Skip to main content

Advertisement

SpringerLink
Log in

Genetics of rectal cancer and novel therapies: primer for radiologists

  • Special Section: Rectal Cancer
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Rectal cancer accounts for one-third of newly diagnosed colorectal cancer cases. Given its anatomical location and risk for local recurrence, a multidisciplinary treatment program including surgery, radiation therapy, and chemotherapy has demonstrated improved outcomes in localized disease. Genetic analysis has become part of the standard approach for management of advanced disease and new trials are considering tailored therapies for locally advanced disease. This review describes molecular subsets of colorectal cancer; implications for clinical management, including patterns of metastatic spread and response to therapies; and emerging matched therapies. During the last decade, significant biological differences have been noted based on colorectal cancer primary location and here we focus on rectal cancers and relevant markers for this disease. As more treatment for localized rectal cancer is shifted to the neoadjuvant setting and more targeted regimens are developed for metastatic disease, radiologists will increasingly see patients defined by molecular subsets and their awareness of the genetics of rectal cancer will help further refine our understanding of this disease.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2017) Cancer Statistics, 2017. CA Cancer J Clin 67 (1):7-30. doi:https://doi.org/10.3322/caac.21387

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Fedewa SA, Ahnen DJ, Meester RGS, Barzi A, Jemal A (2017) Colorectal cancer statistics, 2017. CA Cancer J Clin 67 (3):177-193. doi:https://doi.org/10.3322/caac.21395

    Article  PubMed  Google Scholar 

  3. Markowitz SD, Bertagnolli MM (2009) Molecular origins of cancer: Molecular basis of colorectal cancer. N Engl J Med 361 (25):2449-2460. doi:https://doi.org/10.1056/NEJMra0804588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61 (5):759-767

    Article  CAS  PubMed  Google Scholar 

  5. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144 (5):646-674. doi:https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  6. Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396 (6712):643-649. doi:https://doi.org/10.1038/25292

    Article  CAS  PubMed  Google Scholar 

  7. Pino MS, Chung DC (2010) The chromosomal instability pathway in colon cancer. Gastroenterology 138 (6):2059-2072. doi:https://doi.org/10.1053/j.gastro.2009.12.065

    Article  CAS  PubMed  Google Scholar 

  8. Perea J, Rueda D, Canal A, Rodriguez Y, Alvaro E, Osorio I, Alegre C, Rivera B, Martinez J, Benitez J, Urioste M (2014) Age at onset should be a major criterion for subclassification of colorectal cancer. J Mol Diagn 16 (1):116-126. doi:https://doi.org/10.1016/j.jmoldx.2013.07.010

    Article  CAS  PubMed  Google Scholar 

  9. Fearon ER (2011) Molecular genetics of colorectal cancer. Annu Rev Pathol 6:479-507. https://doi.org/10.1146/annurev-pathol-011110-130235

    Article  CAS  PubMed  Google Scholar 

  10. Vilar E, Tabernero J (2013) Molecular dissection of microsatellite instable colorectal cancer. Cancer Discov 3 (5):502-511. https://doi.org/10.1158/2159-8290.CD-12-0471

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gavin PG, Colangelo LH, Fumagalli D, Tanaka N, Remillard MY, Yothers G, Kim C, Taniyama Y, Kim SI, Choi HJ, Blackmon NL, Lipchik C, Petrelli NJ, O'Connell MJ, Wolmark N, Paik S, Pogue-Geile KL (2012) Mutation profiling and microsatellite instability in stage II and III colon cancer: an assessment of their prognostic and oxaliplatin predictive value. Clin Cancer Res 18 (23):6531-6541. doi:https://doi.org/10.1158/1078-0432.CCR-12-0605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Koopman M, Kortman GA, Mekenkamp L, Ligtenberg MJ, Hoogerbrugge N, Antonini NF, Punt CJ, van Krieken JH (2009) Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer 100 (2):266-273. doi:https://doi.org/10.1038/sj.bjc.6604867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Sato K, Kawazu M, Yamamoto Y, Ueno T, Kojima S, Nagae G, Abe H, Soda M, Oga T, Kohsaka S, Sai E, Yamashita Y, Iinuma H, Fukayama M, Aburatani H, Watanabe T, Mano H (2018) Fusion Kinases Identified by Genomic Analyses of Sporadic Microsatellite Instability-High Colorectal Cancers. Clin Cancer Res. doi:https://doi.org/10.1158/1078-0432.ccr-18-1574

