Recent Progress of Copper-Based Nanomaterials in Tumor-Targeted Photothermal Therapy/Photodynamic Therapy.

Nanotechnology, an emerging and promising therapeutic tool, may improve the effectiveness of phototherapy (PT) in antitumor therapy because of the development of nanomaterials (NMs) with light-absorbing properties. The tumor-targeted PTs, such as photothermal therapy (PTT) and photodynamic therapy (PDT), transform light energy into heat and produce reactive oxygen species (ROS) that accumulate at the tumor site. The increase in ROS levels induces oxidative stress (OS) during carcinogenesis and disease development. Because of the localized surface plasmon resonance (LSPR) feature of copper (Cu), a vital trace element in the human body, Cu-based NMs can exhibit good near-infrared (NIR) absorption and excellent photothermal properties. In the tumor microenvironment (TME), Cu2+ combines with H2O2 to produce O2 that is reduced to Cu1+ by glutathione (GSH), causing a Fenton-like reaction that reduces tumor hypoxia and simultaneously generates ROS to eliminate tumor cells in conjunction with PTT/PDT. Compared with other therapeutic modalities, PTT/PDT can precisely target tumor location to kill tumor cells. Moreover, multiple treatment modalities can be combined with PTT/PDT to treat a tumor using Cu-based NMs. Herein, we reviewed and briefly summarized the mechanisms of actions of tumor-targeted PTT/PDT and the role of Cu, generated from Cu-based NMs, in PTs. Furthermore, we described the Cu-based NMs used in PTT/PDT applications.

Recent Advances in Cancer Therapeutic Copper-Based Nanomaterials for Antitumor Therapy.

Copper serves as a vital microelement which is widely present in the biosystem, functioning as multi-enzyme active site, including oxidative stress, lipid oxidation and energy metabolism, where oxidation and reduction characteristics are both beneficial and lethal to cells. Since tumor tissue has a higher demand for copper and is more susceptible to copper homeostasis, copper may modulate cancer cell survival through reactive oxygen species (ROS) excessive accumulation, proteasome inhibition and anti-angiogenesis. Therefore, intracellular copper has attracted great interest that multifunctional copper-based nanomaterials can be exploited in cancer diagnostics and antitumor therapy. Therefore, this review explains the potential mechanisms of copper-associated cell death and investigates the effectiveness of multifunctional copper-based biomaterials in the field of antitumor therapy.

Comprehensive Next-Generation Sequencing Reveals Novel Predictive Biomarkers of Recurrence and Thoracic Toxicity Risks After Chemoradiation Therapy in Limited Stage Small Cell Lung Cancer.

PURPOSE: Although definitive chemoradiation therapy (dCRT) remains the most effective treatment modality in limited stage small cell lung cancer (SCLC), some patients progress quickly or develop serious radiation-induced thoracic toxicity (RITT). Molecular correlates of response to dCRT remain to be explored. METHODS AND MATERIALS: Genomic profiling was performed retrospectively on 231 patients with limited-stage SCLC treated with dCRT between 2015 and 2019 using a customized panel covering cancer and radiation therapy response-related genes. Exploratory associations of progression-free survival, overall survival, and RITT with clinical features, tumor genetics, genomic and molecular pathway alterations, and single nucleotide polymorphisms were conducted. RESULTS: In addition to the common SCLC genes, such as TP53, RB1, and NOTCH1/2, potentially actionable mutations in EGFR, KRAS, and BRCA1/2 were among the top alterations in the cohort. At the single-gene level, CDK4 and GATA6 alterations were independent predictors of poor survival by multivariate analysis. At the genomic level, high tumor mutational burden was strongly associated with favorable survival outcome. Pathway-level analysis showed that activating mutations in the MAPK/ERK pathway genes, particularly those in EGFR/ERBB2, correlated with poor survival. Combined analysis enabled optimized risk stratification of post-dCRT survival. On the other hand, our study also confirmed that single nucleotide polymorphisms in MTHFR, CYP2B6, NQO1, and LIG4 were risk alleles of high-grade RITT. Remarkably, somatic loss-of-function mutations in the DNA damage repair pathway genes were associated with increased risk of high-grade RITT, particularly pneumonitis, which likely reflect a complex interplay between the tumor and its immune microenvironment. CONCLUSIONS: Taken together, by examining the mutational landscape of a large cohort of limited-stage SCLC, we identified novel molecular predictors of survival and RITT. Our findings also implicate several key molecular pathways, including the MAPK/ERK and DNA damage repair pathways, in the regulation of dCRT response.

Non-Peutz-Jeghers syndrome-associated ovarian sex cord tumor with annular tubules treated by radiotherapy: a case report and literature review.

There are no standard treatment options for metastatic and recurrent non-Peutz-Jeghers syndrome (PJS)-associated sex cord tumor with annular tubules (SCTAT). The effects of chemotherapy and/or radiotherapy are still not well-defined. Herein, we present a case of a metastatic and recurrent non-PJS-associated SCTAT showing high serum estradiol and progesterone concentrations after surgery and chemotherapy. Radiotherapy (50 Gy/25 fractions) triggered a sharp reduction in the sizes of the metastatic and recurrent masses, and estradiol and progesterone concentrations. Accordingly, we consider that radiotherapy might be effective and safe for metastatic and recurrent SCTAT. The roles of radiotherapy in non-PJS SCTAT should be further validated in large-scale prospective clinical trials.