「乳がん」カテゴリーアーカイブ

がんマーカー　早期診断、確定診断、病勢、予後予測に役立つバイオマーカーに関する論文のまとめ

がんは早期に発見すれば治療が容易で完治することが多いため、がん撲滅のためには早期診断が可能なバイオマーカーの開発が期待されています。また、がんの薬剤への応答性は個人によって大きく異なるため、テイラーメード医療の必要性も広く認識されています。このような事情から、がんの早期診断、確定診断、病勢、予後予測、テイラーメード医療に役立つバイオマーカーの開発に、世界中の研究者がしのぎを削っています。こうした新規バイオマーカー（候補）に関する論文は膨大な数に上り、把握するのがなかなか大変です。

臨床の現場で実用的かどうかは、患者に負担をかけない侵襲性の低い（尿、唾液、血液など）検体が使えるかどうか、コストがかからないか、迅速か、誰がやっても同じ結果が容易に得られるかなどが重要になってきます。

がんのバイオマーカーであるということは、発がんやがんの成長、転移などのメカニズムに直接関与する可能性があるので、新規がんバイオマーカーを見つけるということは、とりもなおさずがんのメカニズムに迫る可能性が強まることにもなり、その意義は大きなものがあります。

 

がんマーカー

AFP (Liver Cancer), BCR-ABL (Chronic Myeloid Leukemia), BRCA1 / BRCA2 (Breast/Ovarian Cancer), BRAF V600E (Melanoma/Colorectal Cancer), CA-125 (Ovarian Cancer), CA19.9 (Pancreatic Cancer), CEA (Colorectal Cancer), EGFR (Non-small-cell lung carcinoma), HER-2 (Breast Cancer), KIT (Gastrointestinal stromal tumor), PSA (Prostate Specific Antigen) (Prostate Cancer), S100 (Melanoma)　（Cancer biomarker　Wikipedia）

  1. Goossens et al., Cancer biomarker discovery and validation. Transl Cancer Res. 2015 Jun; 4(3): 256–269. there has been a large gap between multiple initial reports of biomarkers, often with diagnostic performance that cannot be reproduced in later studies
  2. Henry and Hayes. Cancer biomarkers Molecular Oncology 06 February 2012
  3. Cancer Biomarker Discovery SinoBiological
  4. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Clinical Practice http://sites.utoronto.ca/acdclab/pubs/PM/18695711.pdf  The introduction of technologies such as mass spectrometry and protein and DNA arrays, combined with our understanding of the human genome, has enabled simultaneous examination of thousands of proteins and genes in single experiments, which has led to renewed interest in discovering novel biomarkers for cancer.中略 Cancer biomarkers can be DNA, mRNA, proteins, metabolites, or processes such as apoptosis, angiogenesis or proliferation.

 

がんマーカーとしての変異遺伝子

発がんは多くの場合、遺伝子の変異の蓄積を伴います。

K-Ras変異とがん

epidermal growth factor receptorの変異とがん

c-Kitの変異とがん

Braf の変異とがん

  1. Andre et al.,  Biomarker Discovery, Development, and Implementation in France: A Report from the French National Cancer Institute and Cooperative Groups. March 2012 Clinical Cancer Research March 2012 Volume 18, Issue 6

 

がんマーカーとしての細胞外小胞の利用

Kosaka et al., Exploiting the message from cancer: the diagnostic value of extracellular vesicles for clinical applications.　Experimental & Molecular Medicine 15 March 2019; volume 51, pages1–9. https://www.nature.com/articles/s12276-019-0219-1 細胞外小胞の種類を説明した図がわかりやすい

 

乳がん

  1. Comment on ‘BAG-1 as a biomarker in early breast cancer prognosis: a systematic review with meta-analyses’ 15 March 2018 British Journal of Cancer volume 118, pages　1152–1153
  2. Circulating Microparticles in Breast Cancer Patients: A Comparative Analysis with Established Biomarkers. ANTICANCER RESEARCH 28: 1107-1112 (2008)

TNBC

  1. Sukumar et al.,  Triple-negative breast cancer: promising prognostic biomarkers currently in development. Expert Review of Anticancer Therapy 24 Feb 2021
  2. Biomarkers in Triple-Negative Breast Cancer: State-of-the-Art and Future Perspectives. Int J Mol Sci. 2020 Jul; 21(13): 4579. MDPIジャーナルに掲載されたレビュー論文　Lehmann et al. proposed a division of TNBCs into seven molecular subtypes: immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), luminal androgen receptor (LAR), unstable (UNS) subtype, and two basal-like subtypes (BL1 and BL2) [3]. Then, a subclassification refinement was performed, to define only four groups BL1 (immune-activated), BL2 (immune-suppressed), M (including most of the MSL), and LAR [4]. These classifications can, in theory, be used as prognostic and predictive tool for better patient selection and personalized treatments. 中略 However, sound clinical applications of this molecular classification are yet to appear [8].　個別化医療のためのTNBC
    のタイプ分けの努力とその限界
  3. Bao et al.　Exploring specific prognostic biomarkers in triple-negative breast cancer.  Fan Cell Death & Disease 24 October 2019; volume 10, Article number: 807
  4. Potential clinically useful prognostic biomarkers in triple-negative breast cancer: preliminary results of a retrospective analysis. Breast Cancer (Dove Med Press). 2018 Nov 23; 10: 177–194.
  5. Lafont et al., CD73: a new biomarker in triple-negative breast cancer. Translational Cancer Research Vol 7, Supplement 5 (June 2018)

