Emerging drugs in the treatment of pancreatic cancer

被引:12
作者
Mahalingam, Devalingam [1 ]
Kelly, Kevin R. [1 ]
Swords, Ronan T. [1 ]
Carew, Jennifer [1 ]
Nawrocki, Steffan T. [1 ]
Giles, Francis J. [1 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Inst Drug Dev, Div Canc Res & Therapy Ctr, San Antonio, TX 78229 USA
关键词
apoptosis and hedgehog pathway; EGFR; HDAC; IGF-1R; K-Ras; pancreatic cancer; STAT3; targeted therapies; VEGF; PHASE-III TRIAL; GROWTH-FACTOR RECEPTOR; SMALL-CELL LUNG; SIGNAL TRANSDUCER; PLUS GEMCITABINE; TGF-BETA; I TRIAL; ABERRANT METHYLATION; ADENOCARCINOMA CELLS; PROTEIN TRANSFERASE;
D O I
10.1517/14728210902972502
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background: Pancreatic cancer is the fourth leading cause of cancer-related death in the US. However, there is a growing belief that novel biological agents could improve survival of patients with this cancer. Gemcitabine-based chemotherapy remains the cornerstone treatment for advanced pancreatic cancers. So far, the current targeted agents that have been used in combination with gemcitabine have failed to improve clinical outcomes. This failure may stem from the heterogeneous molecular pathogenesis of pancreatic cancers, which involves several oncogenic pathways and defined genetic mutations. Objective: The aims of this review are: i) to define the existing treatments available at present for patients with pancreatic cancers in the neo-adjuvant, adjuvant, locally advanced and metastatic settings; ii) to highlight the molecular heterogeneity of the cancers and the rationale for targeting specific oncogenic pathways; iii) to give an overview of targeted agents that may potentially have an impact in the treatment of pancreatic cancers. Conclusions: Molecular pathogenesis of pancreatic cancer involves several pathways and defined genetic mutations. Targeting these complex molecular pathways with a combination of novel biological and chemotherapeutic agents could potentially improve patient outcome.
引用
收藏
页码:311 / 328
页数:18
相关论文
共 168 条
[91]   eIF4E - from translation to transformation [J].
Mamane, Y ;
Petroulakis, E ;
Rong, LW ;
Yoshida, K ;
Ler, LW ;
Sonenberg, N .
ONCOGENE, 2004, 23 (18) :3172-3179
[92]   Aberrant methylation of the human hedgehog interacting protein (HHIP) gene in pancreatic neoplasms [J].
Martin, ST ;
Sato, N ;
Dhara, S ;
Chang, R ;
Hustinx, SR ;
Abe, T ;
Maitra, A ;
Goggins, M .
CANCER BIOLOGY & THERAPY, 2005, 4 (07) :728-733
[93]   Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-H gemcitabine infusion, in locally advanced pancreatic cancer [J].
Maurel, Joan ;
Martin-Richard, Marta ;
Conill, Carlos ;
Sanchez, Marcelo ;
Petriz, Lourdes ;
Gines, Angels ;
Miquel, Rosa ;
Gallego, Rosa ;
Cajal, Rosana ;
Ayuso, Carmen ;
Navarro, Salvador ;
Marmol, Maribel ;
Nadal, Cristina ;
Auge, Josep Maria ;
Fernandez-Cruz, Laureano ;
Gascon, Pere .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 2006, 66 (05) :1391-1398
[94]   A phase I dose-finding study of sunitinib (SU) in combination with gemcitabine (G) in patients (pts) with advanced solid tumors [J].
Michaelson, M. D. ;
Schwarzberg, A. ;
Ryan, D. P. ;
McDermott, D. F. ;
Shapiro, G. I. ;
Tye, L. ;
Chen, I. ;
Selaru, P. ;
Wang, E. ;
Zhu, A. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (15)
[95]  
MILELLA M, 2008, ASCO M 2008 MAY 20 S, V26, P4637
[96]   Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer [J].
Miller, Kathy ;
Wang, Molin ;
Gralow, Julie ;
Dickler, Maura ;
Cobleigh, Melody ;
Perez, Edith A. ;
Shenkier, Tamara ;
Cella, David ;
Davidson, Nancy E. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (26) :2666-2676
[97]   Growth delay of human pancreatic cancer cells by methylase inhibitor 5-aza-2′-deoxycytidine treatment is associated with activation of the interferon signalling pathway [J].
Missiaglia, E ;
Donadelli, M ;
Palmieri, M ;
Crnogorac-Jurcevic, T ;
Scarpa, A ;
Lemoine, NR .
ONCOGENE, 2005, 24 (01) :199-211
[98]   Deforolimus (AP23573) a novel mTOR inhibitor in clinical development [J].
Mita, Monica ;
Sankhala, Kamalesh ;
Abdel-Karim, Issam ;
Mita, Alain ;
Giles, Francis .
EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2008, 17 (12) :1947-1954
[99]   Immunohistochemical analysis of Bcl-2, Bax, Bcl-X, and Mcl-1 expression in pancreatic cancers [J].
Miyamoto, Y ;
Hosotani, R ;
Wada, M ;
Lee, JU ;
Koshiba, T ;
Fujimoto, K ;
Tsuji, S ;
Nakajima, S ;
Doi, R ;
Kato, M ;
Shimada, Y ;
Imamura, M .
ONCOLOGY, 1999, 56 (01) :73-82
[100]   Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada clinical trials group [J].
Moore, Malcolm J. ;
Goldstein, David ;
Hamm, John ;
Figer, Arie ;
Hecht, Joel R. ;
Gallinger, Steven ;
Au, Heather J. ;
Murawa, Pawel ;
Walde, David ;
Wolff, Robert A. ;
Campos, Daniel ;
Lim, Robert ;
Ding, Keyue ;
Clark, Gary ;
Voskoglou-Nomikos, Theodora ;
Ptasynski, Mieke ;
Parulekar, Wendy .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (15) :1960-1966