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Biomarkers

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Practical Medical Oncology Textbook

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Abstract

In the era of personalized medicine, biomarkers represent an irreplaceable tool for cancer screening, diagnosis, and management. As molecular biology techniques rapidly improve, several potential biomarkers have been discovered resulting in major changes in routine clinical practice and therefore shifting from an empirical therapy to a tailored and personalized medicine with the development of targeted therapies. Besides the predictive role enabling clinicians to select the right therapy for the right patient, biomarkers have turned to be irreplaceable in the management of cancer patients in terms of risk stratification (risk markers), prognosis (prognostic markers), and diagnosis (diagnostic markers). Moreover, validation of biomarkers as surrogate endpoints (which might stand in for and not replace a clinical endpoint) has recently become highly relevant in translational cancer research, leading physicians to design more robust and economically affordable clinical trials. The aim of this chapter is to outline all of these aspects while providing examples of the most common and clinically useful biomarkers.

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References

  1. Duffy MJ, Walsh S, McDermott EW, Crown J. Biomarkers in breast cancer: where are we and where are we going? Adv Clin Chem. 2015;71:1–23. https://doi.org/10.1016/bs.acc.2015.05.001.

    Article  CAS  PubMed  Google Scholar 

  2. Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS. 2010;5(6):463–6. https://doi.org/10.1097/COH.0b013e32833ed177.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Russo A, Incorvaia L, Del Re M, et al. The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM-SIAPEC-IAP-SIBioC-SIC-SIF Italian scientific societies. ESMO Open. 2021;6(3):100164. https://doi.org/10.1016/j.esmoop.2021.100164.

  4. Buonaguro FM, Pauza CD, Tornesello ML, Hainaut P, Franco R, Tommasino M. Cancer diagnostic and predictive biomarkers 2016. Biomed Res Int. 2017;2017:1–2. https://doi.org/10.1155/2017/7362721.

    Article  CAS  Google Scholar 

  5. Yan L, Zhang W. Precision medicine becomes reality-tumor type-agnostic therapy. Cancer Commun. 2018;38(1):6. https://doi.org/10.1186/s40880-018-0274-3.

    Article  Google Scholar 

  6. Yoshino T, Pentheroudakis G, Mishima S, Overman MJ, Yeh KH, Baba E et al. JSCO—ESMO—ASCO—JSMO—TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions. Ann Oncol. 2020. https://doi.org/10.1016/j.annonc.2020.03.299.

  7. Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors. Clin Cancer Res. 2019;25(13):3753–8. https://doi.org/10.1158/1078-0432.ccr-18-4070.

    Article  CAS  PubMed  Google Scholar 

  8. Demetri GD, Paz-Ares L, Farago AF, Liu SV, Chawla SP, Tosi D, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive tumours: pooled analysis of STARTRK-2, STARTRK-1, and ALKA-372-001. Ann Oncol. 2018;29:ix175. https://doi.org/10.1093/annonc/mdy483.003.

    Article  Google Scholar 

  9. Laetsch TW, DuBois SG, Mascarenhas L, Turpin B, Federman N, Albert CM, et al. Larotrectinib for paediatric solid tumours harbouring NTRK gene fusions: phase 1 results from a multicentre, open-label, phase 1/2 study. Lancet Oncol. 2018;19(5):705–14. https://doi.org/10.1016/s1470-2045(18)30119-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rolfo C, Ruiz R, Giovannetti E, Gil-Bazo I, Russo A, Passiglia F, et al. Entrectinib: a potent new TRK, ROS1, and ALK inhibitor. Expert Opin Investig Drugs. 2015;24(11):1493–500. https://doi.org/10.1517/13543784.2015.1096344.

    Article  CAS  PubMed  Google Scholar 

  11. Tao JJ, Schram AM, Hyman DM. Basket studies: redefining clinical trials in the era of genome-driven oncology. Annu Rev Med. 2018;69(1):319–31. https://doi.org/10.1146/annurev-med-062016-050343.

