Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Molecular Cancer
Published in: Molecular Cancer 1/2016

Open Access 01-12-2016 | Review

Synthetic lethality in lung cancer and translation to clinical therapies

Authors: Ada W. Y. Leung, Tanya de Silva, Marcel B. Bally, William W. Lockwood

Published in: Molecular Cancer | Issue 1/2016

Login to get access

Abstract

Lung cancer is a heterogeneous disease consisting of multiple histological subtypes each driven by unique genetic alterations. Despite the development of targeted therapies that inhibit the oncogenic mutations driving a subset of lung cancer cases, there is a paucity of effective treatments for the majority of lung cancer patients and new strategies are urgently needed. In recent years, the concept of synthetic lethality has been established as an effective approach for discovering novel cancer-specific targets as well as a method to improve the efficacy of existing drugs which provide partial but insufficient benefits for patients. In this review, we discuss the concept of synthetic lethality, the various types of synthetic lethal interactions in the context of oncology and the approaches used to identify these interactions, including recent advances that have transformed the ability to discover novel synthetic lethal combinations on a global scale. Lastly, we describe the specific synthetic lethal interactions identified in lung cancer to date and explore the pharmacological challenges and considerations in translating these discoveries to the clinic.
Literature
1.
2.
Sullivan JP, Minna JD, Shay JW. Evidence for self-renewing lung cancer stem cells and their implications in tumor initiation, progression, and targeted therapy. Cancer Metastasis Rev. 2010;29:61–72.PubMedPubMedCentralCrossRef
3.
Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175–80.PubMedCrossRef
4.
Lockwood WW, Wilson IM, Coe BP, Chari R, Pikor LA, Thu KL, Solis LM, Nunez MI, Behrens C, Yee J, et al. Divergent genomic and epigenomic landscapes of lung cancer subtypes underscore the selection of different oncogenic pathways during tumor development. PLoS One. 2012;7:e37775.PubMedPubMedCentralCrossRef
5.
Hammerman PS, Lawrence MS, Voet D, Jing R, Cibulskis K, Sivachenko A, Stojanov P, McKenna A, Lander ES, Gabriel S, et al. Comprehensive genomic characterization of squamous cell lung cancers. Nature. 2012;489:519–525.CrossRef
6.
George J, Lim JS, Jang SJ, Cun Y, Ozretic L, Kong G, Leenders F, Lu X, Fernandez-Cuesta L, Bosco G, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524:47–53.PubMedPubMedCentralCrossRef
7.
Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–500.PubMedCrossRef
8.
Pao W, Miller V, Zakowski M, Doherty J, Politi K, Sarkaria I, Singh B, Heelan R, Rusch V, Fulton L, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A. 2004;101:13306–11.PubMedPubMedCentralCrossRef
9.
Mok T, Wu YL, Zhang L. A small step towards personalized medicine for non-small cell lung cancer. Discov Med. 2009;8:227–31.PubMed
10.
11.
Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat Commun. 2016;7:10501.PubMedPubMedCentralCrossRef
12.
Kaelin Jr WG. The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer. 2005;5:689–98.PubMedCrossRef
13.
14.
Brough R, Frankum JR, Costa-Cabral S, Lord CJ, Ashworth A. Searching for synthetic lethality in cancer. Curr Opin Genet Dev. 2011;21:34–41.PubMedCrossRef
15.
