Skip to main content
SpringerLink
Log in

Pharmacogenomics of Antitumor Targeted Agent and Immunotherapy

  • Chapter
  • First Online:
Pharmacogenomics in Precision Medicine

  • 598 Accesses

Abstract

Currently, cancer incidence and mortality rapidly increase and have gradually become the leading cause of death in human disease. The main medications used in clinical cancer therapy can be categorized into three types according to the pharmacological mechanism and therapeutic target, including chemotherapeutic agents, molecule-targeted agents, and immunotherapeutic agents. Targeted therapy and immunotherapy are innovative approaches in cancer therapy that has been widely accepted, both of which possess several irreplaceable advantages compared to chemotherapy. The molecule-targeted agents, which are related to higher accurate and lower toxicity, are proposed against the molecular biological targets like tumor cell proliferation, angiogenesis, apoptosis, and tumor invasion. Immunotherapy has dramatically enhanced the prognosis of tumor patients and has greatly improved the treatment for those with advanced disease. Owing to the less toxicity as well as long-term curative effect, the application of immunotherapy continues to expand with multiple new agents approved in the clinical treatment. Several pharmacogenomic biomarkers have been applied to clinical anticancer treatment in effort to strengthen the patients’ treatment benefits and reduce potential side effects. This chapter systematically summarized the significant pharmacogenomic discoveries of some typical tumor therapeutic drugs involved in targeted therapy and immunotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Paez GJ, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M (2004) EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304:1497–1500. https://doi.org/10.1126/science.1099314

    Article  CAS  PubMed  Google Scholar 

  2. Kobayashi S, Boggon TJ, Dayaram T, Jänne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B (2005) EGFR mutation and resistance of non–small-cell lung cancer to gefitinib. New Engl J Med 352:786–792. https://doi.org/10.1056/nejmoa044238

    Article  CAS  PubMed  Google Scholar 

  3. Sordella R, Bell DW, Haber DA, Settleman J (2004) Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 305:1163–1167. https://doi.org/10.1126/science.1101637

    Article  CAS  PubMed  Google Scholar 

  4. Shih J-Y, Gow C-H, Yang P-C (2005) EGFR mutation conferring primary resistance to gefitinib in non–small-cell lung cancer. New Engl J Med 353:207–208. https://doi.org/10.1056/nejm200507143530217

    Article  CAS  PubMed  Google Scholar 

  5. Tartarone A, Lazzari C, Lerose R, Conteduca V, Improta G, Zupa A, Bulotta A, Aieta M, Gregorc V (2013) Mechanisms of resistance to EGFR tyrosine kinase inhibitors gefitinib/erlotinib and to ALK inhibitor crizotinib. Lung Cancer 81:328–336. https://doi.org/10.1016/j.lungcan.2013.05.020

    Article  PubMed  Google Scholar 

  6. Sharma SV, Bell DW, Settleman J, Haber DA (2007) Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 7:169–181. https://doi.org/10.1038/nrc2088

    Article  CAS  PubMed  Google Scholar 

  7. Normanno N, Denis MG, Thress KS, Ratcliffe M, Reck M (2017) Guide to detecting epidermal growth factor receptor (EGFR) mutations in ctDNA of patients with advanced non-small-cell lung cancer. Oncotarget 8:12501–12516. https://doi.org/10.18632/oncotarget.13915

    Article  PubMed  Google Scholar 

  8. Kobayashi Y, Azuma K, Nagai H, Kim Y, Togashi Y, Sesumi Y, Chiba M, Shimoji M, Sato K, Tomizawa K, Takemoto T, Nishio K, Mitsudomi T (2017) Characterization of EGFR T790M, L792F, and C797S mutations as mechanisms of acquired resistance to afatinib in lung cancer. Mol Cancer Ther 16:357–364. https://doi.org/10.1158/1535-7163.mct-16-0407