    Article  CAS  PubMed  Google Scholar 

  12. Ku CS. Clinical relevance of cancer genome sequencing. World J Gastroenterol. 2013;19(13):2011. https://doi.org/10.3748/wjg.v19.i13.2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Stäehler CF, Keller A, Leidinger P, Backes C, Chandran A, Wischhusen J, et al. Whole miRNome-wide differential co-expression of MicroRNAs. Genomics Proteomics Bioinformatics. 2012;10(5):285–94. https://doi.org/10.1016/j.gpb.2012.08.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sethi S, Ali S, Philip P, Sarkar F. Clinical advances in molecular biomarkers for cancer diagnosis and therapy. Int J Mol Sci. 2013;14(7):14771–84. https://doi.org/10.3390/ijms140714771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu ET. Molecular oncodiagnostics: where we are and where we need to go. J Clin Oncol. 2003;21(11):2052–5. https://doi.org/10.1200/jco.2003.01.137.

    Article  CAS  PubMed  Google Scholar 

  16. Kitkumthorn N, Mutirangura A. Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications. Clin Epigenetics. 2011;2(2):315–30. https://doi.org/10.1007/s13148-011-0032-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lao VV, Grady WM. Epigenetics and colorectal cancer. Nat Rev Gastroenterol Hepatol. 2011;8(12):686–700. https://doi.org/10.1038/nrgastro.2011.173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Scholler N, Urban N. CA125 in ovarian cancer. Biomark Med. 2007;1(4):513–23. https://doi.org/10.2217/17520363.1.4.513.

    Article  CAS  PubMed  Google Scholar 

  19. Bottoni P, Scatena R. The role of CA 125 as tumor marker: biochemical and clinical aspects. Adv Exp Med Boil. 2015;867:229–44. https://doi.org/10.1007/978-94-017-7215-0_14.

    Article  CAS  Google Scholar 

  20. Kang S, Kim T-J, Nam B-H, Seo S-S, Kim B-G, Bae D-S, et al. Preoperative serum CA-125 levels and risk of suboptimal cytoreduction in ovarian cancer: a meta-analysis. J Surg Oncol. 2010;101(1):13–7. https://doi.org/10.1002/jso.21398.

    Article  CAS  PubMed  Google Scholar 

  21. Chi DS, Zivanovic O, Palayekar MJ, Eisenhauer EL, Abu-Rustum NR, Sonoda Y, et al. A contemporary analysis of the ability of preoperative serum CA-125 to predict primary cytoreductive outcome in patients with advanced ovarian, tubal and peritoneal carcinoma. Gynecol Oncol. 2009;112(1):6–10. https://doi.org/10.1016/j.ygyno.2008.10.010.

    Article  CAS  PubMed  Google Scholar 

  22. van Altena AM, Holtsema H, Hendriks JC, Massuger LF, de Hullu JA. Cancer antigen 125 level after a bilateral salpingo-oophorectomy. Menopause. 2011;18(2):133–7. https://doi.org/10.1097/gme.0b013e3181ecfb51.

    Article  PubMed  Google Scholar 

  23. Gori S, Barberis M, Bella MA, et al. Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives. Crit Rev Oncol Hematol. 2019;140:67–72. https://doi.org/10.1016/j.critrevonc.2019.05.012.

  24. Pannek J, Marks LS, Pearson JD, Rittenhouse HG, Chan DW, Shery ED, et al. Influence of finasteride on free and total serum prostate specific antigen levels in men with benign prostatic hyperplasia. J Urol. 1998;159(2):449–53. https://doi.org/10.1016/s0022-5347(01)63946-6.

    Article  CAS  PubMed  Google Scholar 

  25. Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet. 2014;384(9959):2027–35. https://doi.org/10.1016/s0140-6736(14)60525-0.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Roach M, Hanks G, Thames H, Schellhammer P, Shipley WU, Sokol GH, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phy. 2006;65(4):965–74. https://doi.org/10.1016/j.ijrobp.2006.04.029.