Lucchesi JC. Synthetic lethality and semi-lethality among functionally related mutants of Drosophila melanfgaster. Genetics. 1968;59:37–44.PubMedPubMedCentral
16.
Benedict RC. The origin of new varieties of nephrolepis by orthogenetic saltation II. Regressive variation or reversion from the primary and secondary sports of bostoniensis. Am J Bot. 1922;9:140–57.CrossRef
17.
Dobzhansky T. Genetics of natural populations. Xiii. Recombination and variability in populations of drosophila pseudoobscura. Genetics. 1946;31:269–90.PubMedPubMedCentral
18.
James SW, Silflow CD, Thompson MD, Ranum LP, Lefebvre PA. Extragenic suppression and synthetic lethality among Chlamydomonas reinhardtii mutants resistant to anti-microtubule drugs. Genetics. 1989;122:567–77.PubMedPubMedCentral
19.
Goodson HV, Anderson BL, Warrick HM, Pon LA, Spudich JA. Synthetic lethality screen identifies a novel yeast myosin I gene (MYO5): myosin I proteins are required for polarization of the actin cytoskeleton. J Cell Biol. 1996;133:1277–91.PubMedCrossRef
20.
Hartwell LH, Szankasi P, Roberts CJ, Murray AW, Friend SH. Integrating genetic approaches into the discovery of anticancer drugs. Science. 1997;278:1064–8.PubMedCrossRef
21.
Johnson CD, Rand JB, Herman RK, Stern BD, Russell RL. The acetylcholinesterase genes of C. elegans: identification of a third gene (ace-3) and mosaic mapping of a synthetic lethal phenotype. Neuron. 1988;1:165–73.PubMedCrossRef
22.
Simons A, Dafni N, Dotan I, Oron Y, Canaani D. Establishment of a chemical synthetic lethality screen in cultured human cells. Genome Res. 2001;11:266–73.PubMedPubMedCentralCrossRef
23.
Farmer H, McCabe N, Lord CJ, Tutt ANJ, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–21.PubMedCrossRef
24.
Paddison PJ, Silva JM, Conklin DS, Schlabach M, Li M, Aruleba S, Balija V, O’Shaughnessy A, Gnoj L, Scobie K, et al. A resource for large-scale RNA-interference-based screens in mammals. Nature. 2004;428:427–31.PubMedCrossRef
25.
Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, Kerkhoven RM, Madiredjo M, Nijkamp W, Weigelt B, et al. A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature. 2004;428:431–7.PubMedCrossRef
26.
Aza-Blanc P, Cooper CL, Wagner K, Batalov S, Deveraux QL, Cooke MP. Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. Mol Cell. 2003;12:627–37.PubMedCrossRef
27.
Moutsatsos IK, Parker CN. Recent advances in quantitative high throughput and high content data analysis. Expert Opin Drug Discov. 2016;11:415–423.PubMedCrossRef
28.
Park SJ, Saito-Adachi M, Komiyama Y, Nakai K. Advances, practice, and clinical perspectives in high-throughput sequencing. Oral Diseases. 2016;22:353–364.PubMedCrossRef
29.
Wang T, Wei JJ, Sabatini DM, Lander ES. Genetic screens in human cells using the CRISPR-Cas9 system. Science. 2014;343:80–4.PubMedCrossRef
30.
Xue HY, Ji LJ, Gao AM, Liu P, He JD, Lu XJ. CRISPR-Cas9 for medical genetic screens: applications and future perspectives. J Med Genet. 2016;53:91–7.PubMedCrossRef
31.
Basu B, Yap TA, Molife LR, de Bono JS. Targeting the DNA damage response in oncology: past, present and future perspectives. Curr Opin Oncol. 2012;24:316–24.PubMedCrossRef
32.
Jackson RA, Chen ES. Synthetic lethal approaches for assessing combinatorial efficacy of chemotherapeutic drugs. Pharmacol Ther. 2016;162:69–85.PubMedCrossRef
33.
Horn CR, Cochrane GM. An audit of morbidity associated with chronic asthma in general practice. Respir Med. 1989;83:71–5.PubMedCrossRef
34.
Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer. 2012;12:323–34.PubMedCrossRef