    Article  CAS  PubMed  Google Scholar 

  9. Cross D, Ashton SE, Ghiorghiu S, Eberlein C, Nebhan CA, Spitzler PJ, Orme JP, Finlay RM, Ward RA, Mellor MJ, Hughes G, Rahi A, Jacobs VN, Brewer M, Ichihara E, Sun J, Jin H, Ballard P, Katherine A-K, Rowlinson R, Klinowska T, Richmond G, Cantarini M, Kim D-W, Ranson MR, Pao W (2014) AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 4:1046–1061. https://doi.org/10.1158/2159-8290.cd-14-0337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chen K, Zhou F, Shen W, Jiang T, Wu X, Tong X, Shao YW, Qin S, Zhou C (2017) Novel mutations on EGFR Leu792 potentially correlate to acquired resistance to osimertinib in advanced NSCLC. J Thorac Oncol 12:e65–e68. https://doi.org/10.1016/j.jtho.2016.12.024

    Article  PubMed  Google Scholar 

  11. Wang S, Tsui ST, Liu C, Song Y, Liu D (2016) EGFR C797S mutation mediates resistance to third-generation inhibitors in T790M-positive non-small cell lung cancer. J Hematol Oncol 9:59. https://doi.org/10.1186/s13045-016-0290-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tan DSW, Yom SS, Tsao MS, Pass HI, Kelly K, Peled N, Yung RC, Wistuba II, Yatabe Y, Unger M, Mack PC, Wynes MW, Mitsudomi T, Weder W, Yankelevitz D, Herbst RS, Gandara DR, Carbone DP, Bunn PA, Mok TSK, Hirsch FR (2016) The International Association for the Study of lung cancer consensus statement on optimizing management of EGFR mutation–positive non–small cell lung cancer: status in 2016. J Thorac Oncol 11:946–963. https://doi.org/10.1016/j.jtho.2016.05.008

    Article  PubMed  Google Scholar 

  13. Choi Y, Soda M, Yamashita Y, Ueno T, Takashima J, Nakajima T, Yatabe Y, Takeuchi K, Hamada T, Haruta H, Ishikawa Y, Kimura H, Mitsudomi T, Tanio Y, Mano H, ALK Lung Cancer Study Group (2010) EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. New Engl J Med 363:1734–1739. https://doi.org/10.1056/NEJMoa1007478

    Article  CAS  PubMed  Google Scholar 

  14. Doebele RC, Pilling AB, Aisner DL, Kutateladze TG, Le AT, Weickhardt AJ, Kondo KL, Linderman DJ, Heasley LE, Franklin WA, Marileila V-G, Camidge RD (2012) Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non–small cell lung cancer. Clin Cancer Res 18:1472–1482. https://doi.org/10.1158/1078-0432.CCR-11-2906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Katayama R, Shaw AT, Khan TM, Mari M-K, Solomon BJ, Halmos B, Jessop NA, Wain JC, Yeo A, Benes C, Drew L, Saeh J, Crosby K, Sequist LV, Iafrate JA, Engelman JA (2012) Mechanisms of acquired crizotinib resistance in ALK-rearranged lung cancers. Sci Transl Med 4:120ra17. https://doi.org/10.1126/scitranslmed.3003316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cassier PA, Fumagalli E, Rutkowski P, Schöffski P, Glabbeke M, Maria D-R, Emile J-F, Duffaud F, Javier M-B, Landi B, Adenis A, Bertucci F, Bompas E, Bouché O, Leyvraz S, Judson I, Verweij J, Casali P, Blay J-Y, Hohenberger P, European Organisation for Research and Treatment of Cancer (2012) Outcome of patients with platelet-derived growth factor receptor alpha–mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Clin Cancer Res 18:4458–4464. https://doi.org/10.1158/1078-0432.CCR-11-3025

    Article  CAS  PubMed  Google Scholar 

  17. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, Leversha MA, Jeffrey PD, Desantis D, Singer S, Brennan MF, Maki RG, Ronald PD (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11:4182–4190. https://doi.org/10.1158/1078-0432.CCR-04-2245

    Article  CAS  PubMed  Google Scholar 

  18. Tamborini E, Pricl S, Negri T, Lagonigro M, Miselli F, Greco A, Gronchi A, Casali P, Ferrone M, Fermeglia M, Carbone A, Pierotti M, Pilotti S (2006) Functional analyses and molecular modeling of two c-kit mutations responsible for imatinib secondary resistance in GIST patients. Oncogene 25:1209639. https://doi.org/10.1038/sj.onc.1209639

