Bringing important genetic discoveries to individuals who can benefit from them

Treatment

The class of inherited mutations we discovered and continue to research can help identify the best treatment choices for patients.

In our patient-centric studies, we seek to identify treatments that are the most effective with the fewest side effects for individuals who carry microRNA-disrupting mutations. Our first example, the KRAS-variant, has been shown to be is a powerful biomarker that can significantly predict sensitivity and resistance to specific cancer treatments, regardless of tumor type.

Specifically, knowing whether an individual carries this genetic mutation can help identify them as a responder or non-responder to therapies being used today. In addition, recent work has shown that the KRAS-variant is a strong biomarker of baseline immune status and inflammatory response. This has led us to apply this class of mutation to developing immunotherapies.

Research is ongoing to develop the best approaches for treating cancer patients with the KRAS-variant, as well as with other mutations in its class. By applying the information we have learned from this class of biomarkers, we can make a significant leap forward in personalizing cancer therapy.

Treatment of Cancer for Individuals with the KRAS-variant

The biology of the KRAS-variant, an inherited genetic mutation, affords great promise for treating cancer in the 20-25% of cancer patients who carry this biomarker.

In fact, recent research has shown that the KRAS-variant plays an important role in the body’s response to cancer therapies by affecting an individual’s immune system.

Specifically, studies have found that certain cancer medications are far more effective for KRAS-variant cancer patients, while others do not work well. Research to determine which treatments work best for KRAS-variant patients have been conducted in breast,1 ovarian,2,3 colon,4-17lung,18,19 and head and neck cancer.21-23

Learn more about links between the KRAS-Variant and specific Cancer Diagnoses.

Read findings about specific types of cancers, please review our scientific publications.

MiraKind’s research is focused on better understanding the lifestyle and environmental factors that impact cancer risk for KRAS-variant individuals so that they may make informed decisions to protect their health.

Learn more about MiraKind’s open or future research studies that may be relevant to you.