  14. Issa JP (2004) CpG island methylator phenotype in cancer. Nat Rev Cancer 4 (12):988-993. doi:https://doi.org/10.1038/nrc1507

    Article  CAS  PubMed  Google Scholar 

  15. Sugai T, Habano W, Jiao YF, Tsukahara M, Takeda Y, Otsuka K, Nakamura S (2006) Analysis of molecular alterations in left- and right-sided colorectal carcinomas reveals distinct pathways of carcinogenesis: proposal for new molecular profile of colorectal carcinomas. J Mol Diagn 8 (2):193-201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. de Rosa N, Rodriguez-Bigas MA, Chang GJ, Veerapong J, Borras E, Krishnan S, Bednarski B, Messick CA, Skibber JM, Feig BW, Lynch PM, Vilar E, You YN (2016) DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics. J Clin Oncol 34 (25):3039-3046. doi:https://doi.org/10.1200/JCO.2016.66.6826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shin JS, Tut TG, Yang T, Lee CS (2013) Radiotherapy response in microsatellite instability related rectal cancer. Korean J Pathol 47 (1):1-8. doi:https://doi.org/10.4132/koreanjpathol.2013.47.1.1

    Article  PubMed  PubMed Central  Google Scholar 

  18. Franchitto A, Pichierri P, Piergentili R, Crescenzi M, Bignami M, Palitti F (2003) The mammalian mismatch repair protein MSH2 is required for correct MRE11 and RAD51 relocalization and for efficient cell cycle arrest induced by ionizing radiation in G2 phase. Oncogene 22 (14):2110-2120. doi:https://doi.org/10.1038/sj.onc.1206254

    Article  CAS  PubMed  Google Scholar 

  19. Barwell J, Pangon L, Hodgson S, Georgiou A, Kesterton I, Slade T, Taylor M, Payne SJ, Brinkman H, Smythe J, Sebire NJ, Solomon E, Docherty Z, Camplejohn R, Homfray T, Morris JR (2007) Biallelic mutation of MSH2 in primary human cells is associated with sensitivity to irradiation and altered RAD51 foci kinetics. J Med Genet 44 (8):516-520. doi:https://doi.org/10.1136/jmg.2006.048660

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hasan S, Renz P, Wegner RE, Finley G, Raj M, Monga D, McCormick J, Kirichenko A (2018) Microsatellite Instability (MSI) as an Independent Predictor of Pathologic Complete Response (PCR) in Locally Advanced Rectal Cancer: A National Cancer Database (NCDB) Analysis. Ann Surg. doi:https://doi.org/10.1097/sla.0000000000003051

  21. Cercek A, Fernandez GDS, Roxburgh C, Ng S, Yaeger R, Segal N, Ganesh K, Reidy D, Smith J, Nash G, Guillem J, Paty P, Shia J, Garcia-Aguilar J, Diaz L, Crane C, Goodman K, Saltz L, Weiser M, Stadler Z Mismatch repair deficient rectal cancer is resistant to induction combination chemotherapy. Paper presented at the 2018 ESMO Congress 29 (suppl_8): viii150-viii204.