    Article  CAS  Google Scholar 

  19. Srivastava S, Dutt S (2013) Imatinib mesylate resistance and mutations: an Indian experience. Indian J Med Paediatr Oncol 34:213–220. https://doi.org/10.4103/0971-5851.123748

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11:21–28. https://doi.org/10.1016/s1470-2045(09)70311-0

    Article  CAS  PubMed  Google Scholar 

  21. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer H-R, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. New Engl J Med 359:1116–1127. https://doi.org/10.1056/nejmoa0802656

    Article  CAS  PubMed  Google Scholar 

  22. Gao J, Wang T, Yu J, Li Y, Shen L (2011) Wild-type KRAS and BRAF could predict response to cetuximab in Chinese colorectal cancer patients. Chin J Cancer Res 23:271–275. https://doi.org/10.1007/s11670-011-0271-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kjersem JB, Skovlund E, Ikdahl T, Guren T, Kersten C, Dalsgaard AM, Yilmaz MK, Fokstuen T, Tveit KM, Kure EH (2014) FCGR2A and FCGR3A polymorphisms and clinical outcome in metastatic colorectal cancer patients treated with first-line 5-fluorouracil/folinic acid and oxaliplatin +/− cetuximab. BMC Cancer 14:340. https://doi.org/10.1186/1471-2407-14-340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Brower V (2016) SNP affects colorectal cancer outcomes with cetuximab. Lancet Oncol. 17:e230. https://doi.org/10.1016/S1470-2045(16)30163-2

    Article  PubMed  Google Scholar 

  25. Pfisterer K, Fusi A, Klinghammer K, Knödler M, Nonnenmacher A, Keilholz U (2015) PI3K/PTEN/AKT/mTOR polymorphisms: association with clinical outcome in patients with head and neck squamous cell carcinoma receiving cetuximab-docetaxel. Head Neck 37:471–478. https://doi.org/10.1002/hed.23604

    Article  PubMed  Google Scholar 

  26. Froelich MF, Stintzing S, Kumbrink J, Grünewald T, Mansmann U, Heinemann V, Kirchner T, Jung A (2018) The DNA-polymorphism rs849142 is associated with skin toxicity induced by targeted anti-EGFR therapy using cetuximab. Oncotarget 9:30279–30288. https://doi.org/10.18632/oncotarget.25689

    Article  PubMed  PubMed Central  Google Scholar 

  27. Doi T, Ohtsu A, Tahara M, Tamura T, Shirao K, Yamada Y, Otani S, Yang B-B, Ohkura M, Ohtsu T (2009) Safety and pharmacokinetics of panitumumab in Japanese patients with advanced solid tumors. Int J Clin Oncol 14:307–314. https://doi.org/10.1007/s10147-008-0855-2

    Article  CAS  PubMed  Google Scholar 

  28. Wang Y, Wang H, Jiang Y, Zhang Y, Wang X (2017) A randomized phase III study of combining erlotinib with bevacizumab and panitumumab versus erlotinib alone as second-line therapy for Chinese patients with non-small-cell lung cancer. Biomed Pharmacother 89:875–879. https://doi.org/10.1016/j.biopha.2017.02.097

    Article  CAS  PubMed  Google Scholar 

  29. Therkildsen C, Bergmann TK, Tine H-S, Ladelund S, Nilbert M (2014) The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: a systematic review and meta-analysis. Acta Oncol 53:852–864. https://doi.org/10.3109/0284186x.2014.895036

    Article  CAS  PubMed  Google Scholar 

  30. Bonin S, Donada M, Bussolati G, Nardon E, Annaratone L, Pichler M, Chiaravalli A, Capella C, Hoefler G, Stanta G (2016) A synonymous EGFR polymorphism predicting responsiveness to anti-EGFR therapy in metastatic colorectal cancer patients. Tumor Biol 37:7295–7303. https://doi.org/10.1007/s13277-015-4543-3

    Article  CAS  Google Scholar 

  31. Hou Y, Nitta H, Wei L, Banks PM, Portier B, Parwani AV, Li Z (2017) HER2 intratumoral heterogeneity is independently associated with incomplete response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma. Breast Cancer Res Treat 166:447–457. https://doi.org/10.1007/s10549-017-4453-8