    Article  Google Scholar 

  27. Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D’Amico AV, Dmochowski RR, et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association prostate guidelines for localized prostate cancer update panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol. 2007;177(2):540–5. https://doi.org/10.1016/j.juro.2006.10.097.

    Article  CAS  PubMed  Google Scholar 

  28. Thuret R, Massard C, Gross-Goupil M, Escudier B, Di Palma M, Bossi A, et al. The postchemotherapy PSA surge syndrome. Ann Oncol. 2008;19(7):1308–11. https://doi.org/10.1093/annonc/mdn062.

    Article  CAS  PubMed  Google Scholar 

  29. Ballman KV. Biomarker: predictive or prognostic? J Clin Oncol. 2015;33(33):3968–71. https://doi.org/10.1200/jco.2015.63.3651.

    Article  CAS  PubMed  Google Scholar 

  30. Lo Nigro C, Ricci V, Vivenza D, Granetto C, Fabozzi T, Miraglio E, et al. Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy. World J Gastroenterol. 2016;22(30):6944. https://doi.org/10.3748/wjg.v22.i30.6944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Strickler JH, Wu C, Bekaii-Saab T. Targeting BRAF in metastatic colorectal cancer: maximizing molecular approaches. Cancer Treat Rev. 2017;60:109–19. https://doi.org/10.1016/j.ctrv.2017.08.006.

    Article  CAS  PubMed  Google Scholar 

  32. Verma S, Joy AA, Rayson D, McLeod D, Brezden-Masley C, Boileau JF, et al. HER story: the next chapter in HER-2-directed therapy for advanced breast cancer. Oncologist. 2013;18(11):1153–66. https://doi.org/10.1634/theoncologist.2013-0217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Baselga J, Coleman RE, Cortés J, Janni W. Advances in the management of HER2-positive early breast cancer. Crit Rev Oncol Hematol. 2017;119:113–22. https://doi.org/10.1016/j.critrevonc.2017.10.001.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ménard S, Pupa SM, Campiglio M, Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene. 2003;22(42):6570–8. https://doi.org/10.1038/sj.onc.1206779.

    Article  CAS  PubMed  Google Scholar 

  35. Ben-Baruch NE, Bose R, Kavuri SM, Ma CX, Ellis MJ. HER2-mutated breast cancer responds to treatment with single-agent neratinib, a second-generation HER2/EGFR tyrosine kinase inhibitor. J Natl Compr Cancer Netw. 2015;13(9):1061–4. https://doi.org/10.6004/jnccn.2015.0131.

    Article  CAS  Google Scholar 

  36. Wesoła M, Jeleń M. A comparison of IHC and FISH cytogenetic methods in the evaluation of HER2 status in breast cancer. Adv Clin Exp Med. 2015;24(5):899–904. https://doi.org/10.17219/acem/27923.

    Article  PubMed  Google Scholar 

  37. Pulford K, Morris SW, Turturro F. Anaplastic lymphoma kinase proteins in growth control and cancer. J Cell Physiol. 2004;199(3):330–58. https://doi.org/10.1002/jcp.10472.

    Article  CAS  PubMed  Google Scholar 

  38. Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature. 2007;448(7153):561–6. https://doi.org/10.1038/nature05945.

    Article  CAS  PubMed  Google Scholar 

  39. Shaw AT, Kim D-W, Nakagawa K, Seto T, Crinó L, Ahn M-J, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385–94. https://doi.org/10.1056/NEJMoa1214886.

    Article  CAS  PubMed  Google Scholar 

  40. Yoshimura Y, Kurasawa M, Yorozu K, Puig O, Bordogna W, Harada N. Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation. Cancer Chemother Pharmacol. 2016;77(3):623–8. https://doi.org/10.1007/s00280-016-2977-y.

    Article  CAS  PubMed  Google Scholar 

  41. Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129–39. https://doi.org/10.1056/NEJMoa040938.