  22. Turajlic S, Litchfield K, Xu H, Rosenthal R, McGranahan N, Reading JL, Wong YNS, Rowan A, Kanu N, Al Bakir M, Chambers T, Salgado R, Savas P, Loi S, Birkbak NJ, Sansregret L, Gore M, Larkin J, Quezada SA, Swanton C (2017) Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. Lancet Oncol 18 (8):1009-1021. doi:https://doi.org/10.1016/S1470-2045(17)30516-8

    Article  CAS  PubMed  Google Scholar 

  23. Guinney J, Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21 (11):1350-1356. doi:https://doi.org/10.1038/nm.3967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kim SR, Song N, Yothers G, Gavin PG, Allegra CJ, Paik S, Pogue-Geile KL (2018) Tumour sidedness and intrinsic subtypes in patients with stage II/III colon cancer: analysis of NSABP C-07 (NRG Oncology). Br J Cancer 118 (5):629-633. doi:https://doi.org/10.1038/bjc.2017.448

    Article  PubMed  Google Scholar 

  25. Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487 (7407):330-337. doi:https://doi.org/10.1038/nature11252

    Article  CAS  Google Scholar 

  26. Yaeger R, Chatila WK, Lipsyc MD, Hechtman JF, Cercek A, Sanchez-Vega F, Jayakumaran G, Middha S, Zehir A, Donoghue MTA, You D, Viale A, Kemeny N, Segal NH, Stadler ZK, Varghese AM, Kundra R, Gao J, Syed A, Hyman DM, Vakiani E, Rosen N, Taylor BS, Ladanyi M, Berger MF, Solit DB, Shia J, Saltz L, Schultz N (2018) Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer. Cancer Cell 33 (1):125-136.e123. doi:https://doi.org/10.1016/j.ccell.2017.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Heald RJ, Husband EM, Ryall RD (1982) The mesorectum in rectal cancer surgery--the clue to pelvic recurrence? Br J Surg 69 (10):613-616

    Article  CAS  PubMed  Google Scholar 

  28. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R, German Rectal Cancer Study G (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351 (17):1731-1740. doi:https://doi.org/10.1056/NEJMoa040694

    Article  Google Scholar 

  29. Petersen SH, Harling H, Kirkeby LT, Wille-Jørgensen P, Mocellin S (2012) Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev 3:CD004078. doi:https://doi.org/10.1002/14651858.cd004078.pub2

  30. Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol 27 (31):5124-5130. doi:https://doi.org/10.1200/JCO.2009.22.0467

    Article  PubMed  PubMed Central  Google Scholar 

  31. Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, Allen PK, Lynch PM, Glober G, Wolff R, Rich TA, Skibber J (1999) Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 44 (5):1027-1038

  32. Cercek A, Roxburgh CSD, Strombom P, Smith JJ, Temple LKF, Nash GM, Guillem JG, Paty PB, Yaeger R, Stadler ZK, Seier K, Gonen M, Segal NH, Reidy DL, Varghese A, Shia J, Vakiani E, Wu AJ, Crane CH, Gollub MJ, Garcia-Aguilar J, Saltz LB, Weiser MR (2018) Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer. JAMA Oncol 4 (6):e180071. doi:https://doi.org/10.1001/jamaoncol.2018.0071

    Article  PubMed  PubMed Central  Google Scholar 

  33. Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K, Consortium ToRCRtC (2015) Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol 16 (8):957-966. doi:https://doi.org/10.1016/S1470-2045(15)00004-2

    Article  CAS  Google Scholar 

  34. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U, Jr., Silva e Sousa AH, Jr., Campos FG, Kiss DR, Gama-Rodrigues J (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 240 (4):711-717; discussion 717-718

  35. Maas M, Beets-Tan RG, Lambregts DM, Lammering G, Nelemans PJ, Engelen SM, van Dam RM, Jansen RL, Sosef M, Leijtens JW, Hulsewe KW, Buijsen J, Beets GL (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29 (35):4633-4640. doi:https://doi.org/10.1200/JCO.2011.37.7176

    Article  PubMed  Google Scholar 

  36. Chalabi M, Fanchi L, Berg JVd, Beets G, Lopez-Yurda M, Aalbers A, Grootscholten C, PSnaebjornsson, Maas M, Mertz M, Nuijten E, Kuiper M, Kok M, Leerdam MV, Schumacher T, Voest E, Haanen J Neoadjuvant ipilimumab plus nivolumab in early stage colon cancer. Paper presented at the 2018 ESMO Congress. Abstract LBA37_PR.

