RESUMO
B-Cell Lymphoma 2 (BCL-2), c-MYC and related proteins are arguably amongst the most widely studied in all of biology. Every year there are thousands of papers reporting on different aspects of their biochemistry, cellular and physiological mechanisms and functions. This plethora of literature can be attributed to both proteins playing essential roles in the normal functioning of a cell, and by extension a whole organism, but also due to their central role in disease, most notably, cancer. Many cancers arise due to genetic lesions resulting in deregulation of both proteins, and indeed the development and survival of tumours is often dependent on co-operativity between these protein families. In this review we will discuss the individual roles of both proteins in cancer, describe cancers where co-operativity between them has been well-characterised and finally, some strategies to target these proteins therapeutically.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Compostos de Anilina/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Compostos de Bifenilo/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Ensaios Clínicos como Assunto , Regulação Neoplásica da Expressão Gênica , Humanos , Morfolinos/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Nitrofenóis/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Piperazinas/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/uso terapêutico , Rituximab/uso terapêutico , Transdução de Sinais , Sulfonamidas/uso terapêuticoRESUMO
Idronoxil has been the subject of more than 50 peer-reviewed publications over the last two decades. This isoflavone is an intriguing regulator of multiple signal transduction pathways, capable of causing a range of biological effects, including cell cycle arrest, apoptosis, an ability to stimulate the immune system, and inhibition of angiogenesis. These multifaceted actions suggest that idronoxil has the potential to synergize with, or complement, a wide range of cancer therapies. Whilst clinically tested in the past, idronoxil's journey was discontinued as a result of its low bioavailability in humans when administered either intravenously or orally, though strategies to overcome this issue are currently being explored. Here, we summarize the current literature regarding the key cellular targets of idronoxil and the mechanisms by which idronoxil exerts its anticancer effects, laying a new foundation toward giving this unique molecule a second chance of contributing to the future of cancer treatment.