National Cancer Institute-designated cancer centers (NCI-CCs) throughout the United States are mandated to translate state-of-the-art cancer research to communities and enhance clinical care for patients within their catchment areas. NCI-CCs play a vital role in national cancer initiatives focused on optimizing cancer care via personalized medicine in which improved risk assessment, screening, and genetic testing are foundational. In this era of targeted personalized care, although genetics has been incorporated into cancer centers, it is unknown how these innovations are being communicated to the public and communities served on cancer center websites. There is particularly limited knowledge surrounding how NCI-CCs publicly communicate their efforts to integrate patient-reported experiences with genomics to fulfill their overall mission and reduce the cancer burden in their catchment areas.

The objective of this study was to evaluate how NCI-CCs publicly share information on their websites related to cancer center programming and activities to measure and incorporate patients' experiences with the use of genetics to guide cancer care.

For all NCI-CCs providing clinical care (N=65), we conducted a review of publicly available and published information and assessed five domains relevant to patients' experiences with genomic medicine: whether NCI-CCs (1) provided genetic testing, (2) directly expressed a goal of delivering personalized care, (3) provided pharmacogenomic testing, (4) assessed patient-reported experience measures with genomic medicine (including patient-reported outcomes [PROs] and other patient experience measures [OPEMs]), and (5) indicated an established infrastructure or set of resources to evaluate patient experience. We conducted a content analysis of the publicly available websites of NCI-CCs using the validated directed approach to content analysis. We quantified the results of our content analysis using count measures based on a binary (yes or no) coding scheme.

While almost all the NCI-CCs (64/65, 98%) discussed providing personalized care and performing genetic testing on their websites, we found that 58% (38/65) indicated online that they assessed PROs or other patient experience measures with genomic medicine. Fewer centers (25/65, 38%) discussed on their websites having a mechanism for evaluating patients' experiences with genomic medicine that captured broader types of information beyond PROs, such as measures of patient education or care team communication. Finally, approximately 1 in 3 NCI-CCs (23/65, 35%) indicated having an established infrastructure with departmental resources dedicated to monitoring patients' experiences. These centers reflecting a built-in infrastructure were 8% to 12% more likely to publicly communicate targeted activities to assess patients' experiences with genomic medicine.

With the burgeoning use of genomics in research and clinical care, comprehensive evaluation and incorporation of measures of patients' experiences with genomic medicine present a key opportunity to enhance cancer care at NCI-CCs.

Receipt of anthracycline-based chemotherapy and statin therapy have been found to be associated with deterioration of cognitive function in patients with cancer.

To assess the association of statins with attention, verbal fluency, and executive function in patients receiving doxorubicin treatment for cancer.

This secondary analysis of the Preventing Anthracycline Cardiovascular Toxicity With Statins randomized clinical trial, conducted across 31 US community and academic sites from February 5, 2014, through September 24, 2020, involved participants with stage I to IV lymphoma or stage I to III breast cancer undergoing doxorubicin treatment. The data analysis was conducted between August 1, 2024, and April 4, 2025.

Participants were randomized (1:1) to receive a daily 40-mg dose of atorvastatin or placebo before initiating doxorubicin treatment and then continued for 24 months.

Attention, executive function, and verbal fluency were assessed using the Trail Making Test part A (TMT-A) and part B (TMT-B) and the Controlled Oral Word Association test, respectively. Time to complete the assessments were modeled using a linear mixed model, while errors (counts) were modeled using a generalized linear mixed model assuming a Poisson distribution.

A total of 238 participants (mean [SD] age, 49 [12] years; 217 female [91.2%]) were randomized to the statin (n = 118) or placebo (n = 120) groups. Values for TMT-A at 6 and 24 months were similar between the statin group (mean, 32.5 seconds [95% CI, 29.4-35.7 seconds] and 29.8 seconds [95% CI, 26.4-33.2 seconds], respectively) and the placebo group (mean, 28.4 seconds [95% CI, 25.2-31.5 seconds] and 27.8 seconds [95% CI, 24.5-31.0 seconds], respectively). From before treatment to 24 months after treatment, statin recipients had a significant mean improvement of 10.2 seconds for TMT-B (95% CI, 1.9-18.5 seconds), whereas placebo recipients had a nonsignificant improvement of only 0.2 seconds for TMT-B (95% CI, -8.5 to 8.1 seconds). Analysis of the time-by-treatment interaction showed no significant difference between groups. For Controlled Oral Word Association scores in the same period, both the placebo and statin groups showed a mean improvement of 3.62 points (95% CI, 1.71-5.54 points) and 4.74 points (95% CI, 2.69-6.79 points), respectively, with no difference between groups.

