Review of robotic systems for thoracoabdominal puncture interventional surgery.

Cancer, with high morbidity and high mortality, is one of the major burdens threatening human health globally. Intervention procedures via percutaneous puncture have been widely used by physicians due to its minimally invasive surgical approach. However, traditional manual puncture intervention depends on personal experience and faces challenges in terms of precisely puncture, learning-curve, safety and efficacy. The development of puncture interventional surgery robotic (PISR) systems could alleviate the aforementioned problems to a certain extent. This paper attempts to review the current status and prospective of PISR systems for thoracic and abdominal application. In this review, the key technologies related to the robotics, including spatial registration, positioning navigation, puncture guidance feedback, respiratory motion compensation, and motion control, are discussed in detail.

Theoretical error analysis of spotlight-based instrument localization for retinal surgery.

Retinal surgery is widely considered to be a complicated and challenging task even for specialists. Image-guided robot-assisted intervention is among the novel and promising solutions that may enhance human capabilities therein. In this paper, we demonstrate the possibility of using spotlights for 5D guidance of a microsurgical instrument. The theoretical basis of the localization for the instrument based on the projection of a single spotlight is analyzed to deduce the position and orientation of the spotlight source. The usage of multiple spotlights is also proposed to check the possibility of further improvements for the performance boundaries. The proposed method is verified within a high-fidelity simulation environment using the 3D creation suite Blender. Experimental results show that the average positioning error is 0.029 mm using a single spotlight and 0.025 mm with three spotlights, respectively, while the rotational errors are 0.124 and 0.101, which shows the application to be promising in instrument localization for retinal surgery.

One Step Encapsulation of Mesenchymal Stromal Cells in PEG Norbornene Microgels for Therapeutic Actions.

Cell therapies require control over the cellular response under standardized conditions to ensure continuous delivery of therapeutic agents. Cell encapsulation in biomaterials can be particularly effective at providing cells with a uniformly supportive and permissive cell microenvironment. In this study, two microfluidic droplet device designs were used to successfully encapsulate equine mesenchymal stromal cells (MSCs) into photopolymerized polyethylene glycol norbornene (PEGNB) microscale (∼100-200 µm) hydrogel particles (microgels) in a single on-chip step. To overcome the slow cross-linking kinetics of thiol-ene reactions, long dithiol linkers were used in combination with a polymerization chamber customized to achieve precise retention time for microgels while maintaining cytocompatibility. Thus, homogeneous cell-laden microgels could be continuously fabricated in a high-throughput fashion. Varying linker length mediated both the gel formation rate and material physical properties (stiffness, mass transport, and mesh size) of fabricated microgels. Postencapsulation cell viability and therapeutic indicators of MSCs were evaluated over 14 days, during which the viability remained at least 90%. Gene expression of selected cytokines was not adversely affected by microencapsulation compared to monolayer MSCs. Notably, PEGNB-3.5k microgels rendered significant elevation in FGF-2 and TGF-ß on the transcription level, and conditioned media collected from these cultures showed robust promotion in the migration and proliferation of fibroblasts. Collectively, standardized MSC on-chip encapsulation will lead to informed and precise translation to clinical studies, ultimately advancing a variety of tissue engineering and regenerative medicine practices.

Robotic ultrasound imaging: State-of-the-art and future perspectives.

Ultrasound (US) is one of the most widely used modalities for clinical intervention and diagnosis due to the merits of providing non-invasive, radiation-free, and real-time images. However, free-hand US examinations are highly operator-dependent. Robotic US System (RUSS) aims at overcoming this shortcoming by offering reproducibility, while also aiming at improving dexterity, and intelligent anatomy and disease-aware imaging. In addition to enhancing diagnostic outcomes, RUSS also holds the potential to provide medical interventions for populations suffering from the shortage of experienced sonographers. In this paper, we categorize RUSS as teleoperated or autonomous. Regarding teleoperated RUSS, we summarize their technical developments, and clinical evaluations, respectively. This survey then focuses on the review of recent work on autonomous robotic US imaging. We demonstrate that machine learning and artificial intelligence present the key techniques, which enable intelligent patient and process-specific, motion and deformation-aware robotic image acquisition. We also show that the research on artificial intelligence for autonomous RUSS has directed the research community toward understanding and modeling expert sonographers' semantic reasoning and action. Here, we call this process, the recovery of the "language of sonography". This side result of research on autonomous robotic US acquisitions could be considered as valuable and essential as the progress made in the robotic US examination itself. This article will provide both engineers and clinicians with a comprehensive understanding of RUSS by surveying underlying techniques. Additionally, we present the challenges that the scientific community needs to face in the coming years in order to achieve its ultimate goal of developing intelligent robotic sonographer colleagues. These colleagues are expected to be capable of collaborating with human sonographers in dynamic environments to enhance both diagnostic and intraoperative imaging.