35.
36.
Olivier M, Hollstein M, Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol. 2010;2:a001008.PubMedPubMedCentralCrossRef
37.
38.
Lazo JS, Sharlow ER. Drugging undruggable molecular cancer targets. Annu Rev Pharmacol Toxicol. 2016;56:23–40.PubMedCrossRef
39.
Gurpinar E, Vousden KH. Hitting cancers’ weak spots: vulnerabilities imposed by p53 mutation. Trends Cell Biol. 2015;25:486–95.PubMedCrossRef
40.
41.
Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72:1117–30.PubMedPubMedCentralCrossRef
42.
Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–7.PubMedCrossRef
43.
44.
Mendes-Pereira AM, Martin SA, Brough R, McCarthy A, Taylor JR, Kim JS, Waldman T, Lord CJ, Ashworth A. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med. 2009;1:315–22.PubMedPubMedCentralCrossRef
45.
Riabinska A, Daheim M, Herter-Sprie GS, Winkler J, Fritz C, Hallek M, Thomas RK, Kreuzer KA, Frenzel LP, Monfared P, et al. Therapeutic targeting of a robust non-oncogene addiction to PRKDC in ATM-defective tumors. Sci Transl Med. 2013;5:189ra178.CrossRef
46.
Shackelford DB, Abt E, Gerken L, Vasquez DS, Seki A, Leblanc M, Wei L, Fishbein MC, Czernin J, Mischel PS, Shaw RJ. LKB1 inactivation dictates therapeutic response of non-small cell lung cancer to the metabolism drug phenformin. Cancer Cell. 2013;23:143–58.PubMedPubMedCentralCrossRef
47.
Casas-Selves M, Kim J, Zhang Z, Helfrich BA, Gao D, Porter CC, Scarborough HA, Bunn Jr PA, Chan DC, Tan AC, DeGregori J. Tankyrase and the canonical Wnt pathway protect lung cancer cells from EGFR inhibition. Cancer Res. 2012;72:4154–64.PubMedPubMedCentralCrossRef
48.
Romero OA, Torres-Diz M, Pros E, Savola S, Gomez A, Moran S, Saez C, Iwakawa R, Villanueva A, Montuenga LM, et al. MAX inactivation in small cell lung cancer disrupts MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discov. 2014;4:292–303.PubMedCrossRef
49.
Kim N, Song M, Kim S, Seo Y, Kim Y, Yoon S. Differential regulation and synthetic lethality of exclusive RB1 and CDKN2A mutations in lung cancer. Int J Oncol. 2016;48:367–75.PubMed
50.
Bivona TG, Hieronymus H, Parker J, Chang K, Taron M, Rosell R, Moonsamy P, Dahlman K, Miller VA, Costa C, et al. FAS and NF-kappaB signalling modulate dependence of lung cancers on mutant EGFR. Nature. 2011;471:523–6.PubMedPubMedCentralCrossRef
51.
Blakely CM, Pazarentzos E, Olivas V, Asthana S, Yan JJ, Tan I, Hrustanovic G, Chan E, Lin L, Neel DS, et al. NF-kappaB-activating complex engaged in response to EGFR oncogene inhibition drives tumor cell survival and residual disease in lung cancer. Cell Rep. 2015;11:98–110.PubMedPubMedCentralCrossRef
52.
Sudo M, Mori S, Madan V, Yang H, Leong G, Koeffler HP. Short-hairpin RNA library: identification of therapeutic partners for gefitinib-resistant non-small cell lung cancer. Oncotarget. 2015;6:814–24.PubMedCrossRef
53.
Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, Greninger P, Brown RD, Godfrey JT, Cohoon TJ, et al. Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models. Cancer Cell. 2013;23:121–8.PubMedCrossRef
54.
Rajalingam K, Schreck R, Rapp UR, Albert S. Ras oncogenes and their downstream targets. Biochim Biophys Acta-Mol Cell Res. 2007;1773:1177–95.CrossRef
55.
Barault L, Lamba S, Di Nicolantonio F. Ras Mutations in Cancer. In eLS. John Wiley & Sons, Ltd; 2001.
56.
57.
Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, Wong KK, Elledge SJ. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. Cell. 2009;137:835–48.PubMedPubMedCentralCrossRef