    Article  CAS  PubMed  Google Scholar 

  32. Sperinde J, Jin X, Banerjee J, Penuel E, Saha A, Diedrich G, Huang W, Leitzel K, Weidler J, Ali SM, Fuchs E-M, Singer CF, Köstler WJ, Bates M, Parry G, Winslow J, Lipton A (2010) Quantitation of p95HER2 in paraffin sections by using a p95-specific antibody and correlation with outcome in a cohort of trastuzumab-treated breast cancer patients. Clin Cancer Res 16:4226–4235. https://doi.org/10.1158/1078-0432.ccr-10-0410

    Article  CAS  PubMed  Google Scholar 

  33. Chandarlapaty S, Sakr RA, Giri D, Patil S, Heguy A, Morrow M, Modi S, Norton L, Rosen N, Hudis C, King TA (2012) Frequent mutational activation of the PI3K-AKT pathway in trastuzumab-resistant breast cancer. Clin Cancer Res 18:6784–6791. https://doi.org/10.1158/1078-0432.CCR-12-1785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dave B, Migliaccio I, Gutierrez CM, Wu M-F, Chamness GC, Wong H, Narasanna A, Chakrabarty A, Hilsenbeck SG, Huang J, Rimawi M, Schiff R, Arteaga C, Osborne KC, Chang JC (2010) Loss of phosphatase and tensin homolog or phosphoinositol-3 kinase activation and response to trastuzumab or lapatinib in human epidermal growth factor receptor 2–overexpressing locally advanced breast cancers. J Clin Oncol 29:166–173. https://doi.org/10.1200/jco.2009.27.7814

    Article  PubMed  PubMed Central  Google Scholar 

  35. Johnston S, Hegg R, Im S-A, Park I, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S, Sarp S, Izquierdo MA, Williams LS, Gradishar WJ (2017) Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with her2-positive, hormone receptor–positive metastatic breast cancer: ALTERNATIVE. J Clin Oncol 36:741–748. https://doi.org/10.1200/jco.2017.74.7824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sledge GW, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, Koh H, Grischke E-MM, Frenzel M, Lin Y, Barriga S, Smith IC, Bourayou N, Antonio L-C (2017) MONARCH 2: abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol 35:2875–2884. https://doi.org/10.1200/JCO.2017.73.7585

    Article  CAS  PubMed  Google Scholar 

  37. Scheuer W, Friess T, Burtscher H, Bossenmaier B, Endl J, Hasmann M (2009) Strongly enhanced antitumor activity of trastuzumab and pertuzumab combination treatment on her2-positive human xenograft tumor models. Cancer Res 69:9330–9336. https://doi.org/10.1158/0008-5472.CAN-08-4597

    Article  CAS  PubMed  Google Scholar 

  38. Si L, Zhang X, Xu Z, Jiang Q, Bu L, Wang X, Mao L, Zhang W, Richie N, Guo J (2018) Vemurafenib in Chinese patients with BRAFV600 mutation-positive unresectable or metastatic melanoma: an open-label, multicenter phase I study. BMC Cancer 18:520. https://doi.org/10.1186/s12885-018-4336-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lito P, Rosen N, Solit DB (2013) Tumor adaptation and resistance to RAF inhibitors. Nat Med 19(11):1401. https://doi.org/10.1038/nm.3392

    Article  CAS  PubMed  Google Scholar 

  40. Chapman P, Robert C, Larkin J, Haanen J, Ribas A, Hogg D, Hamid O, Ascierto P, Testori A, Lorigan P, Dummer R, Sosman J, Flaherty K, Chang I, Coleman S, Caro I, Hauschild A, McArthur GA (2017) Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study. Ann Oncol 28:2581–2587. https://doi.org/10.1093/annonc/mdx339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gupta R, Bugide S, Wang B, Green MR, Johnson DB, Wajapeyee N (2019) Loss of BOP1 confers resistance to BRAF kinase inhibitors in melanoma by activating MAP kinase pathway. Proc Natl Acad Sci U S A 116:4583–4591. https://doi.org/10.1073/pnas.1821889116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hertzman Johansson C, Egyhazi Brage S (2014) BRAF inhibitors in cancer therapy. Pharmacol Ther 142:176–182. https://doi.org/10.1016/j.pharmthera.2013.11.011

