Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence

Abstract

Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment. The developments of the molecular mechanisms on cancer progression provide insight into novel targeted therapies, which are emerging as groundbreaking and promising cancer treatment strategies. In gynecologic malignancies, potential therapeutic targeted agents include antiangiogenic agents, poly (ADP-ribose) polymerase (PARP) inhibitors, tumor-intrinsic signaling pathway inhibitors, selective estrogen receptor downregulators, and immune checkpoint inhibitors. In this article, we provide a comprehensive review of the clinical evidence of targeted agents in gynecological cancers and discuss the future implication.

Fig. 1

The VEGF, PI3K/AKT/mTOR, and Ras/Raf/MEK signal transduction pathway and therapeutic interventions. After ligand binding, the receptors initiate the signaling cascade reaction, which is overactive in cancer cells. The figure shows the main elements in those pathways and the therapeutic agents

Fig. 2

Base-excision repair/single-strand break pathway and the mechanism of synthetic lethal interactions. Inhibition of PARP-1 causes the accumulation of DNA SSBs and ultimately results in DSBs during DNA replication. In cells with HRD, DSBs are left unrepaired or repaired by the error-prone NHEJ pathway, which result in genomic instability and ultimately cell death

Fig. 3

The HER signal transduction pathway and therapeutic interventions

Fig. 4

The HGF/c-MET signal transduction pathway and therapeutic interventions

Fig. 5

The immune checkpoint blockades. Antigen presenting cells (APC) take up antigen (Ag) released from tumor cells and present it to T cells. PD-1 receptors inhibit immune responses by engagement of PD-L1 and PD-L2. Therefore, monoclonal antibody blockading the PD-1 pathway results in enhancing antitumor immunity