Mutations in the oncogene p53 are present in nearly all types of carcinomas and are commonly inactivated in certain tumor types, resulting in a poor prognosis for these patients. In contrast to the prevailing perspective that targeting p53 protein is not feasible, an increasing number of scholars have found that strategies such as directly or indirectly targeting P53 to enhance or restore the function of wild-type P53, or degrading mutant P53 so that the gain of function caused by it disappears, as well as modulating the immune response and cellular metabolism, can control the progression of tumor cells in different states of P53. This article aims to provide a comprehensive overview of the most recent targeted drugs for solid tumors with different P53 status. At the same time, it conducts a thorough analysis of the efficacy of relevant drugs in patients and puts forward possible reasons for the poor efficacy of some medicines.

Depressive symptoms are recognized contributors to breast cancer progression; while previous studies have investigated the role of antidepressants in breast cancer, their therapeutic potential remains insufficiently and systematically explored. This study systematically evaluated the anti-tumor efficacy of six clinically used antidepressants (escitalopram, amitriptyline, fluoxetine, paroxetine, desvenlafaxine, and duloxetine) in 4T1 (murine triple negative) and MCF-7 (human ER⁺/HER2^-) breast cancer cells. The results indicated that duloxetine exhibited the most potent cytotoxicity, with IC₅₀ values of 6.94 μM in 4T1 and 16.16 μM in MCF-7 cells. Although less potent than docetaxel, duloxetine still exhibited significant anti-proliferative, anti-migratory, and pro-apoptotic effects. In vivo, duloxetine (10-30 mg/kg) significantly suppressed tumor growth in 4T1-bearing mice, accompanied by decreased Ki-67 expression and increased E-cadherin. Moreover, duloxetine significantly inhibited the phosphorylation of AKT and mTOR, thereby promoting autophagy activation, as evidenced by increased LC3 expression and decreased P62 levels. Additionally, duloxetine promotes apoptosis by upregulating Bax and downregulating Bcl-2 expression both in vitro and in vivo. These findings reveal that duloxetine exerts anti-breast cancer effects through inhibiting AKT/mTOR signaling and promoting Bax/Bcl-2-mediated apoptosis, highlighting its potential for therapeutic repurposing as an adjunct treatment-particularly, in breast cancer patients with coexisting depression.

Breast cancer is a worldwide serious health issue with constantly recurring issues of drug resistance, toxicity, and recurrence. These limitations have prompted research on various drug compounds, particularly those derived from plants. Quercetin is one such compound, a flavonol dietary component. This review aims to synthesize the existing evidence on the molecular pathways through which quercetin regulates various oncogenic cascades in breast cancer, including the PI3K/Akt/mTOR, Wnt/β-catenin, JAK/STAT, AMPK, and non-coding RNA pathways. The review also highlights the therapeutic potential of quercetin to potentiate the efficacy of conventional chemotherapies and suppress drug resistance and thus suggests the potential of quercetin as a combinational therapy agent. In contrast to previous reviews, this study presents a new and up-to-date description of the pleiotropic effects of quercetin in breast cancer pathobiology, bridging mechanistic understanding with translational applicability.

Natural bioactive compounds have demonstrated potential in altering the Notch signaling system, a crucial regulator of cancer development. This review discusses the molecular interactions of various substances such as flavonoids, polyphenols, terpenoids, and alkaloids with ligands, receptors, and downstream effectors. Terpenoids like curcumin can combat Notch-mediated medication resistance, while flavonoids like quercetin prevent Notch receptor activation. Alkaloids that directly or indirectly modulate Notch signaling have anticancer effects. Preclinical and clinical investigations have demonstrated the effectiveness of several of these drugs, and several have progressed to clinical trials. The review emphasizes clinical trials to optimize the pharmacokinetics, safety, and therapeutic potential of natural medicines for cancer treatment. Natural bioactive substances targeting the Notch signaling system have the potential to develop cancer treatment. These treatments provide a potential alternative or supplement to current treatments due to their more targeted and less toxic approach to cancer cells. Natural bioactive compounds require further research to enhance pharmacokinetics, investigate processes, and conduct clinical trials.

Surveillance after colorectal cancer (CRC) resection is an important aspect of survivorship care. This study aimed to assess whether there were any changes to post-operative surveillance uptake in non-metastatic CRC patients and pre- and post-COVID pandemic in Victoria.

All CRC patients (Stages I-III) who underwent curative surgery at Western Health, Victoria, Australia, were included. Surveillance included a three-monthly clinical review and carcinoembryonic antigen (CEA) up to 18 months and CT imaging and colonoscopy at 12 months following surgical resection.