    Article  CAS  PubMed  Google Scholar 

  43. Smith MP, Brunton H, Rowling EJ, Ferguson J, Arozarena I, Miskolczi Z, Lee JL, Girotti MR, Marais R, Levesque MP, Dummer R, Frederick DT, Flaherty KT, Cooper ZA, Wargo JA, Wellbrock C (2016) Inhibiting drivers of non-mutational drug tolerance is a salvage strategy for targeted melanoma therapy. Cancer Cell 29:270–284. https://doi.org/10.1016/j.ccell.2016.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hauschild A, Grob J-J, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH, Kaempgen E, Salvador M-A, Karaszewska B, Mauch C, Vanna C-S, Martin A-M, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB (2012) Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 380:358–365. https://doi.org/10.1016/s0140-6736(12)60868-x

    Article  CAS  PubMed  Google Scholar 

  45. Fujiwara Y, Yamazaki N, Kiyohara Y, Yoshikawa S, Yamamoto N, Tsutsumida A, Nokihara H, Namikawa K, Mukaiyama A, Zhang F, Tamura T (2018) Safety, tolerability, and pharmacokinetic profile of dabrafenib in Japanese patients with BRAF V600 mutation-positive solid tumors: a phase 1 study. Investig New Drugs 36:259–268. https://doi.org/10.1007/s10637-017-0502-8

    Article  CAS  Google Scholar 

  46. Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Vanna C-S, Dutriaux C, de Groot JB, Yamazaki N, Loquai C, Parseval LA, Pickard MD, Sandor V, Robert C, Flaherty KT (2018) Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 19:603–615. https://doi.org/10.1016/s1470-2045(18)30142-6

    Article  CAS  PubMed  Google Scholar 

  47. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, Demidov LV, Hassel JC, Rutkowski P, Mohr P, Dummer R, Trefzer U, Larkin JM, Utikal J, Dreno B, Nyakas M, Middleton MR, Becker JC, Casey M, Sherman LJ, Wu FS, Ouellet D, Martin A-M, Patel K, Schadendorf D, METRIC Study Group (2012) Improved survival with MEK inhibition in BRAF-mutated melanoma. New Engl J Med 367:107–114. https://doi.org/10.1056/nejmoa1203421

    Article  CAS  PubMed  Google Scholar 

  48. Schreuer M, Jansen Y, Planken S, Chevolet I, Seremet T, Kruse V, Neyns B (2017) Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAF V600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial. Lancet Oncol 18:464–472. https://doi.org/10.1016/s1470-2045(17)30171-7

    Article  CAS  PubMed  Google Scholar 

  49. Planchard D, Besse B, Groen HJ, Souquet P-J, Quoix E, Baik CS, Barlesi F, Kim T, Mazieres J, Novello S, Rigas JR, Upalawanna A, Anthony MD, Zhang P, Mookerjee B, Johnson BE (2016) Dabrafenib plus trametinib in patients with previously treated BRAF V600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol 17:984–993. https://doi.org/10.1016/s1470-2045(16)30146-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Rechem C, Black JC, Greninger P, Zhao Y, Donado C, Burrowes P, Ladd B, Christiani DC, Benes CH, Whetstine JR (2015) A coding single-nucleotide polymorphism in lysine demethylase KDM4A associates with increased sensitivity to mTOR inhibitors. Cancer Discov 5:245–254. https://doi.org/10.1158/2159-8290.cd-14-1159

    Article  PubMed  PubMed Central  Google Scholar 

  51. Guo J, Huang Y, Zhang X, Zhou F, Sun Y, Qin S, Ye Z, Wang H, Jappe A, Straub P, Pirotta N, Gogov S (2013) Safety and efficacy of everolimus in Chinese patients with metastatic renal cell carcinoma resistant to vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy: an open-label phase 1b study. BMC Cancer 13:136. https://doi.org/10.1186/1471-2407-13-136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Husen P, Straub K, Willuweit K, Hagemann A, Wedemeyer H, Bachmann HS, Herzer K (2019) SNPs within the MTOR gene are associated with an increased risk of developing De Novo diabetes mellitus following the administration of everolimus in liver transplant recipients. Transplant Proc 51:1962–1971. https://doi.org/10.1016/j.transproceed.2019.03.027

