外科理论与实践 ›› 2023, Vol. 28 ›› Issue (01): 7-16.doi: 10.16139/j.1007-9610.2023.01.02
收稿日期:
2023-01-16
出版日期:
2023-01-25
发布日期:
2023-03-25
通讯作者:
余俊贤,刘炳亚
E-mail:liubingya@sjtu.edu.cn
LI Jianfang, YU Junxian, YAN Chao, ZHU Zhenggang, LIU Bingya()
Received:
2023-01-16
Online:
2023-01-25
Published:
2023-03-25
Contact:
YU Junxian,LIU Bingya
E-mail:liubingya@sjtu.edu.cn
摘要:
胃癌的发病率、死亡率均较高,而胃癌的总体疗效不满意。临床上面临的早期诊断率低、肿瘤异质性、缺乏精确分型和精准治疗方案、治疗抵抗、复发与转移等问题是胃癌总体疗效不高的关键所在。为根本解决上述临床问题,需加强胃癌的基础研究,包括肿瘤基因组学、基因编辑、肿瘤微环境、炎症和衰老与肿瘤的关系、细胞分化障碍、细胞自噬与死亡、代谢紊乱、免疫治疗和药物开发等核心命题。本文将概述临床上胃癌治疗所面临的问题,并阐述针对这些临床问题的基础研究重点领域,为胃癌基础及转化研究提供思路。
中图分类号:
李建芳, 余俊贤, 严超, 朱正纲, 刘炳亚. 胃癌基础与转化研究的热点问题[J]. 外科理论与实践, 2023, 28(01): 7-16.
LI Jianfang, YU Junxian, YAN Chao, ZHU Zhenggang, LIU Bingya. Hotspots in basic and translational research of gastric cancer[J]. Journal of Surgery Concepts & Practice, 2023, 28(01): 7-16.
[1] |
EISENSTEIN M. Reading cancer's blueprint[J]. Nat Biotechnol, 2012, 30(7):581-584.
doi: 10.1038/nbt.2292 pmid: 22781673 |
[2] |
GILBERTSON R J. Mapping cancer origins[J]. Cell, 2011, 145(1):25-29.
doi: 10.1016/j.cell.2011.03.019 pmid: 21458665 |
[3] |
ZENG D, LI M, ZHOU R, et al. Tumor microenvironment characterization in gastric cancer identifies prognostic and immunotherapeutically relevant gene signatures[J]. Cancer Immunol Res, 2019, 7(5):737-750.
doi: 10.1158/2326-6066.CIR-18-0436 pmid: 30842092 |
[4] |
CHIA N Y, TAN P. Molecular classification of gastric cancer[J]. Ann Oncol, 2016, 27(5):763-769.
doi: 10.1093/annonc/mdw040 pmid: 26861606 |
[5] |
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma[J]. Nature, 2014, 513(7517):202-209.
doi: 10.1038/nature13480 |
[6] |
CRISTESCU R, LEE J, NEBOZHYN M, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes[J]. Nat Med, 2015, 21(5):449-456.
doi: 10.1038/nm.3850 pmid: 25894828 |
[7] |
PLANA D, PALMER A C, SORGER P K. Independent drug action in combination therapy: implications for precision oncology[J]. Cancer Discov, 2022, 12(3):606-624.
doi: 10.1158/2159-8290.CD-21-0212 URL |
[8] | JIN H, WANG L, BERNARDS R. Rational combinations of targeted cancer therapies: background, advances and challenges[J]. Nat Rev Drug Discov, 2022. Online ahead of print. |
[9] |
HANAHAN D, WEINBERG R A. The hallmarks of cancer[J]. Cell, 2000, 100(1):57-70.
doi: 10.1016/s0092-8674(00)81683-9 pmid: 10647931 |
[10] |
HANAHAN D, WEINBERG R A. Hallmarks of cancer: the next generation[J]. Cell, 2011, 144(5):646-674.
doi: 10.1016/j.cell.2011.02.013 pmid: 21376230 |
[11] |
HANAHAN D. Hallmarks of cancer: new dimensions[J]. Cancer Discov, 2022, 12(1):31-46.
doi: 10.1158/2159-8290.CD-21-1059 pmid: 35022204 |
[12] |
HUANG K K, RAMNARAYANAN K, ZHU F, et al. Genomic and epigenomic profiling of high-risk intestinal metaplasia reveals molecular determinants of progression to gastric cancer[J]. Cancer Cell, 2018, 33(1):137-150.
