bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2022‒01‒30
six papers selected by
Lara Paracchini
Humanitas Research

  1. Biomark Med. 2022 Feb;16(2): 127-145
      Liquid biopsies have gained an increasing interest in the last years among medical and scientific communities. Indeed, the value of liquid effusions, while less invasive and more accurate techniques, has been markedly highlighted. Peripheral blood comprises the most often analyzed sample, but recent evidences have pointed out the huge importance of other bodily fluids, including pleural and peritoneal fluids, urine, saliva and cerebrospinal fluid in the detection and monitoring of different tumor types. In face to these advances, this review aims to provide an overview of the value of tumor-associated mutations, detectable in different effusions, and how they can be used in clinical practice, namely in prognosis assessment and early disease and minimal disease recurrence detection, and in predicting the treatment response or acquired-resistance development.
    Keywords:  bodily fluids; cancer biomarkers; cancer monitoring; liquid biopsy; tumors
  2. World J Clin Oncol. 2021 Dec 24. 12(12): 1215-1226
      BACKGROUND: The mutation-based analysis of circulating tumor DNA (ctDNA) is a promising diagnostic tool for clinical oncology. However, it has low success rate because many cancer patients do not have detectable ctDNA in the bloodstream.AIM: To evaluate whether preoperative tumor irradiation results in a transient increase of plasma ctDNA concentration due to the induction of apoptosis in radiation-exposed cells.
    METHODS: This study focused on patients with locally advanced rectal cancer, because preoperative tumor irradiation is a part of their standard treatment plan. Nine subjects, whose tumors contained KRAS, NRAS or BRAF mutations, donated serial blood samples 1 h prior to the first fraction of irradiation (at baseline), immediately after the first fraction (time 0), and 1, 3, 6, 12, 24, 36, 48, 72 and 96 h after the first fraction. The amount of mutated gene copies was measured by droplet digital PCR.
    RESULTS: Five out of nine patients were mutation-negative by ctDNA test at baseline; two of these subjects demonstrated an emergence of the mutated DNA copies in the bloodstream within the follow-up period. There were 4 patients, who had detectable ctDNA in the plasma at the start of the experiment; three of them showed an evident treatment-induced increase of the content of mutated RAS/RAF alleles.
    CONCLUSION: Local tumor irradiation may facilitate the detection of tumor-specific DNA in the bloodstream. These data justify further assessment of the clinical feasibility of irradiation-assisted liquid biopsy.
    Keywords:  BRAF; KRAS; Liquid biopsy; Mutations; Radiotherapy; Rectal cancer; Tumor response
  3. World J Surg Oncol. 2022 Jan 22. 20(1): 21
      BACKGROUND: Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis.METHODS: Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets.
    RESULTS: Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data.
    CONCLUSIONS: MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.
    Keywords:  Biomarkers; Colorectal cancer; MeDIP-seq; cfDNA
  4. Nat Rev Clin Oncol. 2022 Jan 26.
      The development of immune-checkpoint inhibitors (ICIs) has heralded a new era in cancer treatment, enabling the possibility of long-term survival in patients with metastatic disease, and providing new therapeutic indications in earlier-stage settings. As such, characterizing the long-term implications of receiving ICIs has grown in importance. An abundance of evidence exists describing the acute clinical toxicities of these agents, although chronic effects have not been as well catalogued. Nonetheless, emerging evidence indicates that persistent toxicities might be more common than initially suggested. While generally low-grade, these chronic sequelae can affect the endocrine, rheumatological, pulmonary, neurological and other organ systems. Fatal toxicities also comprise a diverse set of clinical manifestations and can occur in 0.4-1.2% of patients. This risk is a particularly relevant consideration in light of the possibility of long-term survival. Finally, the effects of immune-checkpoint blockade on a diverse range of immune processes, including atherosclerosis, heart failure, neuroinflammation, obesity and hypertension, have not been characterized but remain an important area of research with potential relevance to cancer survivors. In this Review, we describe the current evidence for chronic immune toxicities and the long-term implications of these effects for patients receiving ICIs.