This secondary analysis of a randomized clinical trial suggests that the receipt of statins during doxorubicin therapy for lymphoma or breast cancer was not associated with worsening cognitive functions over 24 months. Within-group analyses suggested that statins may have contributed to better executive function on the TMT-B.

ClinicalTrials.gov Identifier: NCT01988571.

Lung cancer (LC) is the most prevalent form of malignant neoplasm globally, as well as the major cause of cancer-related death. Identifying effective pharmaceutical targets is paramount in advancing the development of treatment modalities for LC.

Protein-wide Mendelian randomization (MR) was used in this study. The present study collated data on plasma proteins from a protein quantitative trait loci (pQTL) study with a total of 4907 individuals. Genetic associations with LC were obtained from GWAS, including 3791 cases and 489012 controls. Integration of pQTL and LC genome-wide association study (GWAS) data was employed to identify candidate proteins. MR used single nucleotide polymorphisms (SNPs) as a genetic tool to estimate the causal effect of exposure on the outcome, while reverse Mendelian randomization was performed to assess the presence of false positives. The present study utilized these approaches to evaluate the causal relationship between plasma proteins and LC. Finally, protein-protein interaction (PPI) and functional enrichment analyses were performed to illustrate potential links between proteins and current LC drugs. Finally, drug prediction and molecular docking were performed to predict drugs and explored the expression distribution of key genes by single-cell sequencing.

We identified 46 plasma proteins that are strongly associated with LC Fifteen of these proteins have protective effects. Among them, MMP8(OR = 0.87, 95%CI:0.78-0.97, p = 0.013) had the most significant protective effect. In contrast, 31 proteins increased the risk of LC. IL36A༈OR = 1.20, 95%CI:1.041-1.38, p = 0.012) exhibited the most significant MR result. Notably, COL2A1, MMP19 showed reverse causality. This was further verified by enrichment analysis, which confirmed the causal effect of these proteins. Additionally, the researchers utilized the DSigDB database to predict potentially effective intervening drugs, identifying nine possible candidates. Molecular docking showed that the drugs bind very much to the proteins. KDR and ANGPTL4 are abundantly expressed in lung tissue and are differentially expressed between cells.

The present study has revealed six potential drug targets for the treatment of LC. Drugs designed to target these proteins will be more likely to attain success in clinical trials and are expected to assist in the development of LC drugs and reduce drug development costs.

To evaluate the efficacy and safety of nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with platinum-refractory or intolerant head and neck squamous cell carcinoma (HNSCC) and esophageal squamous cell carcinoma (ESCC).

In this multicenter, phase 2 study (NCT03712397), patients with advanced HNSCC (n = 43) or ESCC (n = 16) who had failed or were intolerant to platinum-based chemotherapy received biweekly nal-IRI 80 mg/m² (equivalent to 70 mg/m² of irinotecan base), LV 400 mg/m², and 5-FU 2400 mg/m² until progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR).

In the intent-to-treat analysis, the ORR and disease control rate were 8.5% and 59.3% for the entire group. In the HNSCC subgroup, ORR and disease control rate were 11.6% and 65.1%, with a median progression-free survival (PFS) of 2.7 months and an overall survival (OS) of 8.1 months. By contrast, no objective responses were observed in ESCC (ORR 0%, disease control rate 43.8%, median OS 4.2 months). The most common grade 3/4 toxicities were lymphopenia (50.8%), neutropenia (42.4%), leukopenia (33.9%), anemia (28.8%), and anorexia (8.5%).

Nal-IRI/5-FU/LV demonstrates modest activity with acceptable safety profiles in patients with platinum-refractory or intolerable advanced HNSCC. The exploratory findings warrant confirmation in larger, randomized studies.

ClinicalTrials.gov: NCT03712397.

