Current Opinion in Oncology最新文献

Purpose of review: The introduction of immune checkpoint inhibitors (ICI) in advanced sarcoma has been largely disappointing due to their "cold" tumor microenvironment, characterized by low tumor mutational burden, scarce CD8 + T-cell infiltration, and minimal expression of PD-1/PD-L1. However, recent findings highlight several scenarios in which immune checkpoint blockade exhibits clinical efficacy.

Recent findings: ICIs have shown durable efficacy in specific sarcoma subtypes, such as alveolar soft part sarcoma (ASPS), with objective response rates (ORR) exceeding 35% and 50%, in monotherapy or in combination, respectively. Doxorubicin-based regimens plus ICIs have yielded notorious and higher ORRs in the most common sarcoma subtypes, than historical chemotherapy data. Neoadjuvant radiation therapy combined with ICIs has significantly improved disease-free survival in localized selected soft tissue sarcomas.

Summary: Immunotherapy targeting immune checkpoints in sarcomas is evolving, with recent findings highlighting its potential. Single-arm trials underscore the efficacy of ICIs in rare sarcomas, exemplified by the FDA approval of atezolizumab for ASPS. Combination strategies are proving more effective than chemotherapy alone, with ongoing comparative studies assessing chemo-immunotherapy in both metastatic and localized sarcomas. Advances in predictive biomarkers could expand the clinical use of ICIs.

Purpose of review: Patients with HPV-related oropharyngeal cancer have very good survival outcomes but a high burden of toxicity. This has led to significant efforts to attempt to use a variety of biomarkers to select patients who are candidates for de-escalated treatment.

Recent findings: Initially, the field used HPV status alone as a biomarker to select patients with oropharyngeal cancer for de-escalation, however, the recently presented results of NRG Oncology HN005 showed that this is an insufficient strategy to select patients for potential de-escalation as patients in that study who received 60 Gy rather than the standard 70 Gy of radiation had diminished progression-free survival. This has led to a myriad of other strategies to potentially identify patients who may be able to receive less intense treatment but maintain a high rate of cure.

Summary: Many biomarker options exist to try and select patients for potential treatment de-escalation. We anxiously await the results of multiple ongoing phase II studies regarding many of these biomarkers and believe that the future of treatment for oropharyngeal cancer will be significantly more personalized.

Purpose of review: In the era of precision medicine, the introduction of FDA-approved prostate-specific membrane antigen (PSMA) targeting tracers has revolutionized prostate cancer imaging. These tracers enable functional positron emission tomography (PET) imaging, allowing for precise identification of the location and extent of prostate cancer spread. This review serves as a practical guide for multidisciplinary teams caring for prostate cancer patients, outlining the current approved uses of PET imaging with PSMA tracers and exploring its future applications.

Recent findings: PSMA PET/CT has become a reliable modality for initial staging in patients with intermediate-to-high risk prostate cancer, restaging in cases of biochemical recurrence and further clarifying disease status among patients with conventional imaging based nonmetastatic castrate resistant prostate cancer and metastatic prostate cancer. Additionally, it has promising roles in selecting patients for radioligand therapy, monitoring treatment response, and guiding therapeutic decision-making.

Summary: PSMA PET/CT is currently a crucial imaging tool used at key stages of prostate cancer management, with ongoing research exploring its potential for additional clinical applications.

Purpose of review: This review examines the existing literature on metabolic pathways associated with bladder cancer (BC) and investigates four domains: (1) diagnoses, (2) cancer classification (staging & grading), (3) tracking, and (4) treatment.

Recent findings: A systematic search of relevant databases identified studies meeting predefined inclusion criteria. A diverse array of metabolic pathways was found to hold significant biological and clinical relevance to BC, with particular emphasis on amino acid (AA), lipid, nucleic acid (NA), and bioenergetic pathways. Recent studies have elucidated utilities for metabolomics in diagnosis of BC, staging and grading the disease, monitoring progression or recurrence, and informing treatment strategies. Specifically, fatty acids were observed to be upregulated by as much as 90-fold in studies focused on BC diagnosis, alongside the upregulation of AA metabolites. Metabolites such as AA, lipids, and aldehydes showed potential as diagnostic biomarkers for BC. NA metabolites were particularly effective in monitoring BC status postsurgical resection. Furthermore, metabolites from lipid, bioenergetic, and AA pathways demonstrated utility in predicting tumor cell sensitivity to chemotherapy.