58.
Scholl C, Frohling S, Dunn IF, Schinzel AC, Barbie DA, Kim SY, Silver SJ, Tamayo P, Wadlow RC, Ramaswamy S, et al. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell. 2009;137:821–34.PubMedCrossRef
59.
Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009;462:108-U122.
60.
Wang Y, Ngo VN, Marani M, Yang Y, Wright G, Staudt LM, Downward J. Critical role for transcriptional repressor Snail2 in transformation by oncogenic RAS in colorectal carcinoma cells. Oncogene. 2010;29:4658–70.PubMedCrossRef
61.
Costa-Cabral S, Brough R, Konde A, Aarts M, Campbell J, Marinari E, Riffell J, Bardelli A, Torrance C, Lord CJ, Ashworth A. CDK1 is a synthetic lethal target for KRAS mutant tumours. PLoS One. 2016;11:e0149099.PubMedPubMedCentralCrossRef
62.
Vicent S, Chen R, Sayles LC, Lin C, Walker RG, Gillespie AK, Subramanian A, Hinkle G, Yang X, Saif S, et al. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J Clin Invest. 2010;120:3940–52.PubMedPubMedCentralCrossRef
63.
Puyol M, Martin A, Dubus P, Mulero F, Pizcueta P, Khan G, Guerra C, Santamaria D, Barbacid M. A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma. Cancer Cell. 2010;18:63–73.PubMedCrossRef
64.
Kumar MS, Hancock DC, Molina-Arcas M, Steckel M, East P, Diefenbacher M, Armenteros-Monterroso E, Lassailly F, Matthews N, Nye E, et al. The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer. Cell. 2012;149:642–55.PubMedCrossRef
65.
Pourdehnad M, Truitt ML, Siddiqi IN, Ducker GS, Shokat KM, Ruggero D. Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers. Proc Natl Acad Sci U S A. 2013;110:11988–93.PubMedPubMedCentralCrossRef
66.
Yang D, Liu H, Goga A, Kim S, Yuneva M, Bishop JM. Therapeutic potential of a synthetic lethal interaction between the MYC proto-oncogene and inhibition of aurora-B kinase. Proc Natl Acad Sci U S A. 2010;107:13836–41.PubMedPubMedCentralCrossRef
67.
Kessler JD, Kahle KT, Sun T, Meerbrey KL, Schlabach MR, Schmitt EM, Skinner SO, Xu Q, Li MZ, Hartman ZC, et al. A SUMOylation-dependent transcriptional subprogram is required for Myc-driven tumorigenesis. Science. 2012;335:348–53.PubMedCrossRef
68.
Goga A, Yang D, Tward AD, Morgan DO, Bishop JM. Inhibition of CDK1 as a potential therapy for tumors over-expressing MYC. Nat Med. 2007;13:820–7.PubMedCrossRef
69.
Zuber J, Shi J, Wang E, Rappaport AR, Herrmann H, Sison EA, Magoon D, Qi J, Blatt K, Wunderlich M, et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature. 2011;478:524–8.PubMedPubMedCentralCrossRef
70.
Toyoshima M, Howie HL, Imakura M, Walsh RM, Annis JE, Chang AN, Frazier J, Chau BN, Loboda A, Linsley PS, et al. Functional genomics identifies therapeutic targets for MYC-driven cancer. Proc Natl Acad Sci U S A. 2012;109:9545–50.PubMedPubMedCentralCrossRef
71.
Zhou Z, Patel M, Ng N, Hsieh MH, Orth AP, Walker JR, Batalov S, Harris JL, Liu J. Identification of synthetic lethality of PRKDC in MYC-dependent human cancers by pooled shRNA screening. BMC Cancer. 2014;14:944.PubMedPubMedCentralCrossRef
72.
Li J, Bennett K, Stukalov A, Fang B, Zhang G, Yoshida T, Okamoto I, Kim JY, Song L, Bai Y, et al. Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms. Mol Syst Biol. 2013;9:705.PubMedPubMedCentralCrossRef
73.
Suda K, Tomizawa K, Mitsudomi T. Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation. Cancer Metastasis Rev. 2010;29:49–60.PubMedCrossRef
74.