    Article  CAS  PubMed  Google Scholar 

  42. Gristina V, Malapelle U, Galvano A, Pisapia P, Pepe F, Rolfo C, et al. The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: a systematic review and critical appraisal. Cancer Treat Rev. 2020;85:101994. https://doi.org/10.1016/j.ctrv.2020.101994.

    Article  CAS  PubMed  Google Scholar 

  43. Lee CK, Wu Y-L, Ding PN, Lord SJ, Inoue A, Zhou C, et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol. 2015;33(17):1958–65. https://doi.org/10.1200/jco.2014.58.1736.

    Article  CAS  PubMed  Google Scholar 

  44. Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, et al. Osimertinib or platinum–pemetrexed in EGFR T790M–positive lung cancer. N Engl J Med. 2017;376(7):629–40. https://doi.org/10.1056/NEJMoa1612674.

    Article  CAS  PubMed  Google Scholar 

  45. Badalamenti G, Fanale D, Incorvaia L, Barraco N, Listì A, Maragliano R, et al. Role of tumor-infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone? Cell Immunol. 2019;343:103753. https://doi.org/10.1016/j.cellimm.2018.01.013.

    Article  CAS  PubMed  Google Scholar 

  46. Incorvaia L, Badalamenti G, Rinaldi G, Iovanna JL, Olive D, Swayden M, et al. Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma? Ther Adv Med Oncol. 2019;11:175883591984887. https://doi.org/10.1177/1758835919848872.

    Article  CAS  Google Scholar 

  47. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54. https://doi.org/10.1056/NEJMoa1200690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Schreiber RD, Old LJ, Smyth MJ. Cancer Immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70. https://doi.org/10.1126/science.1203486.

    Article  CAS  PubMed  Google Scholar 

  49. Incorvaia L, Fanale D, Badalamenti G, Barraco N, Bono M, Corsini LR, et al. Programmed Death Ligand 1 (PD-L1) as a predictive biomarker for pembrolizumab therapy in patients with advanced Non-Small-Cell Lung cancer (NSCLC). Adv Ther. 2019;36(10):2600–17. https://doi.org/10.1007/s12325-019-01057-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Corsini LR, Fanale D, Passiglia F, Incorvaia L, Gennusa V, Bazan V, et al. Monoclonal antibodies for the treatment of non-hematological tumors: a safety review. Expert Opin Drug Saf. 2018;17(12):1197–209. https://doi.org/10.1080/14740338.2018.1550068.

    Article  CAS  PubMed  Google Scholar 

  51. Simanshu DK, Nissley DV, McCormick F. RAS proteins and their regulators in human disease. Cell. 2017;170(1):17–33. https://doi.org/10.1016/j.cell.2017.06.009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hobbs GA, Der CJ, Rossman KL. RAS isoforms and mutations in cancer at a glance. J Cell Sci. 2016;129(7):1287–92. https://doi.org/10.1242/jcs.182873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Rizzo S, Bronte G, Fanale D, Corsini L, Silvestris N, Santini D, et al. Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy? Cancer Treat Rev. 2010;36:S56–61. https://doi.org/10.1016/s0305-7372(10)70021-9.

    Article  CAS  PubMed  Google Scholar 

  54. Bronte G, Silvestris N, Castiglia M, Galvano A, Passiglia F, Sortino G, et al. New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: do all roads lead to RAS? Oncotarget. 2015;6(28):24780–96. https://doi.org/10.18632/oncotarget.4959.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lindsay CR, Blackhall FH. Direct Ras G12C inhibitors: crossing the rubicon. Br J Cancer. 2019;121(3):197–8. https://doi.org/10.1038/s41416-019-0499-1.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Galvano A, Taverna S, Badalamenti G, et al. Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis. Ther Adv Med Oncol. 2019;11:1758835919874653. Published 2019 Sep 10. https://doi.org/10.1177/1758835919874653.

