82
Views
15
CrossRef citations to date
0
Altmetric
Review

Prospects for personalized medicine with inhibitors targeting the RAS and PI3K pathways

Pages 75-87 | Published online: 09 Jan 2014

References

  • Cox AD, Der CJ. Ras family signaling: therapeutic targeting. Cancer Biol. Ther.1, 599–606 (2002).
  • Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov.4, 988–1004 (2005).
  • Weinstein IB. Cancer. Addiction to oncogenes – the Achilles heal of cancer. Science297, 63–64 (2002).
  • Weinstein IB, Joe A. Oncogene addiction. Cancer Res.68, 3077–3080; discussion 3080 (2008).
  • Simon R. The use of genomics in clinical trial design. Clin. Cancer Res.14, 5984–5993 (2008).
  • Chau CH, Rixe O, McLeod H, Figg WD. Validation of analytic methods for biomarkers used in drug development. Clin. Cancer Res.14, 5967–5976 (2008).
  • Vogel CL, Cobleigh MA, Tripathy D et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J. Clin. Oncol.20, 719–726 (2002).
  • Hu X, Stern HM, Ge L et al. Genetic alterations and oncogenic pathways associated with breast cancer subtypes. Mol. Cancer Res.7, 511–522 (2009).
  • Johnson PH, Esteva FJ. The use of HER2 modulation in the adjuvant setting. Curr. Oncol. Rep.9, 9–16 (2007).
  • Druker BJ, Lydon NB. Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J. Clin. Invest.105, 3–7 (2000).
  • Druker BJ. Translation of the Philadelphia chromosome into therapy for CML. Blood112, 4808–4817 (2008).
  • Sequist LV, Bell DW, Lynch TJ, Haber DA. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J. Clin. Oncol.25, 587–595 (2007).
  • Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin. Oncol.26, 60–70 (1999).
  • Pegram M, Hsu S, Lewis G et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene18, 2241–2251 (1999).
  • Druker BJ, Tamura S, Buchdunger E et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–Abl positive cells. Nat. Med.2, 561–566 (1996).
  • Bos JL. Ras oncogenes in human cancer: a review. Cancer Res.49, 4682–4689 (1989).
  • Campbell PM, Singh A, Williams FJ et al. Genetic and pharmacologic dissection of Ras effector utilization in oncogenesis. Methods Enzymol.407, 195–217 (2006).
  • Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature417, 949–954 (2002).
  • Li N, Batt D, Warmuth M. B-Raf kinase inhibitors for cancer treatment. Curr. Opin. Investig. Drugs.8, 452–456 (2007).
  • Wilhelm SM, Carter C, Tang L et al. BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res.64, 7099–7109 (2004).
  • Tsai J, Lee JT, Wang W et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl Acad. Sci. USA105, 3041–3046 (2008).
  • Hoeflich KP, Herter S, Tien J et al. Antitumor efficacy of the novel RAF inhibitor GDC-0879 is predicted by BRAFV600E mutational status and sustained extracellular signal-regulated kinase/mitogen-activated protein kinase pathway suppression. Cancer Res.69, 3042–3051 (2009).
  • Flaherty K, Puzanov I, Sosman J et al. Phase I study of PLX4032: proof of concept for V600E BRAF mutation as a therapeutic target in human cancer. J. Clin. Oncol.27, 15s (2009).
  • Solit DB, Garraway LA, Pratilas CA et al.BRAF mutation predicts sensitivity to MEK inhibition. Nature439, 358–362 (2006).
  • Ball DW, Jin N, Rosen DM et al. Selective growth inhibition in BRAF mutant thyroid cancer by the mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244. J. Clin. Endocrinol. Metab.92, 4712–4718 (2007).
  • Friday BB, Yu C, Dy GK et al.BRAF V600E disrupts AZD6244-induced abrogation of negative feedback pathways between extracellular signal-regulated kinase and Raf proteins. Cancer Res.68, 6145–6153 (2008).
  • Yeh JJ, Routh ED, Rubinas T et al. KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer. Mol. Cancer Ther.8, 834–843 (2009).
  • Dougherty MK, Muller J, Ritt DA et al. Regulation of Raf-1 by direct feedback phosphorylation. Mol. Cell.17, 215–224 (2005).
  • Hall-Jackson CA, Eyers PA, Cohen P et al. Paradoxical activation of Raf by a novel Raf inhibitor. Chem. Biol.6, 559–568 (1999).
  • Hoeflich KP, O‘Brien C, Boyd Z et al.In vivoantitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin. Cancer Res.15, 4649–4664 (2009).
  • Mirzoeva OK, Das D, Heiser LM et al. Basal subtype and MAPK/ERK kinase (MEK)-phosphoinositide 3-kinase feedback signaling determine susceptibility of breast cancer cells to MEK inhibition. Cancer Res.69, 565–572 (2009).
  • Dummer R, Robert C, Chapman P et al. AZD6244 (ARRY-142886) vs temozolomide (TMZ) in patients (pts) with advanced melanoma: an open-label, randomized, multicenter, Phase II study. J. Clin. Oncol.26, (2008).
