• Berzosertib plus gemcitabine was well tolerated in 38 patients with advanced NSCLC. • Preliminary signs of clinical efficacy were observed. • Response rate was numerically increased in patients with high TMB and LOH scores. • Potential DDRi biomarkers should be investigated in genomically selected patients. • Berzosertib plus chemotherapy is being investigated in other treatment settings.

Recent studies have reported several beneficial effects of natural compounds on cancerous cells, highlighting their use for future treatments. These preliminary findings have encouraged experiments with natural substances, such as plant extracts, to examine both cytotoxic and mitogenic effects and find alternative treatments for diseases such as breast cancer. This study examines the effects of microwave-assisted and ethanol maceration of marjoram (Origanum majorana) on MCF-7 breast cancer cell lines and normal breast tissue cell lines used as controls. Marjoram extracts displayed a cytotoxic effect on the MCF-7 cell lines and a mitogenic effect on the control cell lines at the MTS test. The metabolic profiles of MCF-7 and control cell lines were also assessed using the Biolog Phenotype Mammalian Metabolic (PM-M) platform and revealed statistically significant differences in the utilization of energy sources, metabolic activity in the presence of certain ionic species, and responses to metabolic effectors, such as stimulant/catabolic compounds and steroid hormones. Exposure to marjoram extracts exerted positive effects on the MCF-7 cells on the abnormal utilization of energy sources and the responses to metabolic effectors, while no major effects were detected on control cells. These effects were compared to the metabolic impact of the chemotherapeutic agent doxorubicin, which showed profound cytotoxic effects on both cancerous and normal breast cells. In conclusion, our in vitro evidence indicates that marjoram extracts are a promising alternative to chemotherapy in breast cancer since they can successfully eliminate cancerous cells by affecting their metabolic capacity to proliferate without inducing noticeable adverse effects on normal breast tissue.

Background: Circulating tumor (ct)DNA is a prognostic biomarker in gastrointestinal malignancies. In rectal cancer, its utility to inform perioperative management and predict recurrence, particularly in patients undergoing non-operative management (NOM), remains unclear. Studies are needed to clarify how post-neoadjuvant therapy (NAT) and post-surgical ctDNA status correlate with clinical outcomes in localized rectal cancer. Methods: We retrospectively analyzed ctDNA data from 220 patients with rectal cancer using a personalized tumor-informed assay (Signatera™, Natera, Inc., Austin, TX, USA). Of these, 148 (67.3%) underwent NAT followed by surgery, and 72 (32.7%) underwent NAT followed by NOM. We assessed associations between post-NAT ctDNA status and survival outcomes. In the surgical cohort, we examined associations between post-operative ctDNA status and clinical response, pathological response, survival outcomes, and NAR scores. Results: In the surgical cohort, ctDNA positivity at the post-operative MRD timepoint was a strong predictor of recurrence, with an 88.3% relapse rate compared to 11.5% in ctDNA-negative patients (p < 0.001). Among the 64 NOM patients with post-NAT ctDNA, 21.9% (14/64) were ctDNA-positive, of whom 100% (14/14) relapsed (92.9% local-only), 13 relapsed by the time of data cut-off, and one relapsed 8 months after the cut-off. Only 10% (5/50) of the ctDNA-negative NOM patients experienced local recurrence (p < 0.0001). ctDNA positivity post-NAT was associated with inferior DFS (p = 0.003). Conclusion: ctDNA was a strong predictor of recurrence in rectal cancer, including in NOM settings. In NOM patients, ctDNA detected local recurrences, highlighting its potential to guide post-NAT surveillance and treatment.

Background/Objectives: Breast cancer is a prevalent and heterogeneous disease with multiple subtypes, which are defined by characteristics such as molecular biomarkers and metastatic status. This study aimed to profile the metabolic activity of various breast cancer subtypes, both with and without chemotherapy (doxorubicin) application. Methods: Six human breast cell lines were evaluated, two non-tumorigenic controls and four cancerous lines. The cancer lines were clustered as primary-derived, metastasis-derived, triple-negative (TNBC), and strong hormone receptor-positive (ER+/PR+) and analyzed using the Biolog phenotype mammalian microarrays (PM-M1 to PM-M8) to assess metabolic activity via NADH production under a wide array of substrate parameters. Results: Unique metabolic profiles emerged across the subtypes and clusters; the TNBC and metastatic cells demonstrated enhanced utilization of glycolytic and anaerobic substrates consistent with the Warburg effect. The ER+/PR+ cells showed heightened glucose utilization and unique sensitivity to metabolic effectors and doxorubicin. Additionally, significant metabolic differences were observed in nucleoside and amino acid utilization between cancer and control cells, particularly in metastatic and TNBC lines. Conclusions: Our findings reveal the profound metabolic diversity among breast cancer subtypes and highlight distinct substrate dependencies for proliferation. The results additionally provide a framework for developing metabolic biomarkers and targeted therapies for chemotherapy resistance in breast cancer subtypes.