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  1. Ustinova M, Daneberga Z, Bērziņa D, Nakazawa-Miklaševiča M, Maksimenko J, Gardovskis J, Miklaševičs E. (2015). Impact of KRAS variant rs61764370 on breast cancer morbidity. Exp Oncol. 2015 Dec;37(4):292-4.
  2. Ratner ES, Keane FK, Lindner R, Tassi RA, Paranjape T, Glasgow M, Nallur S, Deng Y, Lu L, Steele L, Sand S, Muller RU, Bignotti E, Bellone S, Boeke M, Yao X, Pecorelli S, Ravaggi A, Katsaros D, Zelterman D, Cristea MC, Yu H, Rutherford TJ, Weitzel JN, Neuhausen SL, Schwartz PE, Slack FJ, Santin AD, Weidhaas JB. (2011). A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer. Oncogene. 2012 Oct 18;31(42):4559-66. doi: 10.1038/onc.2011.539. Epub 2011 Dec 5.
  3. Caiola E, Rulli E, Fruscio R, Buda A, Broggini M, Marabese M. (2012). KRAS-LCS6 polymorphism does not impact on outcomes in ovarian cancer. Am J Cancer Res. 2012;2(3):298-308. Epub 2012 Apr 21.
  4. Graziano F, Canestrari E, Loupakis F, Ruzzo A, Galluccio N, Santini D, Rocchi M, Vincenzi B, Salvatore L, Cremolini C, Spoto C, Catalano V, D’Emidio S, Giordani P, Tonini G, Falcone A, Magnani M. (2010). Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan. Pharmacogenomics J. 2010 Oct;10(5):458-64. doi: 10.1038/tpj.2010.9. Epub 2010 Feb 23.
  5. Zhang W, Winder T, Ning Y, Pohl A, Yang D, Kahn M, Lurje G, Labonte MJ, Wilson PM, Gordon MA, Hu-Lieskovan S, Mauro DJ, Langer C, Rowinsky EK, Lenz HJ. (2011). A let-7 microRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy. Ann Oncol. 2011 Jan;22(1):104-9. doi: 10.1093/annonc/mdq315. Epub 2010 Jul 5.
  6. Ruzzo A, Canestrari E, Galluccio N, Santini D, Vincenzi B, Tonini G, Magnani M, Graziano F. Role of KRAS let-7 LCS6 SNP in metastatic colorectal cancer patients. Ann Oncol. 2011 Jan;22(1):234-5. doi: 10.1093/annonc/mdq472. Epub 2010 Oct 6.
  7. Zhang W, Labonte MJ, Lenz HJ. (20111). KRAS let-7 LCS6 SNP predicts cetuximab efficacy in KRASwt metastatic colorectal cancer patients: Does treatment combination partner matter? Ann Oncol. 2011 Feb;22(2):484-5. doi: 10.1093/annonc/mdq704. Epub 2011 Jan 28.
  8. Smits KM, Paranjape T, Nallur S, Wouters KA, Weijenberg MP, Schouten LJ, van den Brandt PA, Bosman FT, Weidhaas JB, van Engeland M. (2011). A let-7 microRNA SNP in the KRAS 3’UTR is prognostic in early-stage colorectal cancer. Clin Cancer Res. 2011 Dec 15;17(24):7723-31. doi: 10.1158/1078-0432.CCR-11-0990. Epub 2011 Oct 12.
  9. Ruzzo A, Graziano F, Vincenzi B, Canestrari E, Perrone G, Galluccio N, Catalano V, Loupakis F, Rabitti C, Santini D, Tonini G, Fiorentini G, Rossi D, Falcone A, Magnani M. (2012). High let-7a microRNA levels in KRAS-mutated colorectal carcinomas may rescue anti-EGFR therapy effects in patients with chemotherapy-refractory metastatic disease. Oncologist. 2012;17(6):823-9. doi: 10.1634/theoncologist.2012-0081. Epub 2012 May 14.
  10. Ryan BM, Robles AI, Harris CC. (2012). KRAS-LCS6 genotype as a prognostic marker in early-stage CRC–letter. Clin Cancer Res. 2012 Jun 15;18(12):3487-8; author reply 3489. doi: 10.1158/1078-0432.CCR-12-0250. Epub 2012 Jun 5.
  11. Kjersem JB, Ikdahl T, Guren T, Skovlund E, Sorbye H, Hamfjord J, Pfeiffer P, Glimelius B, Kersten C, Solvang H, Tveit KM, Kure EH. (2012). Let-7 miRNA-binding site polymorphism in the KRAS 3’UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/- cetuximab. BMC Cancer. 2012 Nov 20;12:534. doi: 10.1186/1471-2407-12-534.
  12. Sebio A, Paré L, Páez D, Salazar J, González A, Sala N, del Río E, Martín-Richard M, Tobeña M, Barnadas A, Baiget M. (2013). The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3′-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients. Pharmacogenet Genomics. 2013 Mar;23(3):142-7. doi: 10.1097/FPC.0b013e32835d9b0b.