    Article  CAS  PubMed  Google Scholar 

  53. Owen AO, Horwitz S, Masszi T, Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi M, Walewski J, Savage K, Foss F, Allen LF, Shustov A (2015) Belinostat in patients with relapsed or refractory peripheral t-cell lymphoma: results of the pivotal phase II belief (CLN-19) study. J Clin Oncol 33:2492–2499. https://doi.org/10.1200/jco.2014.59.2782

    Article  Google Scholar 

  54. Luu T, Kim K, Blanchard S, Anyang B, Hurria A, Yang L, Beumer JH, Somlo G, Yen Y (2018) Phase IB trial of ixabepilone and vorinostat in metastatic breast cancer. Breast Cancer Res Treat 167:469–478. https://doi.org/10.1007/s10549-017-4516-x

    Article  CAS  PubMed  Google Scholar 

  55. Chen DS, Mellman I (2017) Elements of cancer immunity and the cancer–immune set point. Nature 541:321. https://doi.org/10.1038/nature21349

    Article  CAS  PubMed  Google Scholar 

  56. Tang H, Liang Y, Anders RA, Taube JM, Qiu X, Mulgaonkar A, Liu X, Harrington SM, Guo J, Xin Y, Xiong Y, Nham K, Silvers W, Hao G, Sun X, Chen M, Hannan R, Qiao J, Dong H, Peng H, Fu Y-X (2018) PD-L1 on host cells is essential for PD-L1 blockade–mediated tumor regression. J Clin Invest 128:580–588. https://doi.org/10.1172/jci96061

    Article  PubMed  PubMed Central  Google Scholar 

  57. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder J, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn M-J, Felip E, Lee J-S, Hellmann MD, Hamid O, Goldman JW, Soria J-C, Marisa D-F, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L, Investigators K-001 (2015) Pembrolizumab for the treatment of non–small-cell lung cancer. New Engl J Med 372:2018–2028. https://doi.org/10.1056/nejmoa1501824

    Article  PubMed  Google Scholar 

  58. Herbst RS, Baas P, Kim D-W, Felip E, P-G José L, Han J-Y, Molina J, Kim J-H, Arvis C, Ahn M-J, Majem M, Fidler MJ, de Castro G, Garrido M, Lubiniecki GM, Shentu Y, Im E, Marisa D-F, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet 387:1540–1550. https://doi.org/10.1016/s0140-6736(15)01281-7

    Article  CAS  PubMed  Google Scholar 

  59. Reck M, Delvys R-A, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, Mary O, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR, Investigators K-024 (2016) Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. New Engl J Med 375:1823–1833. https://doi.org/10.1056/NEJMoa1606774

    Article  CAS  PubMed  Google Scholar 

  60. Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Caliò A, Cuppone F, Sperduti I, Giannarelli D, Chilosi M, Bronte V, Scarpa A, Bria E, Tortora G (2015) Differential activity of nivolumab, pembrolizumab and MPDL3280A according to the tumor expression of programmed death-ligand-1 (PD-L1): sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS One 10:e0130142. https://doi.org/10.1371/journal.pone.0130142

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Motzer RJ, Escudier B, David FM, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu L-A, Waxman IM, Sharma P, Investigators C (2015) Nivolumab versus everolimus in advanced renal-cell carcinoma. New Engl J Med 373:1803–1813. https://doi.org/10.1056/nejmoa1510665

    Article  CAS  PubMed  Google Scholar 

  62. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols M, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera O, Marinis F, Turna H, Lee J-S, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR, Group O (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389:255–265. https://doi.org/10.1016/S0140-6736(16)32517-X

    Article  PubMed  Google Scholar 

  63. Joseph M, Han G, Schalper KA, Daniel C-H, Pelakanou V, Rehman J, Velcheti V, Herbst R, Patricia L, Rimm DL (2015) Quantitative assessment of the heterogeneity of PD-L1 expression in non–small-cell lung cancer. JAMA Oncol 2:1–9. https://doi.org/10.1001/jamaoncol.2015.3638