doi: S1535-6108(17)30521-4 pmid: 29290541 |
[13] |
YEOH K G, TAN P. Mapping the genomic diaspora of gastric cancer[J]. Nat Rev Cancer, 2022, 22(2):71-84.
doi: 10.1038/s41568-021-00412-7 |
[14] |
CHEN K, YANG D, LI X, et al. Mutational landscape of gastric adenocarcinoma in Chinese: implications for prognosis and therapy[J]. Proc Natl Acad Sci U S A, 2015, 112(4):1107-1112.
doi: 10.1073/pnas.1422640112 URL |
[15] |
WANG K, YUEN S T, XU J, et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer[J]. Nat Genet, 2014, 46(6):573-582.
doi: 10.1038/ng.2983 pmid: 24816253 |
[16] |
MANGHWAR H, LINDSEY K, ZHANG X, et al. CRISPR/Cas system: recent advances and future prospects for genome editing[J]. Trends Plant Sci, 2019, 24(12):1102-1125.
doi: S1360-1385(19)30243-2 pmid: 31727474 |
[17] |
ROSENBLUM D, GUTKIN A, KEDMI R, et al. CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy[J]. Sci Adv, 2020, 6(47):eabc9450.
doi: 10.1126/sciadv.abc9450 URL |
[18] | FOY S P, JACOBY K, BOTA D A, et al. Non-viral precision T cell receptor replacement for personalized cell therapy[J]. Nature, 2022:1-10. |
[19] |
SAHA K, SONTHEIMER E J, BROOKS P J, et al. The NIH somatic cell genome editing program[J]. Nature, 2021, 592(7853):195-204.
doi: 10.1038/s41586-021-03191-1 |
[20] | GRADY W M, YU M, MARKOWITZ S D. Epigenetic alterations in the gastrointestinal tract: current and emerging use for biomarkers of cancer[J]. Gastroentero-logy, 2021, 160(3):690-709. |
[21] |
HUANG T, SONG C, ZHENG L, et al. The roles of extracellular vesicles in gastric cancer development, microenvironment, anti-cancer drug resistance, and therapy[J]. Mol Cancer, 2019, 18(1):62.
doi: 10.1186/s12943-019-0967-5 pmid: 30925929 |
[22] |
EISENSTEIN M. Seven technologies to watch in 2022[J]. Nature, 2022, 601(7894):658-661.
doi: 10.1038/d41586-022-00163-x |
[23] |
KUMAR V, RAMNARAYANAN K, SUNDAR R, et al. Single-cell atlas of lineage states, tumor microenvironment, and subtype-specific expression programs in gastric cancer[J]. Cancer Discov, 2022, 12(3):670-691.
doi: 10.1158/2159-8290.CD-21-0683 URL |
[24] |
COUSSENS L M, WERB Z. Inflammation and cancer[J]. Nature, 2002, 420(6917):860-867.
doi: 10.1038/nature01322 |
[25] |
DIAKOS C I, CHARLES K A, MCMILLAN D C, et al. Cancer-related inflammation and treatment effectiveness[J]. Lancet Oncol, 2014, 15(11):e493-e503.
doi: 10.1016/S1470-2045(14)70263-3 URL |
[26] |
SCHMITT C A, WANG B, DEMARIA M. Senescence and cancer-role and therapeutic opportunities[J]. Nat Rev Clin Oncol, 2022, 19(10):619-636.
doi: 10.1038/s41571-022-00668-4 |
[27] | BLAGOSKLONNY M V. Hallmarks of cancer and hallmarks of aging[J]. Aging (Albany NY), 2022, 14(9):4176-4187. |
[28] |
PRASETYANTI P R, MEDEMA J P. Intra-tumor heterogeneity from a cancer stem cell perspective[J]. Mol Cancer, 2017, 16(1):41.
doi: 10.1186/s12943-017-0600-4 pmid: 28209166 |
[29] |
FATEHULLAH A, TERAKADO Y, SAGIRAJU S, et al. A tumour-resident Lgr5(+) stem-cell-like pool drives the establishment and progression of advanced gastric cancers[J]. Nat Cell Biol, 2021, 23(12):1299-1313.