  13. Sha D, Lee AM, Shi Q, Alberts SR, Sargent DJ, Sinicrope FA, Diasio RB. (2014). Association study of the let-7 miRNA-complementary site variant in the 3′ untranslated region of the KRAS gene in stage III colon cancer (NCCTG N0147 Clinical Trial). Clin Cancer Res. 2014 Jun 15;20(12):3319-27. doi: 10.1158/1078-0432.CCR-14-0069. Epub 2014 Apr 11.
  14. Langevin SM, Christensen BC. (2014). Let-7 microRNA-binding-site polymorphism in the 3’UTR of KRAS and colorectal cancer outcome: a systematic review and meta-analysis. Cancer Med. 2014 Oct;3(5):1385-95. doi: 10.1002/cam4.279. Epub 2014 Jun 2. Review.
  15. Saridaki Z, Weidhaas JB, Lenz HJ, Laurent-Puig P, Jacobs B, De Schutter J, De Roock W, Salzman DW, Zhang W, Yang D, Pilati C, Bouché O, Piessevaux H, Tejpar S. (2014). A let-7 microRNA-binding site polymorphism in KRAS predicts improved outcome in patients with metastatic colorectal cancer treated with salvage cetuximab/panitumumab monotherapy. Clin Cancer Res. 2014 Sep 1;20(17):4499-510. doi: 10.1158/1078-0432.CCR-14-0348.
  16. Sclafani F, Chau I, Cunningham D, Peckitt C, Lampis A, Hahne JC, Braconi C, Tabernero J, Glimelius B, Cervantes A, Begum R, Gonzalez De Castro D, Hulkki Wilson S, Eltahir Z, Wotherspoon A, Tait D, Brown G, Oates J, Valeri N. (2015). Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial. Ann Oncol. 2015 Sep;26(9):1936-41. doi: 10.1093/annonc/mdv285. Epub 2015 Jul 10.
  17. Dai Q, Wei HL, Huang J, Zhou TJ, Chai L, Yang ZH. (2016). KRAS polymorphisms are associated with survival of CRC in Chinese population. Tumour Biol. 2016
  18. Nelson HH, Christensen BC, Plaza SL, Wiencke JK, Marsit CJ, Kelsey KT. (2009). KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer.
    Lung Cancer. 2010 Jul;69(1):51-3. doi: 10.1016/j.lungcan.2009.09.008. Epub 2009 Oct 24.
  19. Ganzinelli M, Rulli E, Caiola E, Garassino MC, Broggini M, Copreni E, Piva S, Longo F, Labianca R, Bareggi C, Fabbri MA, Martelli O, Fagnani D, Locatelli MC, Bertolini A, Valmadre G, Pavese I, Calcagno A, Sarobba MG, Marabese M. (2015). Role of KRAS-LCS6 polymorphism in advanced NSCLC patients treated with erlotinib or docetaxel in second line treatment (TAILOR). Sci Rep. 2015 Nov 17;5:16331. doi: 10.1038/srep16331.
  20. Christensen BC, Moyer BJ, Avissar M, Ouellet LG, Plaza SL, McClean MD, Marsit CJ, Kelsey KT. (2009). A let-7 microRNA-binding site polymorphism in the KRAS 3′ UTR is associated with reduced survival in oral cancers. Carcinogenesis. 2009 Jun;30(6):1003-7. doi: 10.1093/carcin/bgp099. Epub 2009 Apr 20.
  21. Santiago MB, DE Lima Marson FA, Secolin R, Ribeiro JD, Lima CS, Bertuzzo CS. (2014). SLC23A2-05 (rs4987219) and KRAS-LCS6 (rs61764370) polymorphisms in patients with squamous cell carcinoma of the head and neck. Oncol Lett. 2014 Jun;7(6):1803-1811. Epub 2014 Apr 3.
  22. De Ruyck K, Duprez F, Ferdinande L, Mbah C, Rios-Velazquez E, Hoebers F, Praet M, Deron P, Bonte K, Speel EJ, Libbrecht L, De Neve W, Lambin P, Thierens H. (2014). A let-7 microRNA polymorphism in the KRAS 3′-UTR is prognostic in oropharyngeal cancer. Cancer Epidemiol. 2014 Oct;38(5):591-8. doi: 10.1016/j.canep.2014.07.008. Epub 2014 Aug 12.
  23. Chung CH, Lee JW, Slebos RJ, Howard JD, Perez J, Kang H, Fertig EJ, Considine M, Gilbert J, Murphy BA, Nallur S, Paranjape T, Jordan RC, Garcia J, Burtness B, Forastiere AA, Weidhaas JB. (2014). A 3′-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2014 Nov;25(11):2230-6. doi: 10.1093/annonc/mdu367. Epub 2014 Jul 31. Erratum in: Ann Oncol. 2015 May;26(5):1038-9.