Synthetic lethality on drug discovery: an update on cancer therapy

被引:15
|
作者
Yar, M. Shahar [1 ]
Haider, Kashif [1 ]
Gohel, Vivek [2 ]
Siddiqui, Nasir Ali [3 ]
Kamal, Ahmed [1 ]
机构
[1] Jamia Hamdard, Sch Pharmaceut Educ & Res, Dept Pharmaceut Chem, New Delhi 110062, India
[2] NIPER SAS Nagar, Dept Pharmacol & Toxicol, Mohali, India
[3] King Saud Univ, Coll Pharm, Riyadh, Saudi Arabia
关键词
Synthetic lethality; PARP; BRCA; cancer; METASTATIC COLORECTAL-CANCER; DEPENDENT PROTEIN-KINASE; HOMOLOGY-DIRECTED REPAIR; DNA-DAMAGE RESPONSE; BRCA MUTANT-CELLS; POLY(ADP-RIBOSE) POLYMERASE; PARP INHIBITOR; STRAND BREAKS; MYC; ACTIVATION;
D O I
10.1080/17460441.2020.1744560
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: A novel anticancer therapy is the need of the hour due to growing incidences of resistance to first line cancer chemotherapy. Synthetic lethality (SL) is one of the new age treatment methods being explored for combating the resistance to anticancer agents. In this method, cell mutations are exploited for the development of new therapeutic agents, where, if there is loss of function of one gene, the cell mutations can still be fixed by alternative machinery but if two genes involved in DNA repair undergo loss of function, it causes lethality to the cell. Areas covered: The authors condense findings of SL-based novel anticancer regimen. The review emphasizes some of the SL based clinical and preclinical studies of novel targets and therapy. Expert opinion: SL conceptualizes a resolution against treatment resistance to anticancer regimen by recognition of therapeutic vulnerabilities in particular cancer cells. A multitude of clinical trials associated with SL and DNA repair are being conducted that will be useful in obtaining a clearer picture pertaining to the use of cancer biomarkers and effectiveness of drugs acting via target-based molecular changes. Furthermore, new anticancer regimen focused on personalized medicines will emerge basing their development upon SL.
引用
收藏
页码:823 / 832
页数:10
相关论文
共 50 条
  • [21] The role of drug-metabolizing enzymes in synthetic lethality of cancer
    Zeng, Zekun
    Zheng, Wenfang
    Hou, Peng
    [J]. PHARMACOLOGY & THERAPEUTICS, 2022, 240
  • [22] Synthetic lethality and cancer
    O'Neil, Nigel J.
    Bailey, Melanie L.
    Hieter, Philip
    [J]. NATURE REVIEWS GENETICS, 2017, 18 (10) : 613 - 623
  • [23] Synthetic lethality guiding selection of drug combinations in ovarian cancer
    Heinzel, Andreas
    Marhold, Maximilian
    Mayer, Paul
    Schwarz, Michael
    Tomasich, Erwin
    Lukas, Arno
    Krainer, Michael
    Perco, Paul
    [J]. PLOS ONE, 2019, 14 (01):
  • [24] Synthetic lethality and cancer
    Nigel J. O'Neil
    Melanie L. Bailey
    Philip Hieter
    [J]. Nature Reviews Genetics, 2017, 18 : 613 - 623
  • [25] Drug-drug synthetic lethality to combat cancer: From bench to bedside
    Chen, Yu
    Yang, Wu
    Zheng, Jiaojiao
    Bernards, Rene
    Jin, Haojie
    [J]. CLINICAL AND TRANSLATIONAL MEDICINE, 2023, 13 (05):
  • [26] SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets
    Guo, Jing
    Liu, Hui
    Zheng, Jie
    [J]. NUCLEIC ACIDS RESEARCH, 2016, 44 (D1) : D1011 - D1017
  • [27] The Implication of Topoisomerase II Inhibitors in Synthetic Lethality for Cancer Therapy
    Matias-Barrios, Victor M. M.
    Dong, Xuesen
    [J]. PHARMACEUTICALS, 2023, 16 (01)
  • [28] Rapid Inhibitor Discovery by Exploiting Synthetic Lethality
    Muscato, Jacob D.
    Morris, Heidi G.
    Mychack, Aaron
    Rajagopal, Mithila
    Baidin, Vadim
    Hesser, Anthony R.
    Lee, Wonsik
    Inecik, Kemal
    Wilson, Laura J.
    Kraml, Christina M.
    Meredith, Timothy C.
    Walker, Suzanne
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2022, 144 (08) : 3696 - 3705
  • [29] Synthetic Lethality -- A New Direction in Cancer-Drug Development.
    Iglehart, J. Dirk
    Silver, Daniel P.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (02): : 189 - 191
  • [30] Drug combinations for breast cancer based on synthetic lethality screens in yeast
    Schwarz, Michael
    Tomasich, Erwin
    Marhold, Maximilian
    Heinzel, Andreas
    Perco, Paul
    Horak, Peter
    Mayer, Bernd
    Krainer, Michael
    [J]. CANCER RESEARCH, 2016, 76