  57. Garzón M, Villatoro S, Teixidó C, Mayo C, Martínez A, de los Llanos Gil M, et al. KRAS mutations in the circulating free DNA (cfDNA) of non-small cell lung cancer (NSCLC) patients. Transl Lung Cancer Res. 2016;5(5):511–6. https://doi.org/10.21037/tlcr.2016.10.14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Braig F, Voigtlaender M, Schieferdecker A, Busch C-J, Laban S, Grob T, et al. Liquid biopsy monitoring uncovers acquired RAS-mediated resistance to cetuximab in a substantial proportion of patients with head and neck squamous cell carcinoma. Oncotarget. 2016;7(28):42988–95. https://doi.org/10.18632/oncotarget.8943.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Fedorenko IV, Wargo JA, Flaherty KT, Messina JL, Smalley KSM. BRAF inhibition generates a host–tumor niche that mediates therapeutic escape. J Investig Dermatol. 2015;135(12):3115–24. https://doi.org/10.1038/jid.2015.329.

    Article  CAS  PubMed  Google Scholar 

  60. Pracht M, Mogha A, Lespagnol A, Fautrel A, Mouchet N, Le Gall F, et al. Prognostic and predictive values of oncogenicBRAF, NRAS, c-KITandMITFin cutaneous and mucous melanoma. J Eur Acad Dermatol Venereol. 2015;29(8):1530–8. https://doi.org/10.1111/jdv.12910.

    Article  CAS  PubMed  Google Scholar 

  61. Obaid N, Bedard K, Huang W-Y. Strategies for overcoming resistance in tumours harboring BRAF mutations. Int J Mol Sci. 2017;18(3):585. https://doi.org/10.3390/ijms18030585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Fedorenko IV, Paraiso KHT, Smalley KSM. Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma. Biochem Pharmacol. 2011;82(3):201–9. https://doi.org/10.1016/j.bcp.2011.05.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, et al. Survival in BRAF V600–mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012;366(8):707–14. https://doi.org/10.1056/NEJMoa1112302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Griffin M, Scotto D, Josephs DH, Mele S, Crescioli S, Bax HJ, et al. BRAF inhibitors: resistance and the promise of combination treatments for melanoma. Oncotarget. 2017;8(44):78174–92. https://doi.org/10.18632/oncotarget.19836.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland Å, et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18(10):1307–16. https://doi.org/10.1016/s1470-2045(17)30679-4.

    Article  CAS  PubMed  Google Scholar 

  66. Boku N. HER2-positive gastric cancer. Gastric Cancer. 2013;17(1):1–12. https://doi.org/10.1007/s10120-013-0252-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Galanti D, Inno A, La Vecchia M, et al. Current treatment options for HER2-positive breast cancer patients with brain metastases. Crit Rev Oncol Hematol. 2021;161:103329. https://doi.org/10.1016/j.critrevonc.2021.103329.

  68. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91. https://doi.org/10.1056/NEJMoa1209124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015;372(2):134–41. https://doi.org/10.1056/NEJMoa1406281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bang Y-J, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97. https://doi.org/10.1016/s0140-6736(10)61121-x.

    Article  CAS  PubMed  Google Scholar 

  71. Kivilcim Uprak T, Attaallah W, Ataizi Celikel C, Ayranci G, Yegen C. HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. Turkish J Surg. 2015;31(4):207–13. https://doi.org/10.5152/ucd.2015.2964.

    Article  Google Scholar 

  72. Zarogoulidis P, Spanoudakis M, Karanikas M, Courcoutsakis N, Machairiotis N, Mitrakas A, et al. Non-Hodgkin lymphoma and GIST: molecular pathways and clinical expressions. Onco Targets Therapy. 2012;5:433. https://doi.org/10.2147/ott.s38645.

    Article  Google Scholar 

  73. Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem. 2004;279(30):31655–63. https://doi.org/10.1074/jbc.M403319200.

    Article  CAS  PubMed  Google Scholar 

  74. del Cerro M, Ison JR, Bowen GP, Lazar E, del Cerro C. Intraretinal grafting restores visual function in light-blinded rats. Neuroreport. 1991;2(9):529–32. https://doi.org/10.1097/00001756-199109000-00008.