  37. Ryan JE, Warrier SK, Lynch AC, Ramsay RG, Phillips WA, Heriot AG (2016) Predicting pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer: a systematic review. Colorectal Dis 18 (3):234-246. doi:https://doi.org/10.1111/codi.13207

    Article  CAS  PubMed  Google Scholar 

  38. Chow OS, Kuk D, Keskin M, Smith JJ, Camacho N, Pelossof R, Chen CT, Chen Z, Avila K, Weiser MR, Berger MF, Patil S, Bergsland E, Garcia-Aguilar J (2016) KRAS and Combined KRAS/TP53 Mutations in Locally Advanced Rectal Cancer are Independently Associated with Decreased Response to Neoadjuvant Therapy. Ann Surg Oncol 23 (8):2548-2555. doi:https://doi.org/10.1245/s10434-016-5205-4

    Article  PubMed  PubMed Central  Google Scholar 

  39. Sideris M, Moorhead J, Diaz-Cano S, Bjarnason I, Haji A, Papagrigoriadis S (2016) KRAS Mutant Status, p16 and beta-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer. Anticancer Res 36 (10):5315-5324. doi:https://doi.org/10.21873/anticanres.11104

    Article  CAS  PubMed  Google Scholar 

  40. Chiang JM, Hsieh PS, Chen JS, Tang R, You JF, Yeh CY (2014) Rectal cancer level significantly affects rates and patterns of distant metastases among rectal cancer patients post curative-intent surgery without neoadjuvant therapy. World J Surg Oncol 12:197. doi:https://doi.org/10.1186/1477-7819-12-197

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yaeger R, Cowell E, Chou JF, Gewirtz AN, Borsu L, Vakiani E, Solit DB, Rosen N, Capanu M, Ladanyi M, Kemeny N (2015) RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer. Cancer 121 (8):1195-1203. doi:https://doi.org/10.1002/cncr.29196

    Article  CAS  PubMed  Google Scholar 

  42. Kemeny NE, Chou JF, Capanu M, Gewirtz AN, Cercek A, Kingham TP, Jarnagin WR, Fong YC, DeMatteo RP, Allen PJ, Shia J, Ang C, Vakiani E, D'Angelica MI (2014) KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer 120 (24):3965-3971. doi:https://doi.org/10.1002/cncr.28954

    Article  CAS  PubMed  Google Scholar 

  43. Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD (2013) Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369 (11):1023-1034. doi:https://doi.org/10.1056/NEJMoa1305275

    Article  CAS  PubMed  Google Scholar 

  44. Cercek A, Braghiroli MI, Chou JF, Hechtman JF, Kemeny N, Saltz L, Capanu M, Yaeger R (2017) Clinical Features and Outcomes of Patients with Colorectal Cancers Harboring NRAS Mutations. Clin Cancer Res 23 (16):4753-4760. doi:https://doi.org/10.1158/1078-0432.CCR-17-0400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, Wong TW, Huang X, Takimoto CH, Godwin AK, Tan BR, Krishnamurthi SS, Burris HA, Poplin EA, Hidalgo M, Baselga J, Clark EA, Mauro DJ (2007) Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol 25 (22):3230-3237. doi:https://doi.org/10.1200/JCO.2006.10.5437

    Article  CAS  PubMed  Google Scholar 

  46. Dewdney A, Cunningham D, Tabernero J, Capdevila J, Glimelius B, Cervantes A, Tait D, Brown G, Wotherspoon A, Gonzalez de Castro D, Chua YJ, Wong R, Barbachano Y, Oates J, Chau I (2012) Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol 30 (14):1620-1627. doi:https://doi.org/10.1200/JCO.2011.39.6036