doi: 10.1038/s41556-021-00793-9 |
[30] | WILLET S G, LEWIS M A, MIAO Z F, et al. Regenerative proliferation of differentiated cells by mTORC1-dependent paligenosis[J]. EMBO J, 2018, 37(7):e98311. |
[31] |
MIAO Z F, LEWIS M A, CHO C J, et al. A dedicated evolutionarily conserved molecular network licenses differentiated cells to return to the cell cycle[J]. Dev Cell, 2020, 55(2):178-194.
doi: 10.1016/j.devcel.2020.07.005 URL |
[32] |
WHITE E, MEHNERT J M, CHAN C S. Autophagy, metabolism, and cancer[J]. Clin Cancer Res, 2015, 21(22):5037-5046.
doi: 10.1158/1078-0432.CCR-15-0490 pmid: 26567363 |
[33] |
LI X, HE S, MA B. Autophagy and autophagy-related proteins in cancer[J]. Mol Cancer, 2020, 19(1):12.
doi: 10.1186/s12943-020-1138-4 pmid: 31969156 |
[34] |
WU Q, MA J, WEI J, et al. lncRNA SNHG11 promotes gastric cancer progression by activating the Wnt/beta-catenin pathway and oncogenic autophagy[J]. Mol Ther, 2021, 29(3):1258-1278.
doi: 10.1016/j.ymthe.2020.10.011 URL |
[35] |
STRASSER A, VAUX D L. Cell death in the origin and treatment of cancer[J]. Mol Cell, 2020, 78(6):1045-1054.
doi: S1097-2765(20)30315-4 pmid: 32516599 |
[36] |
MOU Y, WANG J, WU J, et al. Ferroptosis, a new form of cell death: opportunities and challenges in cancer[J]. J Hematol Oncol, 2019, 12(1):34.
doi: 10.1186/s13045-019-0720-y |
[37] |
JIANG X, STOCKWELL B R, CONRAD M. Ferroptosis: mechanisms, biology and role in disease[J]. Nat Rev Mol Cell Biol, 2021, 22(4):266-282.
doi: 10.1038/s41580-020-00324-8 |
[38] |
WANG Y, ZHENG L, SHANG W, et al. Wnt/beta-catenin signaling confers ferroptosis resistance by targeting GPX4 in gastric cancer[J]. Cell Death Differ, 2022, 29(11):2190-2202.
doi: 10.1038/s41418-022-01008-w pmid: 35534546 |
[39] |
O'NEIL N J, BAILEY M L, HIETER P. Synthetic letha-lity and cancer[J]. Nat Rev Genet, 2017, 18(10):613-623.
doi: 10.1038/nrg.2017.47 URL |
[40] |
SETTON J, ZINDA M, RIAZ N, et al. Synthetic lethality in cancer therapeutics: the next generation[J]. Cancer Discov, 2021, 11(7):1626-1635.
doi: 10.1158/2159-8290.CD-20-1503 pmid: 33795234 |
[41] |
AN L, CAO Z, NIE P, et al. Combinatorial targeting of Hippo-STRIPAK and PARP elicits synthetic lethality in gastrointestinal cancers[J]. J Clin Invest, 2022, 132(9):e155468.
doi: 10.1172/JCI155468 URL |
[42] |
SLETTENAAR V I, WILSON J L. The chemokine network: a target in cancer biology?[J]. Adv Drug Deliv Rev, 2006, 58(8):962-974.
doi: 10.1016/j.addr.2006.03.012 URL |
[43] |
YANG D, ZHANG W, ZHANG H, et al. Progress, opportunity, and perspective on exosome isolation-efforts for efficient exosome-based theranostics[J]. Theranostics, 2020, 10(8):3684-3707.
doi: 10.7150/thno.41580 URL |
[44] |
MATHEWS J C, NADEEM S, POURYAHYA M, et al. Functional network analysis reveals an immune tolerance mechanism in cancer[J]. Proc Natl Acad Sci U S A, 2020, 117(28):16339-16345.
doi: 10.1073/pnas.2002179117 URL |
[45] |
SHEN D D, PANG J R, BI Y P, et al. LSD1 deletion decreases exosomal PD-L1 and restores T-cell response in gastric cancer[J]. Mol Cancer, 2022, 21(1):75.