  75. Wakai T, Kanda T, Hirota S, Ohashi A, Shirai Y, Hatakeyama K. Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation. Br J Cancer. 2004;90(11):2059–61. https://doi.org/10.1038/sj.bjc.6601819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Incorvaia L, Fanale D, Vincenzi B, et al. Type and gene location of kit mutations predict progression-free survival to first-line imatinib in gastrointestinal stromal tumors: a look into the exon. Cancers (Basel). 2021;13(5):993. Published 2021 Feb 27. https://doi.org/10.3390/cancers13050993.

  77. Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007;131(6):1190–203. https://doi.org/10.1016/j.cell.2007.11.025.

    Article  CAS  PubMed  Google Scholar 

  78. Davies KD, Doebele RC. Molecular pathways: ROS1 fusion proteins in cancer. Clin Cancer Res. 2013;19(15):4040–5. https://doi.org/10.1158/1078-0432.ccr-12-2851.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bergethon K, Shaw AT, Ignatius Ou S-H, Katayama R, Lovly CM, McDonald NT, et al. ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8):863–70. https://doi.org/10.1200/jco.2011.35.6345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shimokawa M, Nosaki K, Seto T, Ohashi K, Morise M, Horinouchi H, et al. Phase II, open-label, multicenter trial of crizotinib in Japanese patients with advanced non-small cell lung cancer harboring a MET gene alteration: Co-MET study. Trials. 2020;21(1):298. https://doi.org/10.1186/s13063-020-4221-7.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Garrido P, Conde E, de Castro J, Gómez-Román JJ, Felip E, Pijuan L et al. Updated guidelines for predictive biomarker testing in advanced non-small-cell lung cancer: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology. Clin Transl Oncol. 2019. https://doi.org/10.1007/s12094-019-02218-4.

  82. Awad MM, Oxnard GR, Jackman DM, Savukoski DO, Hall D, Shivdasani P, et al. MET Exon 14 mutations in non–small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression. J Clin Oncol. 2016;34(7):721–30. https://doi.org/10.1200/jco.2015.63.4600.

    Article  CAS  PubMed  Google Scholar 

  83. Sabari JK, Santini F, Bergagnini I, Lai WV, Arbour KC, Drilon A. Changing the therapeutic landscape in non-small cell lung cancers: the evolution of comprehensive molecular profiling improves access to therapy. Curr Oncol Rep. 2017;19(4):24. https://doi.org/10.1007/s11912-017-0587-4.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Farago AF, Taylor MS, Doebele RC, Zhu VW, Kummar S, Spira AI, et al. Clinicopathologic features of non–small-cell lung cancer harboring an NTRK gene fusion. JCO Precis Oncol. 2018;2:1–12. https://doi.org/10.1200/po.18.00037.

    Article  Google Scholar 

  85. Wong DD, Vargas AC, Bonar F, Maclean F, Kattampallil J, Stewart C, et al. NTRK-rearranged mesenchymal tumours: diagnostic challenges, morphological patterns and proposed testing algorithm. Pathology. 2020;52(4):401–9. https://doi.org/10.1016/j.pathol.2020.02.004.

    Article  CAS  PubMed  Google Scholar 

  86. Penault-Llorca F, Rudzinski ER, Sepulveda AR. Testing algorithm for identification of patients with TRK fusion cancer. J Clin Pathol. 2019;72(7):460–7. https://doi.org/10.1136/jclinpath-2018-205679.

    Article  CAS  PubMed  Google Scholar 

  87. Laetsch TW, Hawkins DS. Larotrectinib for the treatment of TRK fusion solid tumors. Expert Rev Anticancer Ther. 2018;19(1):1–10. https://doi.org/10.1080/14737140.2019.1538796.

    Article  CAS  PubMed  Google Scholar 

  88. Al-Salama ZT, Keam SJ. Entrectinib: first global approval. Drugs. 2019;79(13):1477–83. https://doi.org/10.1007/s40265-019-01177-y.