    Article  CAS  PubMed  Google Scholar 

  47. Merx K, Martens UM, Kripp M, Hoehler T, Geissler M, Gaiser T, Mai S, Kienle P, Belle S, Ploger C, Hieber U, Wenz F, Post S, Hofheinz RD (2017) Panitumumab in Combination With Preoperative Radiation Therapy in Patients With Locally Advanced RAS Wild-type Rectal Cancer: Results of the Multicenter Explorative Single-Arm Phase 2 Study NEORIT. Int J Radiat Oncol Biol Phys 99 (4):867-875. doi:https://doi.org/10.1016/j.ijrobp.2017.06.2460

    Article  CAS  PubMed  Google Scholar 

  48. Eisterer W, De Vries A, Ofner D, Rabl H, Koplmuller R, Greil R, Tschmelitsch J, Schmid R, Kapp K, Lukas P, Sedlmayer F, Hofler G, Gnant M, Thaler J, Austrian B, Colorectal Cancer Study G (2014) Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer--a phase II clinical trial. Anticancer Res 34 (11):6767-6773

    Google Scholar 

  49. Kim SY, Shim EK, Yeo HY, Baek JY, Hong YS, Kim DY, Kim TW, Kim JH, Im SA, Jung KH, Chang HJ (2013) KRAS mutation status and clinical outcome of preoperative chemoradiation with cetuximab in locally advanced rectal cancer: a pooled analysis of 2 phase II trials. Int J Radiat Oncol Biol Phys 85 (1):201-207. doi:https://doi.org/10.1016/j.ijrobp.2012.03.048

    Article  CAS  PubMed  Google Scholar 

  50. Horisberger K, Treschl A, Mai S, Barreto-Miranda M, Kienle P, Strobel P, Erben P, Woernle C, Dinter D, Kahler G, Hochhaus A, Post S, Willeke F, Wenz F, Hofheinz RD, Margit (2009) Cetuximab in combination with capecitabine, irinotecan, and radiotherapy for patients with locally advanced rectal cancer: results of a Phase II MARGIT trial. Int J Radiat Oncol Biol Phys 74 (5):1487-1493. doi:https://doi.org/10.1016/j.ijrobp.2008.10.014

    Article  CAS  PubMed  Google Scholar 

  51. Seo AN, Kwak Y, Kim DW, Kang SB, Choe G, Kim WH, Lee HS (2014) HER2 status in colorectal cancer: its clinical significance and the relationship between HER2 gene amplification and expression. PLoS One 9 (5):e98528. doi:https://doi.org/10.1371/journal.pone.0098528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Meng X, Huang Z, Di J, Mu D, Wang Y, Zhao X, Zhao H, Zhu W, Li X, Kong L, Xing L (2015) Expression of Human Epidermal Growth Factor Receptor-2 in Resected Rectal Cancer. Medicine (Baltimore) 94 (47):e2106. doi:https://doi.org/10.1097/MD.0000000000002106

    Article  CAS  Google Scholar 

  53. Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S, Bergamo F, Zagonel V, Leone F, Depetris I, Martinelli E, Troiani T, Ciardiello F, Racca P, Bertotti A, Siravegna G, Torri V, Amatu A, Ghezzi S, Marrapese G, Palmeri L, Valtorta E, Cassingena A, Lauricella C, Vanzulli A, Regge D, Veronese S, Comoglio PM, Bardelli A, Marsoni S, Siena S (2016) Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial. Lancet Oncol 17 (6):738-746. doi:https://doi.org/10.1016/S1470-2045(16)00150-9

    Article  CAS  PubMed  Google Scholar 

  54. Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, Burris H, Bose R, Yoo B, Stein A, Beattie M, Kurzrock R (2018) Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles: Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study. J Clin Oncol 36 (6):536-542. doi:https://doi.org/10.1200/JCO.2017.75.3780