    Article  Google Scholar 

  64. Yarchoan M, Hopkins A, Jaffee EM (2017) Tumor mutational burden and response rate to PD-1 inhibition. N Engl J Med. 377(25):2500–2501. https://doi.org/10.1056/NEJMc1713444

    Article  PubMed  PubMed Central  Google Scholar 

  65. Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, Stephens PJ, Daniels GA, Kurzrock R (2017) Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther 16(11):2598–2600. https://doi.org/10.1158/1535-7163.mct-17-0386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Rizvi H, Francisco S-V, La K, Chatila W, Jonsson P, Halpenny D, Plodkowski A, Long N, Sauter JL, Rekhtman N, Hollmann T, Schalper KA, Gainor JF, Shen R, Ni A, Arbour KC, Merghoub T, Wolchok J, Snyder A, Chaft JE, Kris MG, Rudin CM, Socci ND, Berger MF, Taylor BS, Zehir A, Solit DB, Arcila ME, Ladanyi M, Riely GJ, Schultz N, Hellmann MD (2018) Molecular determinants of response to anti–programmed cell death (PD)-1 and anti–programmed death-ligand (PD-L)-ligand 1 blockade in patients with non–small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol 36(7):633–641. https://doi.org/10.1200/JCO.2017.75.3384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA (2015) Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 348:124–128. https://doi.org/10.1126/science.aaa1348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Łuksza M, Riaz N, Makarov V, Balachandran VP, Hellmann MD, Solovyov A, Rizvi NA, Merghoub T, Levine AJ, Chan TA, Wolchok JD, Greenbaum BD (2017) A neoantigen fitness model predicts tumour response to checkpoint blockade immunotherapy. Nature 551:517. https://doi.org/10.1038/nature24473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Uryvaev A, Passhak M, Hershkovits D, Sabo E, Gil B-S (2018) The role of tumor-infiltrating lymphocytes (TILs) as a predictive biomarker of response to anti-PD1 therapy in patients with metastatic non-small cell lung cancer or metastatic melanoma. Med Oncol 35:25. https://doi.org/10.1007/s12032-018-1080-0

    Article  CAS  PubMed  Google Scholar 

  70. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang S, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA (2017) Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 357:409–413. https://doi.org/10.1126/science.aan6733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lemery S, Keegan P, Pazdur R (2017) First FDA approval agnostic of Cancer site — when a biomarker defines the indication. New Engl J Med 377:1409–1412. https://doi.org/10.1056/nejmp1709968

    Article  PubMed  Google Scholar 

  72. Peters S, Gettinger S, Johnson ML, Jänne PA, Garassino MC, Christoph D, Toh C, Rizvi NA, Chaft JE, Costa E, Patel JD, Chow L, Koczywas M, Ho C, Früh M, van den Heuvel M, Rothenstein J, Reck M, Luis P-A, Shepherd FA, Kurata T, Li Z, Qiu J, Kowanetz M, Mocci S, Shankar G, Sandler A, Felip E (2017) Phase II trial of atezolizumab as first-line or subsequent therapy for patients with programmed death-ligand 1–selected advanced non–small-cell lung cancer (BIRCH). J Clin Oncol 35:2781–2789. https://doi.org/10.1200/JCO.2016.71.9476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, Ali SM, Elvin JA, Singal G, Ross JS, Fabrizio D, Szabo PM, Chang H, Sasson A, Srinivasan S, Kirov S, Szustakowski J, Vitazka P, Edwards R, Bufill JA, Sharma N, Ou S-HI, Peled N, Spigel DR, Rizvi H, Aguilar E, Carter BW, Erasmus J, Halpenny DF, Plodkowski AJ, Long NM, Nishino M, Denning WL, Ana G-C, Hamdi H, Hirz T, Tong P, Wang J, Jaime R-C, Villalobos PA, Parra ER, Kalhor N, Sholl LM, Sauter JL, Jungbluth AA, Mari M-K, Azimi R, Elamin YY, Zhang J, Leonardi GC, Jiang F, Wong K-K, Lee JJ, Papadimitrakopoulou VA, Wistuba II, Miller VA, Frampton GM, Wolchok JD, Shaw AT, Jänne PA, Stephens PJ, Rudin CM, Geese WJ, Albacker LA, Heymach JV (2018) STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov 8:822–835. https://doi.org/10.1158/2159-8290.cd-18-0099

