Background: The EGFR is overexpressed in numerous cancers. So, it becomes one of the most favorable drug targets. Single-acting EGFR inhibitors on prolong use induce resistance and side effects. Inhibition of EGFR and/or its interacting proteins by dual/combined/multitargeted therapies can deliver more efficacious drugs with less or no resistance.

Objective: The review delves deeper to cover the aspects of EGFR mediated endocytosis, leading to its trafficking, internalization, and crosstalk(s) with HDACs.

Methods and Results: This review is put forth to congregate relevant literature evidenced on EGFR, its impact on cancer prognosis, inhibitors, and its trafficking regulation by acetylation along with the current strategies involved in targeting these proteins (EGFR and HDACs) successfully by involving dual/hybrid/combination chemotherapy.

Conclusion: The current information on cross-talk of EGFR and HDACs would likely assist researchers in designing and developing dual or multitargeted inhibitors through combining the required pharmacophores.

背景：EGFR在多种癌症中均过表达。因此，它成为最有利的药物靶标之一。长期使用的单作用EGFR抑制剂可诱导耐药性和副作用。双重/联合/多靶点疗法对EGFR和/或其相互作用蛋白的抑制作用可以产生更有效的药物，而产生的耐药性更少或没有。

目的：该综述深入探讨了EGFR介导的内吞作用，从而导致其与HDAC的运输，内在化和串扰。

方法和结果：提出本综述的目的是汇总有关EGFR的相关文献，其对癌症预后的影响，抑制剂及其通过乙酰化对其运输的调控，以及通过成功地通过双重干预成功靶向这些蛋白（EGFR和HDAC）的当前策略。 /混合/联合化疗。

结论：有关EGFR和HDAC相互干扰的最新信息可能会帮助研究人员通过组合所需的药效团来设计和开发双重或多目标抑制剂。