    Article  PubMed  Google Scholar 

  89. Russo A, Incorvaia L, Malapelle U, et al. The tumor-agnostic treatment for patients with solid tumors: a position paper on behalf of the AIOM-SIAPEC/IAP-SIBIOC-SIF italian scientific societies [published online ahead of print, 2021 Aug 6]. Crit Rev Oncol Hematol. 2021;103436. https://doi.org/10.1016/j.critrevonc.2021.103436.

  90. Li AY, McCusker MG, Russo A, Scilla KA, Gittens A, Arensmeyer K, et al. RET fusions in solid tumors. Cancer Treat Rev. 2019;81:101911. https://doi.org/10.1016/j.ctrv.2019.101911.

    Article  CAS  PubMed  Google Scholar 

  91. Gainor JF, Lee DH, Curigliano G, Doebele RC, Kim D-W, Baik CS, et al. Clinical activity and tolerability of BLU-667, a highly potent and selective RET inhibitor, in patients (pts) with advanced RET-fusion+ non-small cell lung cancer (NSCLC). J Clin Oncol. 2019;37(15_suppl):9008. https://doi.org/10.1200/JCO.2019.37.15_suppl.9008.

    Article  Google Scholar 

  92. Büttner R, Longshore JW, López-Ríos F, Merkelbach-Bruse S, Normanno N, Rouleau E, et al. Implementing TMB measurement in clinical practice: considerations on assay requirements. ESMO Open. 2019;4(1):e000442. https://doi.org/10.1136/esmoopen-2018-000442.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Chan TA, Yarchoan M, Jaffee E, Swanton C, Quezada SA, Stenzinger A, et al. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol. 2019;30(1):44–56. https://doi.org/10.1093/annonc/mdy495.

    Article  CAS  PubMed  Google Scholar 

  94. Nie W, Qian J, Xu M-D, Gu K, Qian F-F, Hu M-J, et al. A non-linear association between blood tumor mutation burden and prognosis in NSCLC patients receiving atezolizumab. OncoImmunology. 2020;9(1):1731072. https://doi.org/10.1080/2162402x.2020.1731072.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Samstein RM, Lee C-H, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51(2):202–6. https://doi.org/10.1038/s41588-018-0312-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Dunn BK, Akpa E. Biomarkers as surrogate endpoints in cancer trials. Semin Oncol Nurs. 2012;28(2):99–108. https://doi.org/10.1016/j.soncn.2012.03.006.

    Article  PubMed  Google Scholar 

  97. Katz R. Biomarkers and surrogate markers: an FDA perspective. NeuroRx. 2004;1(2):189–95. https://doi.org/10.1602/neurorx.1.2.189.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Fleming TR, Powers JH. Biomarkers and surrogate endpoints in clinical trials. Stat Med. 2012;31(25):2973–84. https://doi.org/10.1002/sim.5403.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Taioli E. Biomarkers of genetic susceptibility to cancer: applications to epidemiological studies. Future Oncol. 2005;1(1):51–6. https://doi.org/10.1517/14796694.1.1.51.

    Article  CAS  PubMed  Google Scholar 

  100. Incorvaia L, Passiglia F, Rizzo S, et al. “Back to a false normality”: new intriguing mechanisms of resistance to PARP inhibitors. Oncotarget. 2017;8(14):23891–904. https://doi.org/10.18632/oncotarget.14409.

  101. Incorvaia L, Fanale D, Bono M, et al. BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype-phenotype correlation in a cohort of 531 patients. Ther Adv Med Oncol. 2020;12:1758835920975326. Published 2020 Dec 16. https://doi.org/10.1177/1758835920975326.

  102. Fanale D, Incorvaia L, Filorizzo C, et al. Detection of germline mutations in a cohort of 139 patients with bilateral breast cancer by multi-gene panel testing: impact of pathogenic variants in other genes beyond BRCA1/2. Cancers (Basel). 2020;12(9):2415. Published 2020 Aug 25. https://doi.org/10.3390/cancers12092415.