The role of ferroptosis mediated by Bmal1/Nrf2 in nicotine -induce injury of BTB integrity.

Nicotine has shown the toxic effects on male reproductive system, and testicular damage is associated with ferroptosis, which is a non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. However, the role of nicotine on ferroptosis of testicular cells is largely elusive. In the present study, we showed that nicotine destroyed blood-testis barrier (BTB) by interfering with the circadian rhythm of BTB-related factors (ZO-1, N-Cad, Occludin and CX-43) and induced ferroptosis, as reflected via increased clock-control levels of lipid peroxide and decreased ferritin and GPX4, which involved in the circadian. Inhibition of ferroptosis with Fer-1 alleviated nicotine-induced injury of BTB and impaired sperm in vivo. Mechanically, we uncover that the core molecular clock protein, Bmal1, regulates the expression of Nrf2 via direct E-box binding to its promoter to regulate its activity, and nicotine decreases the transcription of Nrf2 through Bmal1 and inactivates Nrf2 pathway and its downstream antioxidant gene, which leads to the imbalance of redox state and ROS accumulation. Intriguingly, nicotine induced lipid peroxidation and subsequent ferroptosis by Bmal1-mediated Nrf2. In conclusion, our study reveals a clear role for the molecular clock in controlling Nrf2 in testis to mediate the ferroptosis induced by nicotine. These findings provide a potential mechanism to prevent smoking and/or cigarette smoke-induced male reproductive injury.

PHB2 binds to ERß to induce the autophagy of porcine ovarian granulosa cells through mTOR phosphorylation.

Autophagy of ovarian granulosa cells is one of the reasons which results in follicular atresia. PHB2 regulates many fundamental biological processes and is pivotal in the mitophagy of cells; nevertheless, the autophagy in the porcine ovary and how PHB2 regulates the follicular cells are unknown. Here we report a protein complex that induces autophagy in porcine granulosa cells (PGCs) through the direct interaction of ERß and PHB2. In this study, we aimed to elucidate the autophagy and the role of PHB2 in porcine ovaries using porcine primary ovarian granulosa cells (PGCs). The results showed that PHB2 induces PGCs autophagy because of the change in related genes and protein expression levels. In addition, the results of Co-IP and the distribution of the combination of PHB2 and ERß showed that this complex is also indicated as an essential role of PHB2 in PGCs autophagy. Based on our results, it can be concluded that PHB2 combined with ERß induces PGCs autophagy by targeting the mTOR pathway. This study pinpoints a novel regulatory mechanism of autophagy and demonstrates the existence of a protein complex that may underlie its roles in autophagy in PGCs.

HDAC/JAK dual target inhibitors of cancer-related targets: The success of nonclearable linked pharmacophore mode.

In recent years, the development of dual target drugs has become a research hotspot in cancer treatment and the reasonable design of the drugs is critical. The nonclearable linked pharmacophore mode is one of the commonly used strategies for designing dual target drugs, it can connect the pharmacophores of two synergistic target inhibitors into one molecule through the linker, which greatly improves the utilization of drugs. Epigenetic modifications as a potential treatment for multiple diseases have always been a subject of great concern, and Histone deacetylases (HDAC) plays an important role. Janus Kinase (JAK) is a family of intracellular non-receptor tyrosine kinases that transduce cytokine-mediated signals through the JAK-signal transducers and the activators of transcription (STAT) pathway. Studies showed the combination of HDAC and JAK inhibitors exhibited synergistic effects in breast cancer treatment [1]. In addition, the pharmacophore models of the aforementioned two inhibitors indicate similar essential features. Further investigation on recent years' progress in the field demonstrated the nonclearable linked pharmacophore mode, using different length carbon chains as linkers to connect the pharmacophores of the two inhibitors, is the main strategy to design HDAC/JAK dual-target inhibitors which has been verified to be effective in biological activity tests. This review takes recent years' HDAC/JAK dual target inhibitors' development details as an example to summarize the general ideas behind the scene. We wish to provide the readers a theoretical basis for the development of more efficient dual-target or multi-target drugs in future.

