Overexpressed SIRT6 ameliorates doxorubicin-induced cardiotoxicity and potentiates the therapeutic efficacy through metabolic remodeling

Since the utilization of anthracyclines in cancer therapy, severe cardiotoxicity has become a major obstacle. The major challenge in treating cancer patients with anthracyclines is minimizing cardiotoxicity without compromising antitumor efficacy. Herein, histone deacetylase SIRT6 expression was reduced in plasma of patients treated with anthracyclines-based chemotherapy regimens. Furthermore, overexpression of SIRT6 alleviated doxorubicin-induced cytotoxicity in cardiomyocytes, and potentiated cytotoxicity of doxorubicin in multiple cancer cell lines. Moreover, SIRT6 overexpression ameliorated doxorubicin-induced cardiotoxicity and potentiated antitumor efficacy of doxorubicin in mice, suggesting that SIRT6 overexpression could be an adjunctive therapeutic strategy during doxorubicin treatment. Mechanistically, doxorubicin-impaired mitochondria led to decreased mitochondrial respiration and ATP production. And SIRT6 enhanced mitochondrial biogenesis and mitophagy by deacetylating and inhibiting Sgk1. Thus, SIRT6 overexpression coordinated metabolic remodeling from glycolysis to mitochondrial respiration during doxorubicin treatment, which was more conducive to cardiomyocyte metabolism, thus protecting cardiomyocytes but not cancer cells against doxorubicin-induced energy deficiency. In addition, ellagic acid, a natural compound that activates SIRT6, alleviated doxorubicin-induced cardiotoxicity and enhanced doxorubicin-mediated tumor regression in tumor-bearing mice. These findings provide a preclinical rationale for preventing cardiotoxicity by activating SIRT6 in cancer patients undergoing chemotherapy, but also advancing the understanding of the crucial role of SIRT6 in mitochondrial homeostasis.

Antibody-drug conjugates in HER2-positive breast cancer / 中华医学杂志(英文版)

Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease / 中华肿瘤杂志

The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.

Comparison of predictive value of different risk assessment models for venous thromboembolism in elderly patients with lung cancer / 中华老年医学杂志

Objective:To explore the predictive value of the COMPASS-cancer associated thrombosis(COMPASS-CAT)risk assessment model and the modified Khorana risk assessment model for the risk of venous thromboembolism(VTE)in elderly patients with lung cancer.Methods:A retrospective analysis was conducted on clinical data of 276 hospitalized lung cancer patients aged 60 years and over in the Cancer Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College from March 2013 to March 2017.Patients were divided into the VTE group(n=39)and the non-VTE group(n=237). The COMPASS-CAT model and the modified Khorana model were used to evaluate the risk of venous thromboembolism in the two groups.The sensitivity, specificity and Youden index of the two models were calculated.The receiver-operating characteristics(ROC)curves of the two evaluation models were drawn.The predictive effect and influence of two evaluation models on VTE risk in elderly lung cancer patients were compared by using Medcalc software analysis and multivariate Logistic regression analysis.Results:The incidence of VTE was 14.13%(39/276). The sensitivity, specificity, Youden index and the AUC under ROC curves of the COMPASS-CAT model and the modified Khorana model were 0.718 and 0.795, 0.861 and 0.527, 0.524 and 0.348, and 0.789 and 0.661, respectively.Using the Medcalc software to compare the two models, the area under the curve of the COMPASS-CAT risk assessment model was increased by 0.128, compared with the modified Khorana model( Z=2.676, P=0.0075). Multivariate Logistic regression analysis showed that COMPASS-CAT≥7 points and Khorana≥2 points were independent risk factors for VTE in elderly patients with lung cancer( P<0.05). Conclusions:The modified Khorana model can predict the risk of VTE in elderly patients with lung cancer, but the accuracy of prediction is low.The COMPASS-CAT model has a higher predictive value for VTE risk assessment than the modified Khorana model and is more suitable for elderly patients with lung cancer.

Application of circulating tumor DNA in endocrine therapy resistance of breast cancer / 国际肿瘤学杂志

Although most hormone-receptor positive breast cancer patients initially respond to endocrine treatment,they will eventually acquire resistance to endocrine therapy.Therefore,during clinical treatment,it is of great importance to continuously monitor for resistant mutations.Circulating tumor DNA (ctDNA) has become more prevalent because it is non-invasive,convenient,rapid,and can quickly assess the overall situation of the tumor.With the maturity of next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR),the establishment of endocrine treatment resistance mutation monitoring system has become possible.