 

大腸がんのマーカー蛋白質

Zheng et al., A circulating extracellular vesicles-based novel screening tool for colorectal cancer revealed by shotgun and data-independent acquisition mass spectrometry.　Journal of Extracellular Vesicles 14 April 2020; Volume 9, Issue 1

Zhong et al. Serum extracellular vesicles contain SPARC and LRG1 as biomarkers of colon cancer and differ by tumour primary location. EBioMedicine 2019 Nov 18; 50:211-223.

Lee et al. Discovery of a diagnostic biomarker for colon cancer through proteomic profiling of small extracellular vesicles. BMC Cancer. 2018 Nov 1; 18: 1058.

Quantitative mass spectrometry analysis reveals a panel of nine proteins as diagnostic markers for colon adenocarcinomas. Oncotarget. 2018 Mar 2; 9(17): 13530–13544.

Shiromizu et al., Quantitation of putative colorectal cancer biomarker candidates in serum extracellular vesicles by targeted proteomics.　Scientific Reports 06 October 2017 ; volume 7, Article number: 12782.　 annexins A3, A4, and A11

  1. 英語表記の日本語訳における注意点 colorectal cancer「結腸直腸癌」ではなく、「大腸癌」と訳すべきである。日本の大腸癌診療において「結腸直腸癌」という語は一般的に用いられていない
  2. 大腸がん(結腸がん・直腸がん)　ColoRectal Cancer：CRC まつおか内視鏡内科　富山県富山市　大腸がんの発生には大腸腺腫(ポリープ)が徐々に大きくなりがん化するものと、正常粘膜から突然がん化するものの2種類あります。多くは前者

大腸がん予後予測バイオマーカー

バイマーカーという言葉は非常に広い意味で使われており、単なる遺伝子発現だけでなく、画像診断であったりもします。

  1. AIによる大腸がん転帰の予測マーカーを開発／Lancet　ケアネット2020/02/17　ノルウェー・オスロ大学病院のOle-Johan Skrede氏らは、ディープラーニング（深層学習）を用いて、従来の病理組織画像から大腸がんの転帰を予測するバイオマーカー（DoMore-v1-CRC）を開発し、その臨床的有用性を確認した。
  2. The Lymphocyte-to-Monocyte Ratio is a Superior Predictor of Overall Survival in Comparison to Established Biomarkers of Resectable Colorectal Cancer. Ann Surg. 2017 Mar; 265(3): 539–546.

 

トリプルネガティブタイプの乳がん（Triple Negative Breast Cancer; TNBC）について

トリプルネガティブ乳がん（TNBC)に関する解説

  1. Triple-Negative Breast Cancer cdc.gov
  2. A New Way to Fight Triple-Negative Breast Cancer Arrives March 3, 2021 Kristie L. Kahl　  curetoday.com
  3. Treating Triple-Negative Breast Cancer: Recent Progress and What’s to Come Several sessions at SABCS highlighted our gains against this aggressive form of breast cancer—and the challenges that still remain By BCRF | January 20, 2021 BCRF. Ninety-five percent of newly diagnosed TNBC patients have early-stage disease, and based on recent clinical trial results, their five-year disease-free survival is well over 80 percent.
  4. Update on Strategies to Improve Treatment for Triple Negative Breast Cancer Keytruda, Tecentriq, and Sacituzumab Govitecan (IMMU-132) are promising TNBC treatment advances. CANCERCONNECTDEC 11, 2020
  5. Treatment of Triple-negative Breast Cancer (cancer.org) chemotherapy (chemo) is the main systemic treatment option. And although TNBC tends to respond well to initial chemo, it tends to come back (recur) more frequently than other breast cancers.
  6. Triple-Negative Breast Cancer breastcancer.org

 

トリプルネガティブ乳がん（TNBC)の臨床試験IMpassion031

IMpassion031 is a phase III trial in patients with early-stage TNBC testing the safety and effectiveness of the checkpoint inhibitor atezolizumab used in tandem with standard chemotherapy prior to surgery (called neoadjuvant therapy). ‥　IMpassion031 involved 333 newly diagnosed patients with TNBC who were randomly assigned to receive either atezolizumab plus chemotherapy (nab-paclitaxel, doxorubicin, or cyclophosphamide) or the same chemotherapy agents plus a placebo prior to undergoing breast cancer surgery.