  • Haluska FG, Tsao H, Wu H, Haluska FS, Lazar A, Goel V. Genetic alterations in signaling pathways in melanoma. Clin. Cancer Res.12, S2301–S2307 (2006).
  • Simi L, Pratesi N, Vignoli M et al. High-resolution melting analysis for rapid detection of KRAS, BRAF, and PIK3CA gene mutations in colorectal cancer. Am. J. Clin. Pathol.130, 247–253 (2008).
  • Engelman JA, Chen L, Tan X et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat. Med.14, 1351–1356 (2008).
  • Jia S, Liu Z, Zhang S et al. Essential roles of PI(3)K-p110β in cell growth, metabolism and tumorigenesis. Nature454, 776–779 (2008).
  • Yuan TL, Cantley LC. PI3K pathway alterations in cancer: variations on a theme. Oncogene27, 5497–5510 (2008).
  • Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat. Rev. Immunol.3, 317–330 (2003).
  • Sasaki T, Suzuki A, Sasaki J, Penninger JM. Phosphoinositide 3-kinases in immunity: lessons from knockout mice. J. Biochem.131, 495–501 (2002).
  • Ihle NT, Lemos R, Jr., Wipf P et al. Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance. Cancer Res.69, 143–150 (2009).
  • Torbett NE, Luna-Moran A, Knight ZA et al. A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition. Biochem J.415, 97–110 (2008).
  • Serra V, Markman B, Scaltriti M et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res.68, 8022–8030 (2008).
  • Raynaud FI, Eccles SA, Patel S et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Mol. Cancer Ther.8, 1725–1738 (2009).
  • Shayesteh L, Lu Y, Kuo WL et al. PIK3CA is implicated as an oncogene in ovarian cancer. Nat. Genet.21, 99–102 (1999).
  • Hu L, Zaloudek C, Mills GB, Gray J, Jaffe RB. In vivo and in vitro ovarian carcinoma growth inhibition by a phosphatidylinositol 3-kinase inhibitor (LY294002). Clin. Cancer Res.6, 880–886 (2000).
  • Fletcher JA, Rubin BP. KIT mutations in GIST. Curr. Opin. Genet. Dev.17, 3–7 (2007).
  • Labropoulos SV, Fletcher JA, Oliveira AM, Papadopoulos S, Razis ED. Sustained complete remission of metastatic dermatofibrosarcoma protuberans with imatinib mesylate. Anticancer Drugs16, 461–466 (2005).
  • Carpten JD, Faber AL, Horn C et al. A transforming mutation in the pleckstrin homology domain of AKT1 in cancer. Nature448, 439–444 (2007).
  • Stemke-Hale K, Gonzalez-Angulo AM, Lluch A et al. An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res.68, 6084–6091 (2008).
  • Hennessy BT, Lu Y, Poradosu E et al. Pharmacodynamic markers of perifosine efficacy. Clin. Cancer Res.13, 7421–7431 (2007).
  • She QB, Chandarlapaty S, Ye Q et al. Breast tumor cells with PI3K mutation or HER2 amplification are selectively addicted to Akt signaling. PLoS One3, e3065 (2008).
  • Tolcher AW, Yap TA, Fearen I et al. A Phase I study of MK-2206, an oral potent allosteric Akt inhibitor (Akti), in patients with advanced solid tumor. J. Clin. Oncol.27(15), 3503 (2009).
  • Fasolo A, Sessa C. mTOR inhibitors in the treatment of cancer. Expert Opin. Investig. Drugs17, 1717–1734 (2008).
  • Dasanu CA, Clark BA 3rd, Alexandrescu DT. mTOR-blocking agents in advanced renal cancer: an emerging therapeutic option. Expert Opin. Investig. Drugs18, 175–187 (2009).
  • Toschi A, Lee E, Gadir N, Ohh M, Foster DA. Differential dependence of hypoxia-inducible factors 1α and 2α on mTORC1 and mTORC2. J. Biol. Chem.283, 34495–34499 (2008).
  • Baselga J, Semiglazov V, van Dam P et al. Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J. Clin. Oncol.27, 2630–2637 (2009).
  • Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science307, 1098–1101 (2005).
  • Feldman ME, Apsel B, Uotila A et al. Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol.7, e38 (2009).
  • Guertin DA, Stevens DM, Saitoh M et al. mTOR complex 2 is required for the development of prostate cancer induced by PTEN loss in mice. Cancer Cell15, 148–159 (2009).
  • Sakatani T, Onyango P. Oncogenomics: prospects for the future. Expert Rev. Anticancer Ther.3, 891–901 (2003).
  • Bild AH, Potti A, Nevins JR. Linking oncogenic pathways with therapeutic opportunities. Nat. Rev. Cancer6, 735–741 (2006).
  • Bild AH, Yao G, Chang JT et al. Oncogenic pathway signatures in human cancers as a guide to targeted therapies. Nature439, 353–357 (2006).
  • Potti A, Dressman HK, Bild A et al. Genomic signatures to guide the use of chemotherapeutics. Nat. Med.12, 1294–1300 (2006).
  • Saal LH, Johansson P, Holm K et al. Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc. Natl Acad. Sci. USA104, 7564–7569 (2007).