  103. Cohen-Haguenauer O. Prédisposition héréditaire au cancer du sein (1). Méd Sci. 2019;35(2):138–51. https://doi.org/10.1051/medsci/2019003.

    Article  Google Scholar 

  104. Russo A, Calò V, Bruno L, Schirò V, Agnese V, Cascio S, et al. Is BRCA1-5083del19, identified in breast cancer patients of Sicilian origin, a Calabrian founder mutation? Breast Cancer Res Treat. 2008;113(1):67–70. https://doi.org/10.1007/s10549-008-9906-7.

    Article  CAS  PubMed  Google Scholar 

  105. Incorvaia L, Fanale D, Badalamenti G, Bono M, Calò V, Cancelliere D, et al. Hereditary breast and ovarian cancer in families from southern Italy (Sicily)—prevalence and geographic distribution of pathogenic variants in BRCA1/2 genes. Cancers. 2020;12(5):1158. https://doi.org/10.3390/cancers12051158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gori S, Barberis M, Bella MA, Buttitta F, Capoluongo E, Carrera P, et al. Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives. Crit Rev Oncol Hematol. 2019;140:67–72. https://doi.org/10.1016/j.critrevonc.2019.05.012.

    Article  PubMed  Google Scholar 

  107. Bono M, Fanale D, Incorvaia L, et al. Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge [published online ahead of print, 2021 Aug 6]. ESMO Open. 2021;6(4):100235. https://doi.org/10.1016/j.esmoop.2021.100235.

  108. Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. 2010;138(6):2044–58. https://doi.org/10.1053/j.gastro.2010.01.054.

    Article  CAS  PubMed  Google Scholar 

  109. Cicek MS, Lindor NM, Gallinger S, Bapat B, Hopper JL, Jenkins MA, et al. Quality assessment and correlation of microsatellite instability and immunohistochemical markers among population- and clinic-based colorectal tumors. J Mol Diagn. 2011;13(3):271–81. https://doi.org/10.1016/j.jmoldx.2010.12.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Richman S. Deficient mismatch repair: read all about it (review). Int J Oncol. 2015;47(4):1189–202. https://doi.org/10.3892/ijo.2015.3119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Dudley JC, Lin MT, Le DT, Eshleman JR. Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res. 2016;22(4):813–20. https://doi.org/10.1158/1078-0432.ccr-15-1678.

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. Fiorella Guadagni, Sofia Cutaia and Giorgio Madonia should be considered equally co-first authors.

  2. Viviana Bazan and Paolo Vigneri should be considered equally co-last authors.

Authors and Affiliations

  1. Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, Rome, Italy

    Fiorella Guadagni

  2. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Giorgio Madonia

  3. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Valerio Gristina

  4. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Sofia Cutaia & Lidia Rita Corsini

  5. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy

    Lorena Incorvaia

  6. Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University of Palermo, Palermo, Italy

    Viviana Bazan

  7. Center of Experimental Oncology and Hematology, A.O.U. Policlinico “G. Rodolico - S. Marco”, Catania, Italy

    Claudio Longhitano, Federica Martorana & Paolo Vigneri

  8. Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université et Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France

    Juan Lucio Iovanna

  9. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Daniele Fanale

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  1. Fiorella Guadagni
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Editors and Affiliations

  1. Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

    Antonio Russo

  2. Oncology Department, University of Antwerp, Edegem, Belgium

    Marc Peeters

  3. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy

    Lorena Incorvaia

  4. Center for Thoracic Oncology, Tisch Cancer Institute, Mount Sinai System & Icahn School of Medicine, Mount Sinai, NY, USA

    Christian Rolfo

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Guadagni, F. et al. (2021). Biomarkers. In: Russo, A., Peeters, M., Incorvaia, L., Rolfo, C. (eds) Practical Medical Oncology Textbook. UNIPA Springer Series. Springer, Cham. https://doi.org/10.1007/978-3-030-56051-5_4

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