RESUMEN
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.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-myc/genética , Compuestos de Anilina/uso terapéutico , Apoptosis/efectos de los fármacos , Apoptosis/genética , Compuestos de Bifenilo/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Ensayos Clínicos como Asunto , Regulación Neoplásica de la Expresión Génica , Humanos , Morfolinos/uso terapéutico , Neoplasias/metabolismo , Neoplasias/patología , Nitrofenoles/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-myc/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas Proto-Oncogénicas c-myc/uso terapéutico , Rituximab/uso terapéutico , Transducción de Señal , Sulfonamidas/uso terapéuticoRESUMEN
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.