With the ever-expanding therapeutic indications and ongoing clinical trials with Poly(adenosine diphosphate-ribose) Polymerase (PARP) inhibitors, it is of outmost importance to stop and rethink what we know and still do not know concerning one of the major revolutions in target therapies in the last decades. Indeed, many PARP inhibitors (PARPi) are able to bind multiple targets, with a plethora of potential interactions with cancer cell signaling, metabolism and the tumor microenvironment (TME). These interactions can mediate both response and resistance to PARPi, but also represent an opportunity for sequential and/or combinatorial therapies. Here we advocate a "look before you leap" approach in reviewing available clinical and preclinical evidence concerning PARPi, delving into this complex entanglement, trying to unravel the potential for innovative therapeutic strategies revolving on PARP inhibition.

中文翻译：

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深入研究从长凳到床头再到背部的PARP抑制作用。

随着聚腺苷二磷酸核糖核糖聚合酶（PARP）抑制剂的治疗适应症不断扩展和临床试验的进行，停止和重新思考我们对靶标的一项重大革命所知道和仍不知道的事情极为重要。最近几十年的疗法。实际上，许多PARP抑制剂（PARPi）能够结合多个靶标，并且与癌细胞的信号传导，代谢和肿瘤微环境（TME）有很多潜在的相互作用。这些相互作用可以介导对PARPi的应答和抗性，但也代表了序贯和/或组合疗法的机会。在这里，我们提倡“三思而后行”的方法，以审查有关PARPi的可用临床和临床前证据，研究这种复杂的纠缠，