Between 2019 and 2022, 380 patients were identified. Stage III patients had the highest uptake with regard to clinical reviews, CEA testing and 12-month CT (83.3%, 60.3% and 85.5%, respectively) while Stage I patients had the lowest (52.7%, 35.7% and 75.5% respectively) (p < 0.05). Colonoscopy surveillance was low regardless of stage (66.3%, 59.8% and 59.7% of Stages I, II and III, respectively). Uptake of CEA, clinic reviews and colonoscopy did not vary during our study period. More patients underwent 12-month CT following the COVID pandemic (87%) compared to pre-COVID (73.1%) or during COVID (76%, p < 0.05). There was no difference in 18-month mortality and overall recurrence during our study timelines.

Lower-stage CRC patients had lower rates of surveillance uptake, in particular, with CEA blood tests and colonoscopy. Survivorship provision did not change pre- or post-COVID.

Recovery of endogenous testosterone following androgen deprivation therapy (ADT) for prostate cancer is uncertain.

To prospectively evaluate testosterone (T) recovery rates and timing after neoadjuvant ADT followed by radical prostatectomy (RP).

We report a secondary analysis from a phase II randomized trial involving 64 patients who received a 3-month neoadjuvant ADT regimen (goserelin, abiraterone with prednisone and for half of the participants, apalutamide) followed by RP. Total Testosterone (TT) was measured at baseline, during ADT (3 m), and after 4, 8, and 12 months post-ADT cessation. Return to non-castrate levels (TT > 50 ng/dL), to normal (TT ≥ 300 ng/dL), and back to baseline level (BTB, defined as TT ≥ baseline) are reported. Predictive factors were analyzed using uni and multivariate analyses (MVA), and quality of life (QoL) was assessed with the validated Expanded Prostate Cancer Index Composite (EPIC-50).

Chance and chronology of T recovery 1 year after ADT cessation.

Median T levels were as follows: baseline 442 ng/dL (IQR: 321-505); 4 months post-ADT, 144 ng/dL (IQR: 35-284); 8 months, 316 ng/dL (IQR: 243-438); and 12 months, 358 ng/dL (IQR: 285-477). By 12 months, 98.1% of patients reached non-castrate levels, 79.5% returned to normal, and 33.9% to BTB. Half of the patients achieved T > 50 ng/dL in 5 months, T ≥ 300 ng/dL in 9.1 months, and BTB in 13.1 months. In MVA, baseline T was the only significant predictor for T normalization (OR: 1.015; P < .01), while age and baseline T were predictors for BTB recovery (OR for age: 0.88; P = .02; OR for baseline T: 0.99; P = .02). QoL assessment showed persistently low sexual function, with minor improvements over time (median scores: 0 [0-5.6] at 4 months and 2.8 [0-29.2] at 12 months, P < .01), while sexual bother starts very low but significantly increases during follow up (median scores: 100 [IQR: 42.2-100] at 4 months to 50 [IQR: 0-100] at 12 months, P = .03).

Long-term lower T levels can occur even after short-term ADT, persisting longer than anticipated. Clinicians should consider this in patient management.

Our strengths include the prospective, controlled design and a rarely reported ADT triple therapy followed by RP. Limitations include the use of immunoassay to measure TT.

After 3 months of neoadjuvant triple ADT and RP, significant recovery to non-castrate and normal T levels is seen in most patients by 1 year; yet, BTB recovery is achieved in only a third. Higher baseline T and younger age predict faster T normalization and BTB recovery, respectively.

Hepatocellular carcinoma (HCC) is a highly aggressive and highly malignant cancer. Glucose metabolic reprogramming provides sufficient ATP to support HCC's rapid proliferation and invasion. Consequently, this study intends to investigate the effects of FAM99A and FAM99B on glucose metabolic reprogramming, and provide new insights for HCC treatment. Changes in malignant phenotypes and glycolysis-related indices of HCC cells (HCCLM3 and HEPG2) were assessed after exogenous regulation of FAM99A and FAM99B under hypoxic conditions. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glycolytic proton efflux rate (glycoPER) were measured using the Seahorse XF Glycolysis Rate Assay Kit (103344-100, Agilent). HCCLM3 cells were subjected to transcriptome and smallRNA sequencing to identify differentially expressed genes (DEGs) and miRNAs (DE-miRNAs) associated with FAM99A and FAM99B. Under hypoxic conditions, the expression of FAM99A and FAM99B was significantly downregulated in HCC cells. Overexpression of FAM99A or FAM99B significantly inhibited HCC cell proliferation, wound healing, and invasion. Moreover, they effectively decreased intracellular glucose, extracellular lactate, ATP, glycolysis-related enzymes, ECAR, and glycoPER, and increased pH, extracellular glucose, and mitoOCR/glycoPER. A total of 31 DEGs and 15 DE-miRNAs were present in HCCLM3 cells overexpressing FAM99A, and 375 DEGs and 68 DE-miRNAs were identified in HCCLM3 cells overexpressing FAM99B. These DEGs and DE-miRNA targets were involved in cell cycle, apoptosis, metastasis, extracellular matrix remodeling, and metabolic reprogramming. The FAM99B-associated ceRNA network contained one DE-miRNA and 10 DEGs, and their expression differences were consistent with the sequencing results. Hypoxia-induced suppression of FAM99A and FAM99B facilitates proliferation, metastasis, and glucose metabolic reprogramming of HCC.