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Joshi AD, Hegde GV, Dickinson JD, Mittal AK, Lynch JC, Eudy JD, Armitage JO, Bierman PJ, Bociek GR, Devetten MP, Vose JM, Joshi SS (2007) ATM, CTLA4, MNDA, and HEM1 in high versus low CD38–expressing B-cell chronic lymphocytic leukemia. Clin Cancer Res 13:5295–5304. https://doi.org/10.1158/1078-0432.ccr-07-0283

    Article  CAS  PubMed  Google Scholar 

  75. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggeman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD, Chan TA (2014) Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371:2189–2199. https://doi.org/10.1056/nejmoa1406498

    Article  PubMed  PubMed Central  Google Scholar 

  76. Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, Sucker A, Hillen U, Foppen MH, Goldinger SM, Utikal J, Hassel JC, Weide B, Kaehler KC, Loquai C, Mohr P, Gutzmer R, Dummer R, Gabriel S, Wu CJ, Schadendorf D, Garraway LA (2015) Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 350:207–211. https://doi.org/10.1126/science.aad0095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wu X, Anita G-H, Liao X, Connelly C, Connolly EM, Li J, Manos MP, Lawrence D, David M, Severgnini M, Zhou J, Gjini E, Lako A, Lipschitz M, Pak CJ, Abdelrahman S, Rodig S, Hodi SF (2017) Angiopoietin-2 as a biomarker and target for immune checkpoint therapy. Cancer Immunol Res 5:17–28. https://doi.org/10.1158/2326-6066.cir-16-0206

    Article  CAS  PubMed  Google Scholar 

  78. Khoja L, Atenafu EG, Templeton A, Qye Y, Chappell M, Saibil S, Hogg D, Butler MO, Joshua AM (2016) The full blood count as a biomarker of outcome and toxicity in ipilimumab-treated cutaneous metastatic melanoma. Cancer Med 5:2792–2799. https://doi.org/10.1002/cam4.878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Max H-W, Rocha P, Arpi O, Taus Á, Nonell L, Durán X, Villanueva X, Deborah J-P, Nolan L, Danson S, Griffiths R, Miguel L-B, Rovira A, Albanell J, Ottensmeier C, Arriola E (2019) Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer. Onco Targets Ther 8:e1593810. https://doi.org/10.1080/2162402x.2019.1593810

    Article  CAS  Google Scholar 

  80. Almåsbak H, Aarvak T, Vemuri MC (2016) CAR T cell therapy: a game changer in cancer treatment. J Immunol Res 2016:5474602. https://doi.org/10.1155/2016/5474602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kosmaczewska A, Ciszak L, Suwalska K, Wolowiec D, Frydecka I (2005) CTLA-4 overexpression in CD19+/CD5+ cells correlates with the level of cell cycle regulators and disease progression in B-CLL patients. Leukemia 19:301–304. https://doi.org/10.1038/sj.leu.2403588

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, China

    Zhaoqian Liu, Chenxue Mao & Jiye Yin

Authors
  1. Zhaoqian Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chenxue Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiye Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhaoqian Liu .

Editor information

Editors and Affiliations

  1. School of Pharmacy, Fudan University, Shanghai, Shanghai, China

    Weimin Cai

  2. Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhaoqian Liu

  3. School of Pharmacy, Suzhou University, Suzhou, Jiangsu, China

    Liyan Miao

  4. School of Pharmacy, Fudan University, Shanghai, Shanghai, China

    Xiaoqiang Xiang

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Liu, Z., Mao, C., Yin, J. (2020). Pharmacogenomics of Antitumor Targeted Agent and Immunotherapy. In: Cai, W., Liu, Z., Miao, L., Xiang, X. (eds) Pharmacogenomics in Precision Medicine. Springer, Singapore. https://doi.org/10.1007/978-981-15-3895-7_4

Download citation

Publish with us

Policies and ethics

Search

Navigation