Expression of ERß induces bovine ovarian granulosa cell autophagy via the AKT/mTOR pathway.

The aim of our study was to determine whether silencing or overexpression of estrogen receptor ß (ERß) regulates cell proliferation, steroidogenesis, autophagy and signalling pathways in bovine ovarian granulosa cells in vitro. In this study, bovine ovarian granulosa cells (BGCs) were cultured and transfected with ERß siRNA (si-ERß) or a plasmid overexpressing ERß (oe-ERß), and CCK-8 kit was used to assess cell proliferation. Real-time PCR was used to measure gene transcription. Western blotting was used to measure protein expression, and a specific kit was used to measure the production of steroid hormones. The results showed the expression level of ERß affects BGC proliferation according to the gene transcription levels of FSHR, CYP19A1, HSD3ß1 and STAR and the production of E2 and P4. ERß was identified as an important nuclear receptor that induced BGC autophagy based on the mRNA and protein expression of autophagy-related genes. Furthermore, the role of ERß in BGC autophagy was confirmed through treatment with rapamycin (RAPA) or 3-methyladenine (3-MA) in BGCs by cotransfection with si-ERß or oe-ERß in BGCs. The results related to AKT/mTOR signalling and phosphorylation suggested that ERß induces BGC autophagy through attenuating AKT/mTOR signalling. In summary, this study demonstrates that silencing or overexpression of ERß regulates BGC proliferation and function and induces BGC autophagy by targeting AKT/mTOR signalling. These data reveal a novel regulatory mechanism of autophagy via ERß and provide insights into the role of autophagy in BGCs.

Activin A attenuates apoptosis of granulosa cells in atretic follicles through ERß-induced autophagy.

It is well known that approximately 99% of ovarian follicles in mammals suffer from a degenerative process known as atresia, which is a huge waste of genetic resource in female animals. Studies have shown that activin A (ACT-A) is located in ovarian granulosa cells and has different effects in granulosa cell depending on species. Although granulosa cells play a critical role during follicular atresia, the mechanism of action of ACT-A in bovine ovarian granulosa cells (BGC) is poorly understood. In this study, we first determined the apoptosis of BGCs isolated from growth follicles and atretic follicles respectively. Then, BGC isolated from atretic follicles were used as a model to elucidate the role of ACT-A in cattle ovary. The results showed that apoptosis occurred in both growing follicles and atretic follicles, and the percentage of apoptotic cells in atretic follicles was higher than that in growing follicles. The current results indicated that ACT-A can attenuate apoptosis of BGC by maintaining the function of BGC in atretic follicles. Increased ERß induced by ACT-A promoted BGC autophagy but had no effect on apoptosis. In summary, this study suggests that ACT-A attenuates BGC apoptosis in atretic follicles by ERß-mediated autophagy signalling.

Diffeomorphic respiratory motion estimation of thoracoabdominal organs for image-guided interventions.

PURPOSE: Percutaneous image-guided interventions are commonly used for the diagnosis and treatment of cancer. In practice, physiological breathing-induced motion increases the difficulty of accurately inserting needles into tumors without impairing the surrounding vital structures. In this work, we propose a data-driven patient-specific hierarchical respiratory motion estimation framework to accurately estimate the position of a tumor and surrounding vital tissues in real time. METHODS: The motion of optical markers attached to the chest or abdomen skin is used as a surrogate signal to estimate tumor motion based on ɛ-support vector regression (ɛ-SVR). With the estimated tumor motion as the input, a novel respiratory motion model is developed to estimate the diffeomorphic deformation field of the whole organ (liver or lung) without intraoperative, iterative optimization computations. The respiratory motion model of the whole organ is established in Lie algebra space based on the kriging algorithm to ensure that the estimated deformation field is diffeomorphic, optimal, and unbiased. Preoperative prior knowledge for modeling the motion of whole organs is obtained by deformation registration between four-dimensional computed tomography (4D CT) images using a hybrid diffeomorphic registration method. RESULTS AND CONCLUSIONS: Experimental results on an in vivo beagle dog show that the minimum value of the determinant of the Jacobian of the estimated deformation field is greater than zero, so the estimated deformation field of the whole liver with our method is diffeomorphic. The mean position error of the tumor is 1.2 mm corresponding to a mean accuracy improvement of 76.5%, and the mean position error of the whole liver is 2.1 mm, corresponding to a mean accuracy improvement of 37.9%. The experimental results based on public human subject data show that the mean position error of the tumor is 1.1 mm, corresponding to a mean accuracy improvement of 83.1%, and the mean position error of the whole lung is 2.1 mm, corresponding to a mean accuracy improvement of 41.4%. The positioning errors for the tumor and whole organ are hierarchical and consistent with clinical demand.

