.…”

DNA damage response proteins in canine cancer as potential research targets in comparative oncology

“…An additional advantage of the dog model is the fact that in both species, humans and dogs, development of tumours is spontaneous, showing higher incidence with age. Heterogeneous course of disease in different patients with an analogous metastatic behaviour, comparable response to antineoplastic therapies, and alteration in DDR pathway are further similarities 28,63,64 . Additionally, over 360 genetic disorders related to cancer were described in dogs, and this constitutes the largest set of natural genetic disorders in a non‐human species 65 .…”

“…Heterogeneous course of disease in different patients with an analogous metastatic behaviour, comparable response to antineoplastic therapies, and alteration in DDR pathway are further similarities. 28 , 63 , 64 Additionally, over 360 genetic disorders related to cancer were described in dogs, and this constitutes the largest set of natural genetic disorders in a non‐human species. 65 These findings clearly justify the need for close cooperation between veterinary and human oncologists in the field of genetic instability and particularly DDR disorders.…”