Shigematsu H, Lin L, Takahashi T, Nomura M, Suzuki M, Wistuba II, Fong KM, Lee H, Toyooka S, Shimizu N, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst. 2005;97:339–46.PubMedCrossRef
75.
Kosaka T, Yatabe Y, Endoh H, Kuwano H, Takahashi T, Mitsudomi T. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res. 2004;64:8919–23.PubMedCrossRef
76.
Unni AM, Lockwood WW, Zejnullahu K, Lee-Lin SQ, Varmus H. Evidence that synthetic lethality underlies the mutual exclusivity of oncogenic KRAS and EGFR mutations in lung adenocarcinoma. Elife. 2015;4:e06907.PubMedPubMedCentralCrossRef
77.
Guo W, Wu S, Liu J, Fang B. Identification of a small molecule with synthetic lethality for K-ras and protein kinase C iota. Cancer Res. 2008;68:7403–8.PubMedPubMedCentralCrossRef
78.
Muller FL, Aquilanti EA, DePinho RA. Collateral lethality: a new therapeutic strategy in oncology. Trends Cancer. 2015;1:161–73.PubMedCrossRef
79.
Muller FL, Colla S, Aquilanti E, Manzo VE, Genovese G, Lee J, Eisenson D, Narurkar R, Deng P, Nezi L, et al. Passenger deletions generate therapeutic vulnerabilities in cancer. Nature. 2012;488:337–42.PubMedPubMedCentralCrossRef
80.
Hoffman GR, Rahal R, Buxton F, Xiang K, McAllister G, Frias E, Bagdasarian L, Huber J, Lindeman A, Chen D, et al. Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers. Proc Natl Acad Sci U S A. 2014;111:3128–33.PubMedPubMedCentralCrossRef
81.
Orvis T, Hepperla A, Walter V, Song S, Simon J, Parker J, Wilkerson MD, Desai N, Major MB, Hayes DN, et al. BRG1/SMARCA4 inactivation promotes non-small cell lung cancer aggressiveness by altering chromatin organization. Cancer Res. 2014;74:6486–98.PubMedPubMedCentralCrossRef
82.
Wilson BG, Helming KC, Wang X, Kim Y, Vazquez F, Jagani Z, Hahn WC, Roberts CW. Residual complexes containing SMARCA2 (BRM) underlie the oncogenic drive of SMARCA4 (BRG1) mutation. Mol Cell Biol. 2014;34:1136–44.PubMedPubMedCentralCrossRef
83.
Oike T, Ogiwara H, Tominaga Y, Ito K, Ando O, Tsuta K, Mizukami T, Shimada Y, Isomura H, Komachi M, et al. A synthetic lethality-based strategy to treat cancers harboring a genetic deficiency in the chromatin remodeling factor BRG1. Cancer Res. 2013;73:5508–18.PubMedCrossRef
84.
Barabas K, Milner R, Lurie D, Adin C. Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol. 2008;6:1–18.PubMedCrossRef
85.
Martin RW, Connell PP, Bishop DK. The yin and yang of treating BRCA-deficient tumors. Cell. 2008;132:919–20.PubMedCrossRef
86.
Arora S, Bisanz KM, Peralta LA, Basu GD, Choudhary A, Tibes R, Azorsa DO. RNAi screening of the kinome identifies modulators of cisplatin response in ovarian cancer cells. Gynecol Oncol. 2010;118:220–7.PubMedCrossRef
87.
Li X, Zhang L, Yu L, Wei W, Lin X, Hou X, Tian Y. shRNA-mediated AMBRA1 knockdown reduces the cisplatin-induced autophagy and sensitizes ovarian cancer cells to cisplatin. J Toxicol Sci. 2016;41:45–53.PubMedCrossRef
88.
Qian Z, Li M, Wang R, Xiao Q, Wang J, He D, Xiao X. Knockdown of CABYR-a/b increases chemosensitivity of human non-small cell lung cancer cells through inactivation of Akt. Mol Cancer Res. 2014;12:335–47.PubMedCrossRef
89.
Leung AW, Hung SS, Backstrom I, Ricaurte D, Kwok B, Poon S, McKinney S, Segovia R, Rawji J, Qadir MA, et al. Combined use of gene expression modeling and siRNA screening identifies genes and pathways which enhance the activity of cisplatin when added at no effect levels to non-small cell lung cancer cells in vitro. PLoS One. 2016;11:e0150675.PubMedPubMedCentralCrossRef
90.