  • Singh A, Greninger P, Rhodes D et al. A gene expression signature associated with “K-Ras addiction” reveals regulators of EMT and tumor cell survival. Cancer Cell15, 489–500 (2009).
  • Petricoin EF 3rd, Bichsel VE, Calvert VS et al. Mapping molecular networks using proteomics: a vision for patient-tailored combination therapy. J. Clin. Oncol.23, 3614–3621 (2005).
  • Espina V, Liotta LA, Petricoin EF 3rd. Reverse-phase protein microarrays for theranostics and patient tailored therapy. Methods Mol. Biol.520, 89–105 (2009).
  • Wulfkuhle JD, Edmiston KH, Liotta LA, Petricoin EF 3rd. Technology insight: pharmacoproteomics for cancer--promises of patient-tailored medicine using protein microarrays. Nat. Clin. Pract. Oncol.3, 256–268 (2006).
  • Wulfkuhle JD, Speer R, Pierobon M et al. Multiplexed cell signaling analysis of human breast cancer applications for personalized therapy. J. Proteome Res.7, 1508–1517 (2008).
  • Anderson L, Seilhamer J. A comparison of selected mRNA and protein abundances in human liver. Electrophoresis18, 533–537 (1997).
  • Celis JE, Kruhoffer M, Gromova I et al. Gene expression profiling: monitoring transcription and translation products using DNA microarrays and proteomics. FEBS Lett.480, 2–16 (2000).
  • Gygi SP, Rist B, Gerber SA, Turecek F, Gelb MH, Aebersold R. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol.17, 994–999 (1999).
  • Nishizuka S, Charboneau L, Young L et al. Proteomic profiling of the NCI-60 cancer cell lines using new high-density reverse-phase lysate microarrays. Proc. Natl Acad. Sci. USA100, 14229–14234 (2003).
  • Zhou J, Wulfkuhle J, Zhang H et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc. Natl Acad. Sci. USA104, 16158–16163 (2007).
  • Boyd ZS, Wu QJ, O’Brien C et al. Proteomic analysis of breast cancer molecular subtypes and biomarkers of response to targeted kinase inhibitors using reverse-phase protein microarrays. Mol. Cancer Ther.7, 3695–3706 (2008).
  • Holdhoff M, Schmidt K, Donehower R, Diaz LA Jr. Analysis of circulating tumor DNA to confirm somatic KRAS mutations. J. Natl Cancer Inst.101, 1284–1285 (2009).
  • Maheswaran S, Sequist LV, Nagrath S et al. Detection of mutations in EGFR in circulating lung-cancer cells. N. Engl. J. Med.359, 366–377 (2008).
  • Yen LC, Yeh YS, Chen CW et al. Detection of KRAS oncogene in peripheral blood as a predictor of the response to cetuximab plus chemotherapy in patients with metastatic colorectal cancer. Clin. Cancer Res.15, 4508–4513 (2009).
  • Nagrath S, Sequist LV, Maheswaran S et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature450, 1235–1239 (2007).
  • Jhawer M, Goel S, Wilson AJ et al. PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to the epidermal growth factor receptor inhibitor cetuximab. Cancer Res.68, 1953–1961 (2008).
  • Loupakis F, Pollina L, Stasi I et al. PTEN expression and KRAS mutations on primary tumors and metastases in the prediction of benefit from cetuximab plus irinotecan for patients with metastatic colorectal cancer. J. Clin. Oncol.27, 2622–2629 (2009).
  • Berns K, Horlings HM, Hennessy BT et al. A functional genetic approach identifies the PI3K pathway as a major determinant of trastuzumab resistance in breast cancer. Cancer Cell12, 395–402 (2007).
  • Nagata Y, Lan KH, Zhou X et al. PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell6, 117–127 (2004).
  • Bekaii-Saab T. KRAS testing in metastatic colorectal cancer: implications on the use of biologic agents. Clin. Colorectal Cancer8, 135–140 (2009).
  • Jimeno A, Messersmith WA, Hirsch FR, Franklin WA, Eckhardt SG. KRAS mutations and susceptibility to cetuximab and panitumumab in colorectal cancer. Cancer J.15, 110–113 (2009).
  • Lievre A, Laurent-Puig P. Genetics: predictive value of KRAS mutations in chemoresistant CRC. Nat. Rev. Clin. Oncol.6, 306–307 (2009).
  • Cross J. DxS Ltd. Pharmacogenomics9, 463–467 (2008).
  • Hebbar M, Wacrenier A, Desauw C et al. Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer. Anticancer Drugs17, 855–857 (2006).
  • Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discov.3, 711–715 (2004).
  • Sleijfer S, Verweij J. The price of success: cost–effectiveness of molecularly targeted agents. Clin. Pharmacol. Ther.85, 136–138 (2009).
  • Ray T. Mass general hospital to genetically test all cancer patients within one year. Pharmacogenomics Reporter (2009).
  • Board RE, Thelwell NJ, Ravetto PF et al. Multiplexed assays for detection of mutations in PIK3CA. Clin Chem.54, 757–760 (2008).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.