Male breast cancer (MBC) accounts for less than 1% of all cancers in men, with invasive ductal carcinoma being the most common type. The chemotherapy regimens used for MBC are similar to those for female breast cancer. However, the incidence of chemotherapy-induced complications such as leukocytosis resembling leukemia reaction is not well documented in MBC. This case highlights a rare complication in an MBC patient, induced by prophylactic PEG-rhG-CSF following chemotherapy.

A 51-year-old male with left breast invasive ductal carcinoma underwent modified radical mastectomy. Postoperative pathology revealed high-risk features, and the patient received 8 cycles of chemotherapy with the ddAC-T regimen, followed by PEG-rhG-CSF for febrile neutropenia prevention. After the fifth chemotherapy cycle, the patient developed leukocytosis resembling leukemia reaction, characterized by a white blood cell count exceeding 50 × 10⁹/L, along with intermittent fever up to 42.5°C. The condition was attributed to the PEG-rhG-CSF administration, and the patient was treated with NSAIDs and dexamethasone. Leukocytosis resolved after adjusting the PEG-rhG-CSF dose.

Leukocytosis resembling leukemia reaction induced by PEG-rhG-CSF post-chemotherapy is a rare complication, particularly in MBC patients. This case underscores the importance of careful monitoring and differential diagnosis to avoid misdiagnosis and unnecessary interventions. Personalized treatment strategies and dose adjustments for PEG-rhG-CSF are crucial in managing this rare reaction, emphasizing the need for awareness and individualized care in MBC patients undergoing chemotherapy.

Identifying the genetic signatures in bone and soft tissue tumors enhances our understanding of tumor biology and aids in the subclassification of tumors for personalized treatment. Histone H3.3 alterations play a pivotal role in H3F3A/B K36M-mutant chondroblastomas and H3F3A G34W/L-mutant giant cell tumors of the bone.

In this report, we describe 2 cases of a distinct epithelioid neoplasm with H3F3A K36M mutation but lacking features of chondroblastoma, which extends the spectrum of H3.3-mutant mesenchymal tumors. The 2 cases occurred in pediatric patients, had an aggressive clinical presentation, distinct epithelioid histomorphology with diffuse cytokeratin and TFE3 expression, and identical H3F3A K36M mutations. No gene fusions were identified. Methylation analysis using the DKFZ sarcoma classifier v12.3 pipeline did not classify these tumors with known entities, suggesting the existence of non-chondrogenic mesenchymal tumors within the H3.3-mutant tumor spectrum.

The distinctive histological and molecular features of these 2 cases expand the spectrum of H3.3-mutant tumors and call for further investigation of the biological underpinnings of this group of tumors.

Transcription factors (TFs) play a pivotal role in the development and differentiation of T cells. Recent studies have highlighted unique transcriptional profiles in chimeric antigen receptor T (CAR-T) cells derived from patients with favorable clinical outcomes, suggesting a potential link between TF modulation and improved therapeutic efficacy. Although CAR-T cell therapies have shown some success in treating hematological malignancies, they are limited by challenges such as poor persistence, functional exhaustion, and tumor resistance. To overcome these limitations, researchers have attempted to enhance the efficacy of CAR-T cells through manipulation of TF expression. This Review provides a comprehensive overview of TF engineering in CAR-T cells and elucidates the complex regulatory network between TFs. Notably, modification of basic leucine zipper ATF-like transcription factor in CAR-T cells results in contradictory functional outcomes in different studies. We summarize the potential factors leading to such results and elucidate the importance of setting up a relevant in vitro model to evaluate the effect of TFs on CAR-T cells. In conclusion, this Review highlights the latest advances in TF modifications and proposes strategies for harnessing these insights to empower CAR-T cells with superior antitumor efficacy.