    Article  CAS  PubMed  Google Scholar 

  55. Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F (2011) Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 29 (15):2011-2019. doi:https://doi.org/10.1200/JCO.2010.33.5091

    Article  CAS  PubMed  Google Scholar 

  56. van Brummelen EMJ, de Boer A, Beijnen JH, Schellens JHM (2017) BRAF Mutations as Predictive Biomarker for Response to Anti-EGFR Monoclonal Antibodies. Oncologist 22 (7):864-872. doi:https://doi.org/10.1634/theoncologist.2017-0031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kopetz S, McDonough SL, Morris VK, Lenz H-J, Magliocco AM, Atreya CE, Diaz LA, Allegra CJ, Wang SE, Lieu CH, Eckhardt SG, Semrad TJ, Kaberle K, Guthrie KA, Hochster HS (2017) Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406). Journal of Clinical Oncology 35 (4_suppl):520-520. doi:https://doi.org/10.1200/jco.2017.35.4_suppl.520

  58. Cutsem EV, Cuyle P-J, Huijberts S, Yaeger R, Schellens JHM, Elez E, Tabernero J, Fakih M, Montagut C, Peeters M, Desai J, Yoshino T, Ciardiello F, Wasan HS, Kopetz S, Maharry K, Christy-Bittel J, Gollerkeri A, Grothey A (2018) BEACON CRC study safety lead-in (SLI) in patients with BRAFV600E metastatic colorectal cancer (mCRC): Efficacy and tumor markers. Journal of Clinical Oncology 36 (4_suppl):627-627. doi:https://doi.org/10.1200/jco.2018.36.4_suppl.627

  59. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA, Jr. (2015) PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 372 (26):2509-2520. doi:https://doi.org/10.1056/NEJMoa1500596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Overman MJ, Lonardi S, Wong KYM, Lenz HJ, Gelsomino F, Aglietta M, Morse MA, Van Cutsem E, McDermott R, Hill A, Sawyer MB, Hendlisz A, Neyns B, Svrcek M, Moss RA, Ledeine JM, Cao ZA, Kamble S, Kopetz S, Andre T (2018) Durable Clinical Benefit With Nivolumab Plus Ipilimumab in DNA Mismatch Repair-Deficient/Microsatellite Instability-High Metastatic Colorectal Cancer. J Clin Oncol 36 (8):773-779. doi:https://doi.org/10.1200/JCO.2017.76.9901

    Article  CAS  PubMed  Google Scholar 

  61. Overman MJ, McDermott R, Leach JL, Lonardi S, Lenz HJ, Morse MA, Desai J, Hill A, Axelson M, Moss RA, Goldberg MV, Cao ZA, Ledeine JM, Maglinte GA, Kopetz S, André T (2017) Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol 18 (9):1182-1191. doi:https://doi.org/10.1016/S1470-2045(17)30422-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We acknowledge Walid Chatila and Marc Gollub for help with the figures.

Funding

Supported by the National Institutes of Health Memorial Sloan Kettering Cancer Center Core Grant (P30 CA 008748).

Author information

Authors and Affiliations

  1. Department of Medicine, Memorial Sloan Kettering Cancer Center, 300 E 66th Street, 10th Floor, New York, NY, 10065, USA

    Sebastian Mondaca & Rona Yaeger

Authors
  1. Sebastian Mondaca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rona Yaeger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rona Yaeger.

Ethics declarations

Conflicts of interest

R. Yaeger has served on an advisory board for GlaxoSmithKline and has received research funding from Array BioPharma, Genentech, GlaxoSmithKline, and Novartis.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mondaca, S., Yaeger, R. Genetics of rectal cancer and novel therapies: primer for radiologists. Abdom Radiol 44, 3743–3750 (2019). https://doi.org/10.1007/s00261-019-02051-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00261-019-02051-x

Keywords

Search

Navigation