High doses of FSH induce autophagy in bovine ovarian granulosa cells via the AKT/mTOR pathway.

Follicle-stimulating hormone (FSH) plays a critical role in follicular growth and granulosa cell function; however, the mechanism by which the aggressive stimulation of FSH leads to poorer oocyte quality and embryo development potential is unclear. In this study, bovine ovarian granulosa cells (BGCs) were challenged with FSH doses (vehicle, 0.1, 1, 10 and 100 ng/ml) to investigate the effects of FSH on BGCs. The results indicated that the relative viability of BGCs was significantly increased in cells challenged with 1 ng/ml FSH, whereas the viability was significantly decreased with 100 ng/ml FSH treatment. The mRNA abundance of FSHR, CYP19, StAR and BAX was significantly upregulated with 1, 10 and 100 ng/ml of FSH, while the BCL-2 mRNA level was downregulated with higher concentrations of FSH (10 and 100 ng/ml). Furthermore, BGC autophagy was detected in cells treated with 10 and 100 ng/ml FSH by MDC staining, and the mRNA abundance of LC3, BECN1, BNIP3, ATG3 and ATG7 was upregulated with increasing FSH concentration. Meanwhile, the protein expression of LC3 was increased in cells treated with 10 and 100 ng/ml FSH. 1 and 10 ng/ml FSH significantly increased E2 production, whereas 10 and 100 ng/ml FSH significantly increased P4 production. FSH significantly inhibited the phosphorylation of AKT in cells treated with higher concentrations (1, 10 and 100 ng/ml), while activating mTOR phosphorylation at concentrations of 10 and 100 ng/ml of FSH. In summary, we can conclude that higher doses of FSH (10 and 100 ng/ml) induce BGC autophagy via the AKT/mTOR signalling pathway.

WITHDRAWN:Estrogen receptor ß (ERß) induces bovine ovarian granulosa cell (BGC) autophagy via the AKT/mTOR pathway.

Ahead of Print article withdrawn by Editorial Board.

Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials.

Protein-protein interactions (PPIs) have pivotal roles in life processes. The studies showed that aberrant PPIs are associated with various diseases, including cancer, infectious diseases, and neurodegenerative diseases. Therefore, targeting PPIs is a direction in treating diseases and an essential strategy for the development of new drugs. In the past few decades, the modulation of PPIs has been recognized as one of the most challenging drug discovery tasks. In recent years, some PPIs modulators have entered clinical studies, some of which been approved for marketing, indicating that the modulators targeting PPIs have broad prospects. Here, we summarize the recent advances in PPIs modulators, including small molecules, peptides, and antibodies, hoping to provide some guidance to the design of novel drugs targeting PPIs in the future.

miRNA-21-3p targeting of FGF2 suppresses autophagy of bovine ovarian granulosa cells through AKT/mTOR pathway.

It is widely thought that the main reason for ovarian follicular atresia is apoptosis of granulosa cells, however, accumulating evidence suggests that autophagy plays a role in the fate of granulosa cells. Although epigenetic regulation including miR-21-3p associated with autophagy process has been reported in many cancer types, nevertheless, the mechanism of miR-21-3p in bovine ovary is poorly understood. In the present study, bovine ovarian granulosa cells (BGCs) were used as a model to elucidate the autophagy and role of miR-21-3p in a cattle ovary. The results from gene expression and tagged autophagosomes showed the autophagy in BGCs and miR-21-3p was identified as an important miRNA regulating autophagy of BGCs. The current results indicated that FGF2 was a validated target of miR-21-3p in autophagy regulation of BGCs according to the results from FGF2 luciferase reporter assays and FGF2 overexpression (oe-FGF2) or small interference (si-FGF2). Transfection of miR-21-3p mimic and si-FGF2 plasmids resulted in decreasing phosphorylated AKT and mTOR, while transfection of miR-21-3p inhibitor and oe-FGF2 increased the phosphorylated level of AKT and mTOR in BGCs. These data indicate that regulation of miR-21-3p on BGCs autophagy through AKT/mTOR pathway. In summary, this study suggests that miR-21-3p targets FGF2 to inhibit BGCs autophagy by repressing AKT/mTOR signaling.

