Emerging agents for metastatic pancreatic cancer: spotlight on early phase clinical trials

被引:3
作者
Kang, Byung Woog [1 ]
Chau, Ian [2 ]
机构
[1] Kyungpook Natl Univ, Kyungpook Natl Univ Hosp, Sch Med, Dept Oncol Hematol, Daegu, South Korea
[2] Royal Marsden Hosp, Dept Med, London, Surrey, England
关键词
Pancreatic cancer; clinical trials; targeted therapy; immune checkpoint inhibitors; antibody drug conjugates; NAB-PACLITAXEL; OPEN-LABEL; MONOCLONAL-ANTIBODY; PLUS GEMCITABINE; DUCTAL ADENOCARCINOMA; II TRIAL; ANTITUMOR-ACTIVITY; DOSE-ESCALATION; SINGLE-CENTER; SOLID TUMORS;
D O I
10.1080/13543784.2021.1995354
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction Despite the recent development of new chemotherapeutic regimens and combination strategies, metastatic pancreatic cancer (mPC) still shows only a modest response to conventional cytotoxic agents. However, several novel therapeutic agents targeting the unique features of mPC are showing promise in clinical trials. Area covered This article reviews the current state of development of new agents targeting various systems and molecular pathways. We searched PubMed and clinicaltrials.gov in September 2021 with a special focus on ongoing early phase clinical trials to identify the promising therapeutic strategies for mPC. Expert opinion Extensive tumor heterogeneity, complex tumor microenvironment, genetic alterations of the oncogenic signaling pathways, metabolic dysregulation, and a low immunogenicity are hurdles for current treatment approaches. Ongoing research efforts strive to overcome these hurdles and are showing some promising early results.
引用
收藏
页码:1089 / 1107
页数:19
相关论文
共 187 条
[1]   Evolving Treatment Paradigms for Pancreatic Cancer [J].
Abbassi, Rami ;
Schmid, Roland M. .
VISCERAL MEDICINE, 2019, 35 (06) :362-372
[2]   Palliative chemotherapy in pancreatic cancer-treatment sequences [J].
Abbassi, Rami ;
Alguel, Hana .
TRANSLATIONAL GASTROENTEROLOGY AND HEPATOLOGY, 2019, 4
[3]   A phase I dose escalation trial of tremelimumab (CP-675,206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer [J].
Aglietta, M. ;
Barone, C. ;
Sawyer, M. B. ;
Moore, M. J. ;
Miller, W. H., Jr. ;
Bagala, C. ;
Colombi, F. ;
Cagnazzo, C. ;
Gioeni, L. ;
Wang, E. ;
Huang, B. ;
Fly, K. D. ;
Leone, F. .
ANNALS OF ONCOLOGY, 2014, 25 (09) :1750-1755
[4]   Oncogenic NRG1 Fusions: A New Hope for Targeted Therapy in Pancreatic Cancer [J].
Aguirre, Andrew J. .
CLINICAL CANCER RESEARCH, 2019, 25 (15) :4589-4591
[5]  
Al Baghdadi Tareq, 2019, JCO Precis Oncol, V3, P1, DOI 10.1200/PO.19.00124
[6]   Contextual regulation of pancreatic cancer stem cell phenotype and radioresistance by pancreatic stellate cells [J].
Al-Assar, Osama ;
Demiciorglu, Fevzi ;
Lunardi, Serena ;
Gaspar-Carvalho, Maria Manuela ;
McKenna, William Gillies ;
Muschel, Ruth M. ;
Brunner, Thomas B. .
RADIOTHERAPY AND ONCOLOGY, 2014, 111 (02) :243-251
[7]   Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial [J].
Alistar, Angela ;
Morris, Bonny B. ;
Desnoyer, Rodwige ;
Klepin, Heidi D. ;
Hosseinzadeh, Keyanoosh ;
Clark, Clancy ;
Cameron, Amy ;
Leyendecker, John ;
D'Agostino, Ralph, Jr. ;
Topaloglu, Umit ;
Boteju, Lakmal W. ;
Boteju, Asela R. ;
Shorr, Rob ;
Zachar, Zuzana ;
Bingham, Paul M. ;
Ahmed, Tamjeed ;
Crane, Sandrine ;
Shah, Riddhishkumar ;
Migliano, John J. ;
Pardee, Timothy S. ;
Miller, Lance ;
Hawkins, Gregory ;
Jin, Guangxu ;
Zhang, Wei ;
Pasche, Boris .
LANCET ONCOLOGY, 2017, 18 (06) :770-778
[8]   Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer [J].
Amatu, A. ;
Sartore-Bianchi, A. ;
Bencardino, K. ;
Pizzutilo, E. G. ;
Tosi, F. ;
Siena, S. .
ANNALS OF ONCOLOGY, 2019, 30 :VIII5-VIII15
[9]  
[Anonymous], 2021, Cancer Discov, V11, pOF4, DOI 10.1158/2159-8290.CD-NB2021-0313
[10]   Phase II open-label study of erlotinib in combination with gemcitabine in unresectable and/or metastatic adenocarcinoma of the pancreas: relationship between skin rash and survival (Pantar study) [J].
Aranda, E. ;
Manzano, J. L. ;
Rivera, F. ;
Galan, M. ;
Valladares-Ayerbes, M. ;
Pericay, C. ;
Safont, M. J. ;
Mendez, M. J. ;
Irigoyen, A. ;
Arrivi, A. ;
Sastre, J. ;
Diaz-Rubio, E. .
ANNALS OF ONCOLOGY, 2012, 23 (07) :1919-1925