Summary: A broad spectrum of metabolic pathways and metabolites offers significant potential for applications in the diagnosis, staging, monitoring, and treatment of BC. These findings underscore the promise of metabolomics as a valuable tool in improving BC management and patient outcomes.

Purpose of review: Genomic and transcriptomic sequencing technologies have revolutionized our ability to characterize prostate cancer at the molecular level. The underlying premise of next-generation sequencing technologies and their current and evolving applications in prostate cancer management are provided in the review.

Recent findings: Improved methodologies are allowing timely sequencing of the coding regions or both the coding and noncoding regions of the genome to help identify potential mutations and structural variations in the prostate cancer genome, some of which are currently also targetable therapeutically. DNA microarray- based differential gene expression has been supplanted by RNA sequencing (RNA-seq), which not only allows for more accurate quantitation but also nucleotide-level resolution to investigate the entire transcriptome, including alternative gene spliced transcripts and noncoding RNA transcripts, whose full clinical implications have yet to be fully understood and realized. Gene classifier platforms that predict risk of recurrence or metastasis are being incorporated into prostate cancer management algorithms. In the appropriate clinical context, not only somatic but also germline mutation testing is being recommended.

Summary: Continued clinical integration of sequencing technologies and ongoing research will lead to improved understanding of prostate cancer biology and prostate cancer treatment.

Purpose of review: This review is designed to highlight recent research focused on improving outcomes in men with advanced prostate cancer.

Recent findings: Recent randomized trials have suggested advantages to treating men with advanced prostate cancer earlier in their disease course with novel hormonal agents and in some cases chemotherapy. Work remains to identify the optimal sequence of systemic therapies for metastatic prostate cancer with a focus on biomarkers that might select men in need of novel therapeutics. Some men with oligometastatic disease may benefit from localized therapy to sites of isolated progression and research continues to focus on optimally selecting these men. Radiopharmaceuticals are changing the treatment paradigm in advanced prostate cancer with efforts ongoing to improve outcomes with better biomarkers for response and novel treatment combinations.

Summary: Ongoing research focuses on refining the use of existing therapeutics and developing novel treatments and combinations for men with advanced prostate cancer.

Purpose of review: Normal and malignant prostate engage in high rates of de novo polyamine synthesis. This review considers how polyamine metabolism regulates prostate cancer initiation and progression.

Recent findings: The androgen receptor (AR) establishes a metabolic program to drive robust polyamine synthesis in the normal prostate. Upon malignant transformation, this AR-driven metabolic program persists and is optimized for oncogenesis by the proto-oncogene MYC and/or alterations to PI3K signaling. A deeper understanding of the function of polyamines in prostate cancer may be obtained by considering their function in the normal prostate.

Summary: Recent findings support ongoing research into the role of polyamines in driving prostate cancer initiation and progression and suggest targeting polyamine metabolism remains a promising therapeutic strategy for prevention and treatment of prostate cancer.

Purpose of review: Rare cancers of the genitourinary (GU) tract are often clinically aggressive yet have few or no standard-of-care treatments. Multiple antibody-drug conjugates (ADCs) have been approved in solid malignancies. This review explores the use of ADCs in rare GU tumors in the context of biological pathways and ongoing research in solid tumors.

Recent findings: Few clinical trials of ADCs focus on recruiting participants with rare tumors of the GU tract, including trials testing enfortumab vedotin as monotherapy or combined with pembrolizumab, and sacituzumab govitecan as monotherapy or combined with atezolizumab. We highlight many ongoing trials of novel ADCs for advanced/metastatic solid tumors and emphasize the potential eligibility of patients with rare GU tumors for tumor-agnostic trials.

Summary: ADCs are being tested in multiple solid tumors, including rare GU tumors. Ongoing preclinical research supports the use of some ADCs in several rare GU tumors and improves our understanding of their pathophysiology.

Purpose of review: Relapsed or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a deadly disease that historically was treated with palliative chemotherapy-based regimens. Since 2019, immunotherapy-based regimens have become the standard of care for 1 st line treatment in this disease. Over the last several years, there have been numerous studies conducted with novel combination therapies for R/M HNSCC but there has not yet been a new standard of care.

Recent findings: Novel treatment combinations with chemotherapy, targeted therapy, immunotherapy, vaccines, and intratumoral drugs have been evaluated in the treatment of R/M HNSCC. Favorable efficacy has been seen with many of these combinations, although some large studies have failed to improve upon the current standard.

Summary: Many promising combination regimens are being tested which could lead to a new standard of care in the treatment of R/M HNSCC in the coming years.