doi: 10.1186/s12943-022-01557-1 |
[46] |
GDOVIN M J, KADRI N, RIOS L, et al. Focal photodynamic intracellular acidification as a cancer therapeutic[J]. Semin Cancer Biol, 2017, 43:147-156.
doi: S1044-579X(17)30023-8 pmid: 28215969 |
[47] |
PAVLOVA N N, ZHU J, THOMPSON C B. The hallmarks of cancer metabolism: still emerging[J]. Cell Metab, 2022, 34(3):355-377.
doi: 10.1016/j.cmet.2022.01.007 URL |
[48] | LU Y X, JU H Q, LIU Z X, et al. ME1 regulates NADPH homeostasis to promote gastric cancer growth and metastasis[J]. Cancer Res, 2018, 78(8):1972-1985. |
[49] |
THOMAS A, TEICHER B A, HASSAN R. Antibody-drug conjugates for cancer therapy[J]. Lancet Oncol, 2016, 17(6):e254-e262.
doi: 10.1016/S1470-2045(16)30030-4 pmid: 27299281 |
[50] |
CHEN W, YUAN Y, JIANG X. Antibody and antibody fragments for cancer immunotherapy[J]. J Control Release, 2020, 328:395-406.
doi: 10.1016/j.jconrel.2020.08.021 URL |
[51] | FU Z, LI S, HAN S, et al. Antibody drug conjugate: the "biological missile" for targeted cancer therapy[J]. Signal Transduct Target Ther, 2022, 7(1):93. |
[52] |
OGITANI Y, AIDA T, HAGIHARA K, et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoiso-merase Ⅰ inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1[J]. Clin Cancer Res, 2016, 22(20):5097-5108.
doi: 10.1158/1078-0432.CCR-15-2822 URL |
[53] |
XIONG W, GAO Y, WEI W, et al. Extracellular and nuclear PD-L1 in modulating cancer immunotherapy[J]. Trends Cancer, 2021, 7(9):837-846.
doi: 10.1016/j.trecan.2021.03.003 pmid: 33903073 |
[54] | DEPIL S, DUCHATEAU P, GRUPP S A, et al. ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges[J]. Nat Rev Drug Discov, 2020, 19(3):185-199. |
[55] |
NEWICK K, O'BRIEN S, MOON E, et al. CAR T cell therapy for solid tumors[J]. Annu Rev Med, 2017, 68:139-152.
doi: 10.1146/annurev-med-062315-120245 pmid: 27860544 |
[56] |
SELLARS M C, WU C J, FRITSCH E F. Cancer vaccines: building a bridge over troubled waters[J]. Cell, 2022, 185(15):2770-2788.
doi: 10.1016/j.cell.2022.06.035 pmid: 35835100 |
[57] |
BASELGA J, ARRIBAS J. Treating cancer’s kinase ‘addiction’[J]. Nat Med, 2004, 10(8):786-787.
doi: 10.1038/nm0804-786 |
[58] |
PATWARDHAN A, CHENG N, TREJO J. Post-translational modifications of G protein-coupled receptors control cellular signaling dynamics in space and time[J]. Pharmacol Rev, 2021, 73(1):120-151.
doi: 10.1124/pharmrev.120.000082 pmid: 33268549 |
[59] |
CZUBA L C, HILLGREN K M, SWAAN P W. Post-translational modifications of transporters[J]. Pharmacol Ther, 2018, 192:88-99.
doi: 10.1016/j.pharmthera.2018.06.013 URL |
[60] | BÉKÉS M, LANGLEY D R, CREWS C M. PROTAC targeted protein degraders: the past is prologue[J]. Nat Rev Drug Discov, 2022, 21(3):181-200. |
[61] |
SALAMI J, CREWS C M. Waste disposal-an attractive strategy for cancer therapy[J]. Science, 2017, 355(6330):1163-1167.
doi: 10.1126/science.aam7340 pmid: 28302825 |
[62] |
KWONG L N, HEFFERNAN T P, CHIN L. A systems biology approach to personalizing therapeutic combinations[J]. Cancer Discov, 2013, 3(12):1339-1344.
doi: 10.1158/2159-8290.CD-13-0394 pmid: 24327696 |
[63] |
GLASER P, BOONE C. Beyond the genome: from geno-mics to systems biology[J]. Curr Opin Microbiol, 2004, 7(5):489-491.
doi: 10.1016/j.mib.2004.08.016 URL |
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