Recent research progress on natural small molecule bibenzyls and its derivatives in Dendrobium species.

Orchidaceous plant Dendrobium genus is often used as a tonic, and its phenolic components have attracted attention for its anti-tumor and anti-diabetic complications. Bibenzyls is one of the essential phenolic active ingredients in the Dendrobium genus. At present, 89 bibenzyl derivatives have been extracted and identified from 46 Dendrobium species. The activity studies have shown that 42 compounds have pharmaceutical activity. Among them, 23 compounds showed antitumor activity; 7 compounds showed anti-diabetes and its complications activity; 10 compounds exhibited neuroprotective effects; 18 compounds showed antioxidant effects; 11 compounds had anti-inflammatory activity; 3 compounds had Antiplatelet aggregation effects; 3 compounds had antibacterial and antiviral effects. The Bibenzyls is small-molecular compounds of natural origin and widely sourced. Previous studies showed that the bibenzyls has good anti-tumor, anti-diabetes and its complications, and neuroprotective effects, and it has great potential for treating tumors, diabetes and its complications, Alzheimer's disease (AD) and Parkinson's disease (PD). Additionally, compounds such as moscatilin (1), gigantol (2) and chrysotoxine (3) have been further studied as lead compounds, and compounds exhibited therapeutical effects had been synthesized. Enough pieces of evidences have shown that the Bibenzyls have good development prospects. This article reviews the pharmacological effects of bibenzyls in Dendrobium species and provides an idea for its further development.

Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase ß and a de novo DNA Methyltransferase.

DNA damage and base excision repair (BER) are actively involved in the modulation of DNA methylation and demethylation. However, the underlying molecular mechanisms remain unclear. In this study, we seek to understand the mechanisms by exploring the effects of oxidative DNA damage on the DNA methylation pattern of the tumor suppressor breast cancer 1 (BRCA1) gene in the human embryonic kidney (HEK) HEK293H cells. We found that oxidative DNA damage simultaneously induced DNA demethylation and generation of new methylation sites at the CpGs located at the promoter and transcribed regions of the gene ranging from -189 to +27 in human cells. We demonstrated that DNA damage-induced demethylation was mediated by nucleotide misincorporation by DNA polymerase ß (pol ß). Surprisingly, we found that the generation of new DNA methylation sites was mediated by coordination between pol ß and the de novo DNA methyltransferase, DNA methyltransferase 3b (DNMT3b), through the interaction between the two enzymes in the promoter and encoding regions of the BRCA1 gene. Our study provides the first evidence that oxidative DNA damage can cause dynamic changes in DNA methylation in the BRCA1 gene through the crosstalk between BER and de novo DNA methylation.

State recognition of decompressive laminectomy with multiple information in robot-assisted surgery.

The decompressive laminectomy is a common operation for treatment of lumbar spinal stenosis. The tools for grinding and drilling are used for fenestration and internal fixation, respectively. The state recognition is one of the main technologies in robot-assisted surgery, especially in tele-surgery, because surgeons have limited perception during remote-controlled robot-assisted surgery. The novelty of this paper is that a state recognition system is proposed for the robot-assisted tele-surgery. By combining the learning methods and traditional methods, the robot from the slave-end can think about the current operation state like a surgeon, and provide more information and decision suggestions to the master-end surgeon, which aids surgeons work safer in tele-surgery. For the fenestration, we propose an image-based state recognition method that consists a U-Net derived network, grayscale redistribution and dynamic receptive field assisting in controlling the grinding process to prevent the grinding-bit from crossing the inner edge of the lamina to damage the spinal nerves. For the internal fixation, we propose an audio and force-based state recognition method that consists signal features extraction methods, LSTM-based prediction and information fusion assisting in monitoring the drilling process to prevent the drilling-bit from crossing the outer edge of the vertebral pedicle to damage the spinal nerves. Several experiments are conducted to show the reliability of the proposed system in robot-assisted surgery.

Inhibition of base excision repair by natamycin suppresses prostate cancer cell proliferation.

