Expert Review of Anticancer Therapy最新文献

Areas covered: Here we describe novel agents, their mechanism(s) of action, preclinical results, and ongoing clinical trials in HNSCC.

Expert opinion: Established therapeutic targets in HNSCC include EGFR (cetuximab) and PD-1 (pembrolizumab and nivolumab). Despite the detection of many other possible targets in HNSCC cell lines and patient tumors, no other therapies have successfully advanced to date. Identification of predictive biomarkers may guide the use of targeted agents and combination therapies. Clinical trials supported by strong preclinical data in relevant models are more likely to advance treatment options.

Introduction: Cancer constitutes the greatest public health threat to humans, as its incidence and mortality rates continue to increase worldwide. With the development of medical physics, more practitioners focus on the direct and indirect anti-tumor effects of physical factors. Infrared radiation (INR) is currently the most rapidly developing physical therapy method for tumors and has become a favored target for many oncologists and researchers owing to its advantages of high efficiency, low toxicity, and strong feasibility.

Areas covered: This work provides a comprehensive collection of the latest information on INR anti-tumor research, drawing from public medical databases (PubMed, Web of Science, Embase, and Clinical Trials) from the last 10 years (2014 to 2024), and encompassing both basic and clinical research in oncology and physics. This article reviews the application of INR in tumor hyperthermia, summarizes and analyzes the practical value of INR for tumor treatment, and discusses future development trends to provide valuable assistance for the subsequent development of oncology.

Expert opinion: Currently, INR has continuously accumulated excellent data in the field of tumor hyperthermia, bringing practical survival benefits to patients with cancer, and playing an important role in basic and clinical cancer research.

Purpose: To evaluate the diagnostic accuracy of diffusion tensor imaging (DTI)-derived metrics mean diffusivity (MD) and fractional anisotropy (FA) in differentiating glioma recurrence from pseudoprogression.

Methods: The Cochrane Library, Scopus, PubMed, and the Web of Science were systematically searched. Study selection and data extraction were done by two investigators independently. The quality assessment of diagnostic accuracy studies was applied to evaluate the quality of the included studies. Combined sensitivity (SEN) and specificity (SPE) and the area under the summary receiver operating characteristic curve (SROC) with the 95% confidence interval (CI) were calculated.

Results: Seven high-quality studies involving 246 patients were included. Quantitative synthesis of studies showed that the pooled SEN and SPE for MD were 0.81 (95% CI 0.70-0.88) and 0.82 (95% CI 0.70-0.90), respectively, and the value of the area under the SROC curve was 0.88 (95% CI 0.85-0.91). The pooled SEN and SPE for FA were 0.74 (95% CI 0.65-0.82) and 0.79 (95% CI 0.66-0.88), respectively, and the value of the area under the SROC curve was 0.84 (95% CI 0.80-0.87).

Conclusions: This meta-analysis showed that both MD and FA have a high diagnostic accuracy in differentiating glioma recurrence from pseudoprogression.

Registration: PROSPERO protocol: CRD42024501146.

Introduction: Until recently, the available human receptor epidermal growth factor 2 (HER2) targeted agents were ineffective for treating patients with HER2-low expressing breast cancer (defined as immunohistochemical expression of 1+ or 2+ without amplification). The development of novel and potent HER2-directed antibody-drug conjugates, affective at treating HER2-low expressing breast cancers, have changed the way we think about HER2-low expression and expanded the treatment options for many patients with advanced disease.

Areas covered: In this review, we summarize the current management of HER2-low breast cancer and commonly encountered challenges such as treatment sequencing and toxicity management.

Expert opinion: trastuzumab deruxtecan (T-DXd) is a treatment option for patients with advanced, HER2-low breast cancer, irrespective of the hormone receptor status. The current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer; however, other agents are available in this setting and risks and benefits for each should be considered in shared decision making. Up to 10-15% of patients receiving T-DXd develop interstitial lung disease. Patient and clinician education are key to safely implement T-DXd in clinical practice.

Background: Previous studies have revealed the importance of CYFRA 21-1 in the diagnosis of oral squamous cell cancer (OSCC). However, the results are inconsistent. This meta-analysis is to evaluate CYFRA 21-1's efficacy in distinguishing OSCC.

Methods: Systematic searches of Web of Science, PubMed, and CNKI (1996-2024) were conducted following the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Results: Analysis of 693 patients and 548 controls yielded combined sensitivity (SEN) of 0.71 (95% CI: 0.68, 0.75), specificity (SPE) of 0.88 (95% CI: 0.85, 0.90), and area under the curve (AUC) of 0.927. Subgroup analysis showed higher SEN (0.88), SPE (0.93), and AUC (0.962) in saliva versus serum. Enzyme-linked immunosorbent assay (ELISA) demonstrated superior performance over electrochemiluminescent immunoassay (ECLIA) (AUC: 0.968 vs. 0.868).

Conclusion: CYFRA 21-1 is effective in OSCC diagnosis, with ELISA showing better sensitivity. Saliva emerges as a promising diagnostic medium compared to serum.