Huntoon CJ, Flatten KS, Wahner Hendrickson AE, Huehls AM, Sutor SL, Kaufmann SH, Karnitz LM. ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status. Cancer Res. 2013;73:3683–91.PubMedPubMedCentralCrossRef
91.
Leung AW, Dragowska WH, Ricaurte D, Kwok B, Mathew V, Roosendaal J, Ahluwalia A, Warburton C, Laskin JJ, Stirling PC, et al. 3′-Phosphoadenosine 5′-phosphosulfate synthase 1 (PAPSS1) knockdown sensitizes non-small cell lung cancer cells to DNA damaging agents. Oncotarget. 2015;6:17161–77.PubMedPubMedCentralCrossRef
92.
Swanton C, Marani M, Pardo O, Warne PH, Kelly G, Sahai E, Elustondo F, Chang J, Temple J, Ahmed AA, et al. Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs. Cancer Cell. 2007;11:498–512.PubMedCrossRef
93.
De P, Sun Y, Carlson JH, Friedman LS, Leyland-Jones BR, Dey N. Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of PARP inhibitor in triple negative breast cancer model beyond BRCA-ness. Neoplasia. 2014;16:43–72.PubMedPubMedCentralCrossRef
94.
Cron KR, Zhu K, Kushwaha DS, Hsieh G, Merzon D, Rameseder J, Chen CC, D’Andrea AD, Kozono D. Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer. PLoS One. 2013;8:e73710.PubMedPubMedCentralCrossRef
95.
Neijzen R, Wong MQ, Gill N, Wang H, Karim T, Anantha M, Strutt D, Waterhouse D, Bally MB, Tai IT, et al. Irinophore C™, a lipid nanoparticulate formulation of irinotecan, improves vascular function, increases the delivery of sequentially administered 5-FU in HT-29 tumors, and controls tumor growth in patient derived xenografts of colon cancer. J Control Release. 2015;199:72–83.PubMedCrossRef
96.
Mayer LD, Harasym TO, Tardi PG, Harasym NL, Shew CR, Johnstone SA, Ramsay EC, Bally MB, Janoff AS. Ratiometric dosing of anticancer drug combinations: Controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice. Mol Cancer Ther. 2006;5:1854–63.PubMedCrossRef
97.
Ramsay EC, Dos Santos N, Dragowska WH, Laskin JJ, Bally MB. The formulation of lipid-based nanotechnologies for the delivery of fixed dose anticancer drug combinations. Curr Drug Deliv. 2005;2:341–51.PubMedCrossRef
98.
Patankar NA, Pritchard J, van Grinsven M, Osooly M, Bally MB. Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity. Clin Cancer Res. 2013;19:865–77.PubMedCrossRef
99.
Peters GJ, Bergman AM, van Haperen VW R, Veerman G, Kuiper CM, Braakhuis BJ. Interaction between cisplatin and gemcitabine in vitro and in vivo. Semin Oncol. 1995;22:72–9.PubMed
100.
Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002;346:85–91.PubMedCrossRef
101.
Harasym TO, Tardi PG, Johnstone SA, Bally MB, Janoff A, Mayer L. Fixed drug ratio liposome formulations of combination cancer therapeutics. Liposome Technology. 2006;3:25–48.
102.
Harasym TO, Liboiron BD, Mayer LD. Drug ratio-dependent antagonism: a new category of multidrug resistance and strategies for its circumvention. Methods Mol Biol. 2010;596:291–323.PubMedCrossRef
103.
Chou TC. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 2010;70:440–6.PubMedCrossRef
104.
Chang TT, Chou TC. Rational approach to the clinical protocol design for drug combinations: a review. Acta Paediatr Taiwan. 2000;41:294–302.PubMed
105.
Kang W, DiPaola RS, Vazquez A. Inference of synergy/antagonism between anticancer drugs from the pooled analysis of clinical trials. BMC Med Res Methodol. 2013;13:1–8.CrossRef
106.
Jackson AL, Linsley PS. Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application. Nat Rev Drug Discov. 2010;9:57–67.PubMedCrossRef
107.
