RESUMEN
INTRODUCTION: The significant challenge posed by cancer to human healthcare has led to the exploration of new approaches to combat it. Synthetic lethality (SL) is one such emerging area in the development of novel anticancer therapies. SL can be described as lethality (cell death) resulting from the combination of the two mutations, wherein the mutation in either of the two codependent genes in normal or cancer cells is viable. This concept is specifically being exploited in cancer research for selectively targeting specific tumor cells. AREAS COVERED: In this review, the authors summarize studies of SL-based novel anticancer therapies. The review highlights some of the selected advances in DNA damage response pathway-related SL pairs, particularly poly (ADP-ribose) polymerase (PARP) and SL pairs involved in mitochondrial death signaling pathways published in the last 3 years. EXPERT OPINION: Most of the currently used chemotherapeutic agents will destroy cells irrespective of whether they are cancer cells or fast growing normal cells; but SL is one of the approaches being developed with potential as a selective cancer therapy. PARP inhibitors, such as olaparib, are useful in BRCA mutated cancer cells and are also used in combination with other drug to enhance their efficacy. Research on PARP inhibitors is progressing at a good pace but there are still some significant challenges that must be addressed.
Asunto(s)
Antineoplásicos/farmacología , Diseño de Fármacos , Neoplasias/tratamiento farmacológico , Muerte Celular/efectos de los fármacos , Humanos , Terapia Molecular Dirigida , Mutación , Neoplasias/genética , Neoplasias/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacologíaRESUMEN
INTRODUCTION: Apoptosis is an important and extensively studied pathway of programmed cell death, which is central to different physiological processes. Varied pathological implications, not limited to cancer and neurodegenerative diseases, occur if a slight dysfunction happens in the intricate apoptotic pathway. Therefore, it has become one of the prime molecular target for drug discovery and development particularly for diseases like cancer. AREAS COVERED: As a promising drug target in the development of cancer chemotherapeutics, apoptosis has received extensive attention and hundreds of thousands of reports have been published. In the present review, the patents filed/published on apoptosis-inducing agents during the period of 2010 - 2013 have been compiled and discussed. EXPERT OPINION: Most of the chemotherapeutics employed in cancer treatment leads to suppression of tumor via cell death irrespective of the mechanism of action or molecular target. No effective drug has emerged from the direct activation/inhibition of apoptotic regulatory proteins and of late some potential drugs, such as oblimersen, navitoclax, etc., targeting Bcl-2 family of proteins are under clinical trials. However, most of these molecules lacks efficacy accompanied with significant toxicity and resistance. Concerted efforts are required such as combination therapies and identification of newer selective inhibitor to overcome these limitations.