Registration: PROSPERO CRD42024566835.

Introduction: Advances in our understanding of tumor biology shed light on hallmarks of cancer development and progression that include dysregulated DNA damage repair (DDR) machinery. Leveraging the underlying tumor genomic instability and tumor-specific defects in DDR, Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induced DNA damage emerges as a novel non-chemotherapy therapeutic opportunity. PARPis are currently approved in multiple tumor types, with the largest benefit seen in tumors with homologous recombination repair (HRR) deficiency, including germline and somatic mutations in BRCA1/2 genes (BRCA) and other pathway members such as PALB2 and Rad51c.

Areas covered: This review article summarizes the current approval landscape and known and proposed mechanisms of resistance to PARPi. Further, therapeutic strategies to overcome PARPi resistance are discussed, including ongoing clinical trials.

Expert opinion: PARPi have proven to be a safe and effective therapy and represents a cornerstone treatment across multiple solid tumor types. Elucidating innate and acquired mechanisms of resistance, coupled with the emergence of novel therapeutic options to capitalize on the activity of PARPi and prevent or reverse the acquisition of resistance, provides an opportunity to further expand the role of PARPi in cancer therapy.

Background: Genetic polymorphisms play a crucial role in predicting treatment efficacy in patients with hepatocellular carcinoma (HCC). This study aims to evaluate the response to Transarterial Chemoembolization (TACE) in relation to the genetic polymorphisms of interleukin 28B (IL28B) and angiopoietin-2 (ANGPT2) in HCC patients.

Research design and methods: Prospective cohort study conducted on 104 eligible HCC Egyptian patients who underwent TACE using doxorubicin and lipiodol. Genotyping of the IL28B and ANGPT2 genes was performed with laboratory data analysis.

Results: At baseline IL28B rs12979860 genotypes C/T, C/C and T/T appeared in 43.9%, 34.6% and 21.5% while ANGPT2 rs55633437 genotypes C/C, C/A and A/A found in 71.03%, 28.04% and 0.93% of patients respectively. After one month of therapy, 51.4% of patients achieved a complete response. There was a significant difference in relation to IL28B rs12979860 genotypes (p = 0.017) whereas ANGPT2 rs55633437 genotypes (p = 0.432) showed no significant difference in patient response after one month of TACE.

Conclusion: This study demonstrates the effectiveness of TACE in Egyptian HCC patients, as evidenced by low recurrence rates. Furthermore, the IL28B rs12979860 (C/T) gene may be associated with the efficacy and prognosis of TACE treatment in HCC Egyptian patients.

Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05291338).

In recent years, prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, has emerged as a promising biomarker for theranostics, integrating diagnosis and therapy. PSMA's overexpression in various tumors, including brain metastases and high-grade gliomas, suggests its potential in neuro-oncology. Pruis et al. conducted a proof-of-concept study comparing intra-arterial (IA) and intravenous (IV) administration of ⁶⁸Ga-PSMA-11 in brain tumor patients, aiming to enhance radioligand therapy (RLT) outcomes. Ten patients underwent IV and super-selective IA (ssIA) tracer administration, showing higher tumor uptake and more favorable biodistribution after ssIA administration on positron emission tomography (PET). Dosimetry modeling on the basis of PET data resulted in median absorbed radiation doses per tumor per cycle notably higher with ssIA with respect to IV administration, indicating its potential for RLT optimization. Challenges persist, notably in penetrating intact blood-brain barriers and targeting tumor cells effectively. To overcome these limitations, novel approaches like convection-enhanced delivery and focused ultrasound warrant exploration. Safety concerns, though minimal in this study, underscore the need for larger trials and AI-assisted procedures. PSMA's role in neuro-oncological theranostics is promising, but future research must address specificity and compare it with emerging targets.

Introduction: Although meningiomas are the most common primary brain tumor, there are limited treatment options for recurrent or aggressive lesions. Compared to other brain tumors, meningiomas may be uniquely amenable to immunotherapy by virtue of their location outside the blood-brain barrier.

Areas covered: This review describes our current understanding of the immunology of the meninges, as well as immune cell infiltration and immune signaling in meningioma. Current literature on meningioma immunology and immunotherapy was comprehensively reviewed and summarized by a comprehensive search of MEDLINE (1/1/1990-6/1/2024). Further, we describe the current state of immunotherapeutic approaches, as well as potential future targets. Potential immunotherapeutic approaches include immune checkpoint inhibition, CAR-T approaches, tumor vaccine therapy, and immunogenic molecular markers.

Expert opinion: Meningioma immunotherapy is in early stages, as no immunotherapies are currently included in treatment guidelines. There is substantial heterogeneity in immune cell infiltration, immunogenicity, and immune escape across tumors, even within tumor grade. Furthering our understanding of meningioma immunology and tumor classification will allow for careful selection of tumors and patient populations that may benefit from primary or adjunctive immunotherapy for meningioma.