Luo T, Masson K, Jaffe JD, Silkworth W, Ross NT, Scherer CA, Scholl C, Frohling S, Carr SA, Stern AM, et al. STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer cell viability. Proc Natl Acad Sci U S A. 2012;109:2860–5.PubMedPubMedCentralCrossRef
108.
Burckstummer T, Bennett KL, Preradovic A, Schutze G, Hantschel O, Superti-Furga G, Bauch A. An efficient tandem affinity purification procedure for interaction proteomics in mammalian cells. Nat Methods. 2006;3:1013–9.PubMedCrossRef
109.
Tsomaia N. Peptide therapeutics: targeting the undruggable space. Eur J Med Chem. 2015;94:459–70.PubMedCrossRef
110.
Mayer LD, Janoff AS. Optimizing combination chemotherapy by controlling drug ratios. Mol Interv. 2007;7:216–23.PubMedCrossRef
111.
Tardi PG, Dos Santos N, Harasym TO, Johnstone SA, Zisman N, Tsang AW, Bermudes DG, Mayer LD. Drug ratio-dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo. Mol Cancer Ther. 2009;8:2266–75.PubMedCrossRef
112.
Liboiron BD, Mayer LD. Nanoscale particulate systems for multidrug delivery: towards improved combination chemotherapy. Ther Deliv. 2014;5:149–71.PubMedCrossRef
113.
114.
Li T, Ling YH, Goldman ID, Perez-Soler R. Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in human non-small cell lung cancer cells. Clin Cancer Res. 2007;13:3413–22.PubMedCrossRef
115.
Hare JI, Neijzen RW, Anantha M, Dos Santos N, Harasym N, Webb MS, Allen TM, Bally MB, Waterhouse DN. Treatment of colorectal cancer using a combination of liposomal irinotecan (Irinophore C) and 5-fluorouracil. PLoS One. 2013;8:e62349.PubMedPubMedCentralCrossRef
116.
Oakman C, Francis PA, Crown J, Quinaux E, Buyse M, De Azambuja E, Vila MM, Andersson M, Nordenskjold B, Jakesz R, et al. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer-8-year results of the Breast International Group 02–98 phase III trial. Ann Oncol. 2013;24:1203–11.PubMedCrossRef
117.
118.
Mayer LD, Dougherty G, Harasym TO, Bally MB. The role of tumor-associated macrophages in the delivery of liposomal doxorubicin to solid murine fibrosarcoma tumors. J Pharmacol Exp Ther. 1997;280:1406–14.PubMed
119.
Chari R, Thu KL, Wilson IM, Lockwood WW, Lonergan KM, Coe BP, Malloff CA, Gazdar AF, Lam S, Garnis C, MacAulay CE, Alvarez CE, Lam LL. Integrating the multiple dimensions of genomic and epigenomic landscapes of cancer. Cancer and Metastasis Reviews. 2010;29(1):73–93.PubMedPubMedCentralCrossRef
120.
Abraham SA, Waterhouse DN, Mayer LD, Cullis PR, Madden TD, Bally MB. The liposomal formulation of doxorubicin. Methods Enzymol. 2005;391:71–97.PubMedCrossRef
Metadata
Title
Synthetic lethality in lung cancer and translation to clinical therapies
Authors
Ada W. Y. Leung
Tanya de Silva
Marcel B. Bally
William W. Lockwood
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2016
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-016-0546-y

Other articles of this Issue 1/2016

Molecular Cancer 1/2016 Go to the issue

Research

PKM2 promotes tumor angiogenesis by regulating HIF-1α through NF-κB activation

Research

STAT3 signaling drives EZH2 transcriptional activation and mediates poor prognosis in gastric cancer

Letter to the Editor

Small non-coding RNA biomarkers in sputum for lung cancer diagnosis

Review

Imaging metabolic heterogeneity in cancer

Research

Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism

Research

Pharmacological targeting of CXCL12/CXCR4 signaling in prostate cancer bone metastasis
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits