| Numbers of new cases in 2020 indicated that breast cancer surpassed lung cancer for the first time as the most commonly diagnosed cancer worldwide;meanwhile,breast cancer has been one of the leading causes of female cancer death.Although great progress has been continuously made in treatment of breast cancer in recent years,there are still quite a few unresolved problems in clinical practice,such as whether one-year adjuvant trastuzumab therapy is a "standard" course for treating HER2-positive early breast cancer.Moreover,there are presently various disadvantages to the approaches for treating breast cancer,and recurrence and metastasis of cancer cells remain a challenging problem to be solved.Therefore,it is practically necessary to develop novel therapies.Trastuzumab may significantly reduce the risk of HER2-positive breast cancer recurrence and improve patients’prognosis.However,the optimum duration of adjuvant trastuzumab therapy remains a controversial issue.Thus,based on currently available clinical data and the latest research findings,we conducted a comparative investigation into the efficacy and cardiotoxicity of short-course and one-year adjuvant trastuzumab therapies by means of meta-analysis.The results indicated that one-year adjuvant trastuzumab therapy significantly increased patients’ disease-free survival(DFS)(HR=1.13;95%CI=1.03-1.25;p=0.01;I2=0%)and overall survival(OS)(HR=1.16;95%CI=1.01-1.32;p=0.03;I2=0%),attesting to the fact that one-year trastuzumab targeted therapy is still the standard therapeutic regimen for patients with HER2-positive early breast cancer.Nonetheless,the one-year therapy also increased the incidence of cardiotoxicity(OR=0.52;95%Cl=0.43-0.62;p<0.00001),suggesting that a short-course therapy could be a potential option for patients with underlying heart conditions or a low risk of breast cancer recurrence.At present,there are multiple sophisticated therapeutic regimens for breast cancer,such as biological-targeted treatment including trastuzumab and surgical treatment,but they also have different weaknesses.Therefore,it is necessary to develop new methods of treatment.As a non-invasive method,photodynamic therapy has attracted great attention because of its merits like low levels of toxic response and drug resistance.In our study,a novel near-infrared photosensitizer(TTRE)with D-π-A structure was designed for photodynamic therapy.Through a series of experiments,including characterization of optical properties,detection of reactive oxygen species,and two-photon fluorescence imaging,it was proved that TTRE has the characteristics of near-infrared emission,large Stokes shift(175 nm),high photostability and strong penetrability,and could be used as an efficient photosensitizer for photodynamic therapy guided by two-photon fluorescence and near-infrared fluorescence imaging.TTRE’s outstanding performance in photodynamic therapy has also been further demonstrated in both in vitro and in vivo experiments,thus providing more options for the development of novel fluorescence imaging-guided photodynamic therapy.Conventional photodynamic therapy lacks targeting,and the reactive oxygen species produced by photodynamic therapy could reverse resistance to trastuzumab,which has the ability to target cancer cells.Hence we integrated a structural analogue of a novel photosensitizer(TTRE)with trastuzumab,to synthesize a new targeted near-infrared fluorescent nanoprobe,Tra-TTR-A,in the hope of combining these two therapies in a complementary manner.Experiments have shown that Tra-TTR-A is characterized by near-infrared emission and large Stokes shift(210 nm),having advantages in terms of fluorescence imaging.In addition,Tra-TTR-A has the ability to produce ROS efficiently,target and bind to HER2 receptors,and achieve precise destruction of HER2-positive breast cancer.Therefore,Tra-TTR-A could be expected to play a role in the development of targeted fluorescence imaging and targeted photodynamic therapy for breast cancer,so as to accomplish integration of diagnosis and treatment of breast cancer. |
PDF Full Text Request