Patients with Hodgkin lymphoma (HL) or peripheral T-cell lymphoma (PTCL) who relapse after high-dose chemotherapy (HDCT) have a dismal prognosis. Brentuximab-vedotin (BV) is a CD30-targeting antibody-drug-conjugate (ADC) used in first-line-, salvage-, and maintenance-therapy of HL, as well as first-line- and salvage-therapy of PTCL. In phase I of this trial, we could show that BV can safely be added to BeEAM-HDCT (bendamustine, etoposide, cytarabine and melphalan). Here, we report the randomized phase II part of the trial comparing BV-BeEAM to BeEAM alone (ClinicalTrials.gov: NCT03187210). Primary endpoint was 1-year disease-free survival. Inclusion of 42 patients was planned but the study was terminated early, after a futility analysis showed lack of benefit. Twenty-five patients (HL: 11, PTCL: 14) who were planned to undergo HDCT were included. Median age was 60 years. Patients had a median of two prior therapies, and 11 were previously exposed to BV. Patients in the standard-arm had higher disease stage and (PTCL only) higher IPI. Duration of hospitalization, recovery of neutrophils/platelets, and infections were not significantly different between arms. No treatment related death occurred. However, two patients in the BV-arm developed grade 3 pneumonitis. After 22 months median follow-up, overall response-rate, complete remission-rate, disease-free survival and overall survival did not differ between groups. Pre-planned subgroup-analyses (HL-only, PTCL-only, only those achieving CR) did not show benefit in any subgroup. In conclusion, adding BV to BeEAM does not improve outcomes after HDCT, and may increase pulmonary toxicity. Frequent prior exposure to BV may have limited the potential benefit of the combination.

HCC is a highly lethal cancer characterised by significant sorafenib resistance, leading to poor patient outcomes. Recent studies have suggested that MED8 plays a role in enhancing tumour resistance to drugs, but its role in drug resistance in HCC has not yet been reported. This study found significantly higher MED8 expression in HCC tissues compared to adjacent noncancerous tissues. Increased MED8 expression in HCC correlates with poorer overall survival. Functional assays demonstrated that reduced MED8 expression inhibited HCC cell proliferation and epithelial-mesenchymal transition, promoted apoptosis, and increased sensitivity to sorafenib. Overexpression of MED8 elevated TRIP4 protein levels. TRIP4 overexpression negated the effects of MED8 knockdown, whereas TRIP4 suppression inhibited MED8-driven EMT. Mechanistically, MED8 interacts with TRIP4, reducing its ubiquitination and stabilising TRIP4 protein levels. Our findings indicate that the MED8-TRIP4 axis plays a role in sorafenib resistance in HCC and could serve as a therapeutic target for HCC treatment.

A common mechanism by which cancer cells acquire resistance to chemotherapeutics is through the overexpression of efflux pumps, enabling the removal of cytotoxic agents, such as anthracycline drugs. However, platinum anticancer agents that crosslink DNA and interact with proteins are poor efflux pump substrates. Here, we design dual warhead drug conjugates by tethering a platinum pharmacophore to the doxorubicin backbone. These drug conjugates retain the anticancer activity of anthracyclines and exhibit the ability to both circumvent drug efflux and delay the acquisition of drug resistance. In vivo experiments demonstrate that such drug conjugates extend survival in a preclinical organoid-based model of metastatic colon cancer in mice. Mechanistic studies indicate that these drug conjugates overcome resistance through covalent platinum-protein interactions, leading to significantly improved drug retention and alteration of subcellular drug distribution. This application of platinum offers many opportunities to confront issues related to chemoresistance and alternative pathways for augmenting conventional chemotherapeutics.

Cervicovaginal microbiota dysbiosis has been implicated in the progression of cervical cancer. Recent studies have reported an increased abundance of Porphyromonas species in the vaginal microbiota of cervical cancer patients. Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been associated with adverse pregnancy outcomes and bacterial vaginosis; however, its potential role in the progression of cervical squamous cell carcinoma (CSCC) remains largely unexplored.

We employed immunohistochemistry (IHC), 16S rRNA fluorescence in situ hybridization (FISH), and immunofluorescence to detect P. gingivalis in CSCC tissues. The association between P. gingivalis colonization and CSCC patient survival outcomes was assessed. Transwell and wound healing assays were used to assess the migration and invasion abilities of CSCC cells. In vivo xenograft mouse models were established to evaluate the impact of P. gingivalis on tumor growth and metastasis. Pull-down assays were employed to investigate interactions between the P. gingivalis fimbrial protein FimA and host cell membrane proteins. RNA sequencing and Western blotting were utilized to identify signaling pathways activated by P. gingivalis in host cells.

