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Abstract Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

The real‐world benefits of adding androgen‐deprivation therapy (ADT) and its optimal duration when combined with current standard high‐dose radiation therapy (RT) remain unknown. We aimed to assess the efficacy of and toxicities associated with ADT in the setting of combination with high‐dose RT for intermediate‐risk (IR) and high‐risk (HR) prostate cancer (PCa). This article is a modified and detailed version of the commentary on Clinical Question 8 described in the Japanese Clinical Practice Guidelines for Prostate Cancer (ver. 2023). A qualitative systematic review was performed according to the Minds Guide. All relevant published studies between September 2010 and August 2020, which assessed the outcomes of IR or HR PCa treated with high‐dose RT, were screened using two databases (PubMed and ICHUSHI). A total of 41 studies were included in this systematic review, mostly consisting of retrospective studies (N = 34). The evidence basically supports the benefit of adding ADT to high‐dose RT to improve tumor control. Regarding IR populations, many studies suggested the existence of a subgroup for which adding ADT had no impact on either overall survival or the BF‐free duration. On the other hand, regarding HR populations, several studies suggested the positive impact of adding ADT for ≥1 year on overall survival. Adding ADT increases not only the risk of sexual dysfunction but also that of cardiovascular toxicities or bone fracture. Although the benefit of adding ADT was basically suggested for both IR and HR populations, further investigations are warranted to identify subgroups of patients for whom ADT has no benefit, as well as the appropriate duration of ADT for those who do derive benefit. [ABSTRACT FROM AUTHOR]

Simple Summary: Chordoma is a rare cancer that often occurs at the base of the skull. Treating skull base chordoma is challenging because the tumor is difficult to completely remove with surgery and has low radiosensitivity. This study compared two types of radiation modality: particle beam therapy (PT) and photon radiotherapy (RT). We found that PT provides better progression-free survival compared to photon RT. However, PT also has a higher risk of causing brain necrosis. Our findings suggest that PT is more effective for controlling skull base chordoma, but careful planning is needed to minimize side effects. [Objective] The aim of this study was to compare the efficacy of particle beam therapy (PT) with photon radiotherapy (RT) for treatment of skull base chordoma. [Methods] A systematic review was conducted for skull base chordoma treated with PT or photon RT reported from 1990 to 2022. Data were extracted for overall survival (OS) and progression-free survival (PFS), late adverse events, age, gender, gross total resection (GTR) rates, tumor volume, total irradiation dose, and treatment modality. Random-effects meta-regression analysis with the treatment modality as an explanatory variable was performed for each outcome to compare the modalities. [Results] A meta-analysis of 30 selected articles found 3- and 5-year OS rates for PT vs. photon RT or combined photon RT/proton beam therapy (PBT) of 90.8% (95% CI: 87.4–93.3%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6543; 80.0% (95% CI: 75.7–83.6%) vs. 89.5% (95% CI: 83.0–93.6%), p = 0.6787. The 5-year PFS rates for PT vs. photon RT or photon RT/PBT were 67.8% (95% CI: 56.5–76.7%) vs. 40.2% (95% CI: 31.6–48.7%), p = 0.0004. A random-effects model revealed that the treatment modality (PT vs. photon RT or photon RT/PBT) was not a significant factor for 3-year OS (p = 0.42) and 5-year OS (p = 0.11), but was a significant factor for 5-year PFS (p < 0.0001). The rates of brain necrosis were 8–50% after PT and 0–4% after photon RT or photon RT/PBT. [Conclusion] This study shows that PT results in higher PFS compared to photon RT for skull base chordoma, but that there is a tendency for a higher incidence of brain necrosis with PT. Publication and analysis of further studies is needed to validate these findings. [ABSTRACT FROM AUTHOR]

Loss-of-function mutations in the Breast Cancer Susceptibility Gene (BRCA1 and BRCA2) are often detected in patients with breast cancer. Poly(ADP-ribose) polymerase-1 (PARP1) plays a key role in the repair of DNA strand breaks, and PARP inhibitors have been shown to induce highly selective killing of BRCA1/2-deficient tumor cells, a mechanism termed synthetic lethality. In our previous study, a novel PARP1 inhibitor─( E )-2-(2,3-dibromo-4,5-dimethoxybenzylidene)- N -(4-fluorophenyl) hydrazine-1-carbothioamide (4F-DDC)─was synthesized, which significantly inhibited PARP1 activity with an IC 50 value of 82 ± 9 nM. The current study aimed to explore the mechanism(s) underlying the antitumor activity of 4F-DDC under in vivo and in vitro conditions. 4F-DDC was found to selectively inhibit the proliferation of BRCA mutant cells, with highly potent effects on HCC-1937 (BRCA1 -/- ) cells. Furthermore, 4F-DDC was found to induce apoptosis and G2/M cell cycle arrest in HCC-1937 cells. Interestingly, immunofluorescence and Western blot results showed that 4F-DDC induced DNA double strand breaks and further activated the cGAS-STING pathway in HCC-1937 cells. In vivo analysis results revealed that 4F-DDC inhibited the growth of HCC-1937-derived tumor xenografts, possibly via the induction of DNA damage and activation of the cGAS-STING pathway. In summary, the current study provides a new perspective on the antitumor mechanism of PARP inhibitors and showcases the therapeutic potential of 4F-DDC in the treatment of breast cancer.