Molecular targeted therapies for pancreatic cancer

被引:51
作者
Borja-Cacho, Daniel [1 ]
Jensen, Eric Hans [1 ]
Saluja, Ashok Kumar [1 ]
Buchsbaum, Donald J. [2 ]
Vickers, Selwyn Maurice [1 ]
机构
[1] Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA
[2] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL USA
关键词
death receptor; epidermal growth factor receptor; molecular targeted therapy; pancreatic cancer; vascular endothelial growth factor;
D O I
10.1016/j.amjsurg.2008.04.009
中图分类号
R61 [外科手术学];
学科分类号
摘要
BACKGROUND: Pancreatic cancer cells express different mutations that increase the aggressiveness and confer resistance to conventional chemotherapy and radiotherapy. Molecules that selectively bind and inhibit these mutations are effective in other solid tumors and are now emerging as a complementary therapy in pancreatic cancer. The objective of this review is to describe the effect of drugs that inhibit specific mutations present in pancreatic cancer with special emphasis on clinical trials. DATA SOURCES: We reviewed the English-language literature (MedLine) addressing the role of drugs that target mutations present in pancreatic cancer. Both preclinical and clinical studies were included. CONCLUSIONS: Preclinical evidence supports the combination of conventional approved therapies plus drugs that block epidermal growth factor receptor and vascular growth endothelial factor or induce apoptosis. However. most of the current clinical evidence is limited to small phase I trials evaluating the toxicity and safety of these regimens. The results of additional randomized trials that are still undergoing will clarify the role of these drugs in pancreatic cancer. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:430 / 441
页数:12
相关论文
共 90 条
  • [41] Nuclear factor-κB maintains TRAIL resistance in human pancreatic cancer cells
    Khanbolooki, Sanaz
    Nawrocki, Steffan T.
    Arumugam, Thiruvengadam
    Andtbacka, Robert
    Pino, Maria S.
    Kurzrock, Razelle
    Logsdon, Craig D.
    Abbruzzese, James L.
    McConkey, David J.
    [J]. MOLECULAR CANCER THERAPEUTICS, 2006, 5 (09) : 2251 - 2260
  • [42] Antitumor effect of trastuzumab for pancreatic cancer with high HER-2 expression and enhancement of effect by combined therapy with gemcitabine
    Kimura, Kenjiro
    Sawada, Tetsuji
    Komatsu, Midori
    Inoue, Masafumi
    Muguruma, Kazuya
    Nishihara, Tamahiro
    Yamashita, Yoshito
    Yamada, Nobuya
    Ohira, Masaichi
    Hirakawa, Kosei
    [J]. CLINICAL CANCER RESEARCH, 2006, 12 (16) : 4925 - 4932
  • [43] Phase II trial of bevacizurnab plus gemcitabine in patients with advanced pancreatic cancer
    Kindler, HL
    Friberg, G
    Singh, DA
    Locker, G
    Nattam, S
    Kozloff, M
    Taber, DA
    Karrison, T
    Dachman, A
    Stadler, WM
    Vokes, EE
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (31) : 8033 - 8040
  • [44] Pancreatic cancer-associated stroma production
    Korc, Murray
    [J]. AMERICAN JOURNAL OF SURGERY, 2007, 194 (4A) : S84 - S86
  • [45] Randomized phase II - study evaluating EGFR targeting therapy with Cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer - PARC: study protocol [ISRCTN56652283]
    Krempien, R
    Muenter, MW
    Huber, PE
    Nill, S
    Friess, H
    Timke, C
    Didinger, B
    Buechler, P
    Heeger, S
    Herfarth, KK
    Abdollahi, A
    Buchler, MW
    Debus, J
    [J]. BMC CANCER, 2005, 5 (1)
  • [46] Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-κB-regulated gene products
    Kunnumakkara, Ajaikumar B.
    Guha, Sushovan
    Krishnan, Sunil
    Diagaradjane, Parmeswaran
    Gelovani, Juri
    Aggarwal, Bharat B.
    [J]. CANCER RESEARCH, 2007, 67 (08) : 3853 - 3861
  • [47] Impact of vascular endothelial growth factor-C and -D expression in human pancreatic cancer: Its relationship to lymph node metastasis
    Kurahara, H
    Takao, S
    Maemura, K
    Shinchi, H
    Natsugoe, S
    Aikou, T
    [J]. CLINICAL CANCER RESEARCH, 2004, 10 (24) : 8413 - 8420
  • [48] Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas
    Kwak, Eunice L.
    Jankowski, Janusz
    Thayer, Sarah P.
    Lauwers, Gregory Y.
    Brannigan, Brian W.
    Harris, Patricia L.
    Okimoto, Ross A.
    Haserlat, Sara M.
    Driscoll, David R.
    Ferry, David
    Muir, Beth
    Settleman, Jeff
    Fuchs, Charles S.
    Kulke, Matthew H.
    Ryan, David P.
    Clark, Jeff W.
    Sgroi, Dennis C.
    Haber, Daniel A.
    Bell, Daphne W.
    [J]. CLINICAL CANCER RESEARCH, 2006, 12 (14) : 4283 - 4287
  • [49] Nuclear factor-κB and IκB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis
    Li, L
    Aggarwal, BB
    Shishodia, S
    Abbruzzese, J
    Kurzrock, R
    [J]. CANCER, 2004, 101 (10) : 2351 - 2362
  • [50] Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
    Lynch, TJ
    Bell, DW
    Sordella, R
    Gurubhagavatula, S
    Okimoto, RA
    Brannigan, BW
    Harris, PL
    Haserlat, SM
    Supko, JG
    Haluska, FG
    Louis, DN
    Christiani, DC
    Settleman, J
    Haber, DA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (21) : 2129 - 2139