Porphyromonas gingivalis was detected immunohistochemically in 63% of CSCC tumor tissues, with significantly higher colonization in tumors compared to adjacent nontumor tissues (P < 0.0001). The presence of P. gingivalis was significantly associated with advanced tumor stage (P < 0.01), distant metastasis (P < 0.05), lymph node metastasis (P < 0.01), and poor survival outcomes (P = 0.0257, HR = 3.167) in CSCC patients. P. gingivalis preferentially adhered to CSCC cells and promoted cell migration and invasion. In this study, animal models revealed that P. gingivalis promoted lung and lymph node metastasis in CSCC without affecting tumor growth. Pull-down assays revealed that FimA interacts with CD151 and integrin β1 (ITGB1), which are highly expressed in CSCC cells. Knockdown of CD151 and ITGB1 significantly reduced P. gingivalis adhesion to CSCC cells (P < 0.01) and suppressed its effects on cell migration and invasion (P< 0.05). P. gingivalis treatment activated the JNK/paxillin pathway and triggered actin cytoskeleton reorganization.

This study identifies P. gingivalis as a tumor-associated bacterium that promotes CSCC metastasis through direct interaction between its fimbrial adhesin FimA and the host CD151/ITGB1 complex. This interaction activates JNK/paxillin signaling, induces cytoskeletal reorganization, and enhances the metastatic capacity of CSCC cells. Targeting this microbial-host interaction may provide a novel therapeutic intervention for P. gingivalis-driven CSCC metastasis.

Cold atmospheric plasma (CAP) has demonstrated anti-proliferative activity in various cancer cells, yet its efficacy against drug-resistant cancer cells remains largely unexplored. This study investigates CAP's potential to restore drug sensitivity in fulvestrant-resistant breast cancer cells. Fulvestrant-resistant T47D/fulR and MCF-7/fulR cell lines were developed through 32-week drug exposure. CAP treatment effectively inhibited growth of both resistant cell lines and restored sensitivity to fulvestrant when used as pretreatment. Genome-wide expression analysis revealed that CAP significantly impacts ribosomal and mitochondrial components during resistance acquisition and treatment. The oncogene CCND3 emerged as a key contributor to drug resistance, being highly upregulated in resistant cells but downregulated following CAP treatment. Functional validation through CCND3 knockdown in both resistant cell lines induced increased apoptosis and extended G1 phase, confirming its critical role in resistance mechanisms. These findings demonstrate that CAP can revert fulvestrant-resistant breast cancer cells to a sensitive state by targeting CCND3 and modulating critical cellular pathways, suggesting promising therapeutic potential for overcoming drug resistance in breast cancer treatment.

The development of traditional protein-targeted cancer therapies is a slow and arduous process, often taking years or even decades. In contrast, RNA-based therapies targeting crucial microRNA (miRNA) offer a faster alternative due to the sequence-specific nature of miRNA inhibitor binding. This, combined with the capacity of individual miRNA to influence multiple cellular pathways, makes these small RNA attractive targets for cancer therapy. While miRNA are known to be dysregulated in prostate cancer (PCa), identifying their individual contributions to disease progression and the identification of therapeutically actionable miRNA targets in PCa has been challenging due to limited profiling and lack of screening tools. To address this need, we developed miRKOv2, a miRNA-only CRISPR knockout library enabling systematic, genome-wide loss-of-function screens to identify miRNA essential for PCa cell survival. Our screens uncovered 70 potential essential miRNA candidates, with miR-483 demonstrating the most significant impact on PCa cell viability. Functional characterization revealed that miR-483 disruption potentiated apoptosis in PCa cell lines. Mechanistically, we uncovered a novel regulatory axis wherein miR-483-3p directly modulates a BCLAF1/PUMA/BAK1 apoptotic signaling network, highlighting its critical role in maintaining PCa cell survival. Our findings provide novel insights into the complex regulatory role of miRNA in PCa progression and offer a potential therapeutic strategy for targeting miRNA-mediated pathways in metastatic disease.