Table 1.
Summary of indirect targeting therapies in recent years.
| Strategies for targeted therapy | Drugs, compounds or key genes used | The core of therapeutic strategy (Characteristics of mtDNA targeting) | Cancer | year | |
|---|---|---|---|---|---|
| Wang et al. (Wang et al., 2023) | Influence genetic functions of mtDNA, increasing ROS | TFAM and gemcitabine | Inhibition of TFAM results in mitochondrial dysfunction, amplifies gemcitabin-induced oxidative stress, and augments cytotoxicity. | Pancreatic cancer | 2023 |
| Yin et al. (Yin et al., 2023) | Activate immunity | Raddeanin A | It could bind to TDP-43, induce mtDNA leakage, and ultimately enhance DC-mediated antigen cross-presentation and T cell activation. | Melanoma and colon cancer | 2023 |
| Xiao et al. (Xiao et al., 2022) | Activate immunity | PLGA@Icaritin NPs | Resulted in overproduction of oxidative-mitochondrial DNA, which activates the release of DAMPs | Gastric cancer | 2022 |
| Li et al. (Li et al., 2022) | Activate immunity | (BPA + CPI)@PLGA NPs | The release of mtDNA caused by mitochondrial metabolism disorder further activated the cGAS/STING signal pathway | Liver cancer | 2022 |
| Witkowska et al. (Witkowska et al., 2022) | Activate immunity | Ethyl 3-((tert-butoxycarbonyl)amino)-2-hydroxy-9H-carbazole-1-carboxylate; 3-((tert-butoxycarbonyl) amino)-2-hydroxy-9H-carbazole-1-carboxylic acid | It induced the release of mtDNA into the cytosol by increasing the permeabilization of the mitochondrial IM, which could lead to cell death-associated inflammation | Colon cancer and osteosarcoma | 2022 |
| Zhao et al. (Zhao et al., 2022) | Activate immunity | A herpesvirus-mimicking nanoparticle (named Vir-ZM@TD) | Vir-ZM@TD evaded rapid clearance in the blood circulation and mimicked the serial infection processes of herpesvirus, including TFAM deficiency-triggered mtDNA stress, as well as the release of Mn2+ from organelles into the cytosol, priming cGAS-STING pathway-mediated innate immunity. | Breast carcinoma | 2022 |
| Yan et al. (Yan et al., 2022) | Activate immunity | RocA | RocA promoted NK cell infiltration by activating cGAS-STING signaling via targeting mtDNA. | NSCLC | 2022 |
| Benedetti et al. (Benedetti et al., 2022) | Increase ROS | Acyclovir | The continuous generation of ROS caused dose-dependent damage to mtDNA | NSCLC | 2022 |
| Somuncu et al. (Somuncu et al., 2022) | Increase ROS, influence genetic functions of mtDNA | 3,3'-[(1,1′-Biphenyl)-4′,4′-diyl)bis (azo)]bis [4-amino-1-naphthalenesulfonic acid](CR) | CR was a high-affinity binder to the Pol γ protein, causing mitochondrial dysfunction by inhibiting Pol γ activity and oxidative mtDNA damage repair. | Colonic carcinoma | 2022 |
| Wang et al. (Wang et al., 2022a) | Influence genetic functions of mtDNA | CircRNAs | miR-1182/TFAM axis was inhibited, resulting in transcriptional repression of ND1 and ATP6 | NSCLC | 2022 |
| Kong et al. (Kong et al., 2022) | Influence genetic functions of mtDNA | The combination of epoxomicin and cisplatin | Inhibition of TFAM and POLRMT function, affecting mitochondrial genome transcription | ovarian carcinoma | 2022 |
| Guo et al. (Guo et al., 2022) | Influence genetic functions of mtDNA, increase ROS | VB12- sericin-PBLG-IR780 | VB12- sericin-PBLG-IR780 could significantly inhibit the expression of ATP synthase and lead to ROS generation. | Gastric cancer | 2022 |
| Hu et al. (Hu et al., 2021) | Activate immunity | ATM protein inhibition | ATM inhibition potently activated the cGAS/STING pathway and enhanced lymphocyte infiltration into the TME by TFAM, leading to mtDNA leakage into the cytoplasm. | Breast carcinoma and melanoma | 2021 |
| Jiang et al. (Jiang, Guo, et al., 2021) | Activate immunity, metal complexes | MSN-Ru2+/Fe2+ | MSN-Ru2+/Fe2+ could enter mitochondria to bind with mtDNA due to the lipophilic and DNA affinity of Ru2+ complex. Oxidative mtDNA is able to escape from the tumor cells and results in the reactivated immunoresponse of macrophages against cancer cells. | Pancreatic cancer | 2021 |
| Panchangam et al. (Panchangam et al., 2021) | Increase ROS | Novel C–N-cyclometalated 2H-indazole-Ir(III) complex | Increased ROS damage mtDNA. And mtDNA may also be damaged as a target during metal delivery. | Triple negative mammary gland cancer | 2021 |
| Koshikawa et al. (Koshikawa et al., 2021) | Increase ROS, carrier system | A five-ring PIP-TPP | It localized in the mitochondria in HeLamtA3243G cells and induced mitochondrial ROS production, mitophagy and apoptosis in a mutation-specific fashion | Cervical carcinoma | 2021 |
| Li et al. (Li, Zhang, et al., 2021) | Influence genetic functions of mtDNA, Activate immunity | Zalcitabine | Zalcitabine-induced TFAM degradation could trigger oxidative DNA damage, mtDNA release to the cytosol, and subsequent activation of the CGAS-STING1 pathway | Pancreatic cancer | 2021 |
| Cheng et al. (Cheng et al., 2020) | Activate immunity | Overexpression of Lon | Upregulation of Lon induced the secretion of extracellular vehicles, which carry mtDNA and PD-L1. | Oral squamous cell carcinoma | 2020 |
| Pandey et al. (Pandey & Verma, 2020) | Influence genetic functions of mtDNA | Violacein and silver nanoparticles | Dyad drug system could structurally bind and inhibit TFAM at the interface of TFAM-DNA complex during replication and thus can hinder majority of pathways contributing to cancer proliferation. | Pan-carcinoma | 2020 |
| Bonekamp et al. (Bonekamp et al., 2020) | Influence genetic functions of mtDNA | IMTs | IMT1 and IMT1B significantly reduced the levels of mtDNA transcriptions and respiratory chain subunits in tumor cells by inhibiting POLRMT. | NSCLC, cervical carcinoma and ovarian carcinoma | 2020 |
| Inamura et al. (Inamura et al., 2019) | Increase ROS | Gemcitabine | Gemcitabine depleted the cellular pool of deoxyribonucleotides and inhibits the synthesis of mtDNA，resulting in the acceleration of ROS generation in mitochondria. | Insulinoma | 2019 |
| Fan et al. (Fan et al., 2017) | Influence genetic functions of mtDNA | miR-199a-3p | The up-regulation of miR-199a-3p expression could inhibit mitochondria by inhibiting TFAM transcription | Breast carcinoma | 2017 |