Evidence map›Paper›PMID 33731038›Full record

ArticleBMC cancer2021

Usefulness of monitoring circulating tumor cells as a therapeutic biomarker in melanoma with BRAF mutation.

Yukiko Kiniwa, Kenta Nakamura, Asuka Mikoshiba, Atsuko Ashida, Yasuyuki Akiyama, Atsushi Morimoto, Ryuhei Okuyama

Abstract read
In one paragraph

Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Metastatic Melanoma: Liquid Biopsy as a New Precision Medicine Approach.International journal of molecular sciences · 2023
    Review
  15. Article
  16. Article
  17. Review
  18. Circulating tumor cells: biology and clinical significance.Signal transduction and targeted therapy · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Yukiko KiniwaDepartment of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Kenta NakamuraDepartment of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Asuka MikoshibaDepartment of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Atsuko AshidaDepartment of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
Yasuyuki AkiyamaLife Science Research Laboratory, Tosoh Corporation, Ayase, Kanagawa, Japan.
Atsushi MorimotoLife Science Research Laboratory, Tosoh Corporation, Ayase, Kanagawa, Japan.
Ryuhei OkuyamaDepartment of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. rokuyama@shinshu-u.ac.jp.ORCID http://orcid.org/0000-0003-4360-6865

Funding

Japan Society for the Promotion of Science 16K10149Japan Society for the Promotion of Science 20K08667
6 · The paper itself

Abstract

backgroundWhile molecularly targeted therapies and immune checkpoint inhibitors have improved the prognosis of advanced melanoma, biomarkers are required to monitor drug responses. Circulating tumor cells (CTCs) are released from primary and/or metastatic tumors into the peripheral blood. We examined whether CTCs have potential as biomarkers by checking the number of CTCs, as well as the BRAF genotype of individual CTCs, in melanoma patients undergoing BRAF/MEK inhibitor treatment.

methodsCTCs were isolated from peripheral blood using a high-density dielectrophoretic microwell array, followed by labeling with melanoma-specific markers (MART-1 and/or gp100) and a leukocyte marker (CD45). The numbers of CTCs were analyzed in fifteen patients with stage 0-III melanoma. Furthermore, changes in CTC numbers were assessed in five patients with stage IV melanoma at four time points during BRAF/MEK inhibitor treatment, and the BRAF genotype was analyzed in CTCs isolated from one patient.

resultsWe examined CTCs in patients with stage 0-III (five samples per stage: stage 0-I, stage II, and stage III), and detected CTCs even in patients with early disease (stage 0 and I). Interestingly, recurrence occurred in the lymph nodes of one stage I patient 2 years after the detection of a high number of CTCs in the patient's blood. The total number of CTCs in four of five patients with stage IV melanoma fluctuated in response to BRAF/MEK inhibitor treatment, suggesting that CTC number has potential for use as a drug response marker in advanced disease patients. Interestingly, one of those patients had CTCs harboring seven different BRAF genotypes, and the mutated CTCs disappeared upon BRAF/MEK inhibitor treatment, except for those harboring BRAF

conclusionsCTCs are present even in the early stage of melanoma, and the number of CTCs seems to reflect patients' responses to BRAF/MEK inhibitor treatment. Furthermore, genetic heterogeneity of BRAF may contribute to resistance to BRAF/MEK inhibitors. Our findings demonstrate the usefulness of CTC analysis for monitoring responses to targeted therapies in melanoma patients, and for understanding the mechanism of drug resistance.

Indexed as

Neoplastic Cells, CirculatingAgedAged, 80 and overChemotherapy, AdjuvantDrug Resistance, NeoplasmFeasibility StudiesFemaleGenetic HeterogeneityHumansMaleMelanomaMiddle AgedMolecular Targeted TherapyNeoplasm StagingProtein Kinase InhibitorsProto-Oncogene Proteins B-rafBRAF protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins B-rafBRAFBRAF/MEK inhibitorCirculating tumor cellHeterogenous mutationMelanoma

Identifiers

PMID33731038
PMCPMC7968258

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.