Prostate cancer (PCa) progression is characterized by increased expression and transcriptional activity of the androgen receptor (AR). In the advanced stages of prostate cancer, AR significantly upregulates the expression of genes involved in DNA repair. Upregulation of expression for base excision repair (BER) related genes is associated with poor patient survival. Thus, inhibition of the BER pathway may prove to be an effective therapy for prostate cancer. Using a high throughput BER capacity screening assay, we sought to identify BER inhibitors that can synergize with castration therapy. An FDA-approved drug library was screened to identify inhibitors of BER using a fluorescence-based assay suitable for HTS. A gel-based secondary assay confirmed the reduction of BER capacity by compounds identified in the primary screen. Five compounds were then selected for further testing in the independently derived, androgen-dependent prostate cancer cell lines, LNCaP and LAPC4, and in the nonmalignant prostate derived cell lines PNT1A and RWPE1. Further analysis led to the identification of a lead compound, natamycin, as an effective inhibitor of key BER enzymes DNA polymerase ß (pol ß) and DNA Ligase I (LIG I). Natamycin significantly inhibited proliferation of PCa cells in an androgen depleted environment at 1 µM concentration, however, growth inhibition did not occur with nonmalignant prostate cell lines, suggesting that BER inhibition may improve efficacy of the castration therapies.

miR-21-3p inhibits autophagy of bovine granulosa cells by targeting VEGFA via PI3K/AKT signaling.

It is well documented that granulosa cell apoptosis is the main reason for follicular atresia and death; however, increasing evidence suggests that autophagy plays an important role in the fate of granulosa cells. miR-21-3p regulates many fundamental biological processes and is pivotal in the autophagy of tumor cells; nevertheless, the autophagy in cattle ovary and how miR-21-3p regulates the follicular cells is unknown. In this study, we aimed to elucidate the autophagy and the role of miR-21-3p in cattle ovary using bovine primary ovarian granulosa cells (BGCs). The results showed the autophagy for the first time in BGCs in large follicle according to autophagic gene transcript of LC3, BECN-1, ATG3, protein expression of LC3, P62 and LC3 puncta, a standard marker for autophagosomes. miR-21-3p was identified as a novel miRNA that repressed BGCs autophagy according to the results from plasmids transfection of miR-21-3p mimics and inhibitor. Meanwhile, VEGFA was confirmed to be a validated target of miR-21-3p in BGCs using luciferase reporter assays and the results of VEGFA expression decreased with transfection of miR-21-3p mimics, while it increased with transfection of miR-21-3p inhibitor. In addition, small interference-mediated knockdown of VEGFA significantly inhibits BGCs autophagy signaling; however, overexpression of VEGFA in BGCs promoted autophagy in the presence of miR-21-3p. Finally, the results of AKT and its phosphorylation suggested that miR-21-3p suppressed VEGFA expression through downregulating AKT phosphorylation signaling. In summary, this study demonstrates that miR-21-3p inhibits BGCs autophagy by targeting VEGFA and attenuating PI3K/AKT signaling.

Novel HER2-Targeting Antibody-Drug Conjugates of Trastuzumab Beyond T-DM1 in Breast Cancer: Trastuzumab Deruxtecan(DS-8201a) and (Vic-)Trastuzumab Duocarmazine (SYD985).

Targeted drug delivery has improved cancer treatment significantly in recent years, although it is difficult to achieve. Different approaches have been developed to apply targeted drug delivery. Among which, antibody-drug conjugate (ADC) provides a potentially ideal solution to such a challenge. ADC is an innovative drug treatment model with three key components: payload, monoclonal antibody, and linker. The monoclonal antibody targets the antigen-expressing tumor cells and internalizes the payload linked by the linker to the target cells to reduce the side effects of the traditional chemotherapy drugs. The off-target effect has an excellent therapeutic prospect. Among them, ado-trastuzumab emtansine (T-DM1) is a successful example of targeting human epidermal growth factor receptor-2 (HER2). Its antibody (trastuzumab) is derived from Herceptin with annual sales of more than $6 billion. It has excellent targeting and specific anti-tumor activity against HER2. Its linker is not cleavable and releases the Lys-linker-payload to kill the cells. The two ADCs described here use the same antibody as T-DM1, but the cleavable linker and the more toxic payload allow them to have the not only targeting of T-DM1, but also the reduce T-DM1 resistance and improve efficacy in heterogeneous tumors. This paper describes the mechanism of action and the biochemical characteristics of different parts and preclinical and clinical progress of trastuzumab deruxtecan(DS-8201a) and (vic-)trastuzumab duocarmazine (SYD985).