https://www.bcrf.org/sabcs-2020-triple-negative-breast-cancer-tnbc-clinical-trial-updates

  1. Trial finds benefit of immunotherapy-chemotherapy combination in early-stage triple-negative breast cancer

 

トリプルネガティブ乳がん（TNBC)の臨床試験

  1. Effect of Adjuvant Paclitaxel and Carboplatin on Survival in Women With Triple-Negative Breast Cancer A Phase 3 Randomized Clinical Trial Ke-Da Yu, MD, PhD1; Fu-Gui Ye, MD1; Min He, MD1; et al　JAMA Oncol. 2020;6(9):1390-1396. doi:10.1001/jamaoncol.2020.2965　August 13, 2020

 

トリプルネガティブ乳がん（TNBC)に対する免疫療法

  1. Immunotherapy in Triple-Negative Breast Cancer: How to Move Forward October 1, 2020 Carlos H. dos Anjos, MD, and Romualdo Barroso-Sousa, MD, PhD　ASCO Daily News. Immune checkpoint blockade (ICB) has revolutionized the treatment of early and advanced solid tumors, including triple-negative breast cancer (TNBC), especially when combined with cytotoxic chemotherapy. Only a fraction of patients with TNBC benefit from ICB plus cytotoxic chemotherapy, so biomarkers to predict a response are urgently needed, with emphasis on composite biomarkers.

 

トリプルネガティブ乳がん（TNBC)に関する症例報告

  1. Multidisciplinary considerations in the treatment of triple‐negative breast cancer.  Jennifer R. Bellon MD Harold J. Burstein MD, PhD Elizabeth S. Frank EdM Elizabeth A. Mittendorf MD, PhD Tari A. King MD First published: 28 September 2020 https://doi.org/10.3322/caac.21643 A Cancer Journal of Clinicians

 

トリプルネガティブ乳がん（TNBC)に関する論文

  1. A Strategy to Fight against Triple-Negative Breast Cancer: pH-Responsive Hexahistidine-Metal Assemblies with High-Payload Drugs Long Zhang, Hongyan Xu, Xiaoxiao Wu, Wenjuan Huang, Tinghong Zhang, Pengyan Hao, Bo Peng*, and Xingjie Zan* Cite this: ACS Appl. Bio Mater. 2020, 3, 8, 5331–5341 Publication Date:July 7, 2020 https://doi.org/10.1021/acsabm.0c00653　TNBC has the highest rate of metastatic disease and the poorest overall five-year survival rate (less than 25% for TNBC) compared to other breast cancer subtypes (90.3 and 92.5% for ER+PR+/HER2+ and ER+PR+/HER2, respectively).

 

トリプルネガティブ乳がん（TNBC)に関するレビュー論文

  1. Most neoadjuvant chemotherapy for triple-negative breast cancer should include platinum. Rebecca Dent Hope S Rugo Published:January, 2021DOI:https://doi.org/10.1016/S1470-2045(20)30747-6 THE LANCET Oncology　PERSPECTIVES|SPOTLIGHT| VOLUME 22, ISSUE 1, P27-28, JANUARY 01, 2021
  2. Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies. Antonio Marra, Dario Trapani, Giulia Viale, Carmen Criscitiello & Giuseppe Curigliano npj Breast Cancer volume 6, Article number: 54 (2020) Published: 16 October 2020
  3. Emerging CAR-T Cell Therapy for the Treatment of Triple-Negative Breast Cancer Sundee Dees, Rajkumar Ganesan, Sanjaya Singh and Iqbal S. Grewal DOI: 10.1158/1535-7163.MCT-20-0385 Published December 2020 Molecular Cancer Therapeutics
  4. A Review of Natural Therapies Potentially Relevant in Triple Negative Breast Cancer Aimed at Targeting Cancer Cell Vulnerabilitie. Myfanwy Jane Webb, BScHons, PhD, Craig Kukard, MBChB, MMed, FRACP Craig Kukard University of Newcastle, Newcastle, NSW, Australia See all articles by this author Search Google Scholar for this author First Published November 27, 2020 Review Article https://doi.org/10.1177/1534735420975861
  5. Triple-negative breast cancer molecular subtyping and treatment progress. Li Yin, Jiang-Jie Duan, Xiu-Wu Bian & Shi-cang Yu Breast Cancer Research volume 22, Article number: 61 (2020) Published: 09 June 2020

 

トリプルネガティブ乳がん体験談

  1. Triple-Negative Breast: Cancer Pat Prijatel, diagnosed with early-stage triple-negative breast cancer in May 2006 and author of Surviving Triple Negative Breast Cancer, discusses what that diagnosis has meant to her; why she started her blog, Positives About Negative; and advice she would give a person newly diagnosed.（インタビュー音声22：58 breastcancer.org）