Role of Targeted Agents in Metastatic Colorectal Cancer

Overview

Journal Target Oncol

Specialty Oncology

Date 2013 May 7

PMID 23645285

Citations 33

Authors

Hans Prenen

Loredana Vecchione

Eric Van Cutsem

Affiliations

Soon will be listed here.

Abstract

Despite a decrease in incidence and mortality, colorectal cancer (CRC) still represents the second leading cause of cancer worldwide. Recurrence following surgery and adjuvant treatment and the metastatic disease are still a major problem with a median overall survival of approximately 24 months. Nevertheless, there has been an improvement in outcome due to the introduction into clinical practice of new cytotoxic and targeted agents. The targeted agents that have improved the efficacy of the available chemotherapeutic regimens in CRC are the ones that target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). In particular, bevacizumab, a recombinant humanized monoclonal antibody against VEGF, cetuximab, and panitumumab, two monoclonal antibodies that target the EGFR, have been approved for the treatment of metastatic CRC (mCRC). While for anti-EGFR agents, predictive biomarkers have been found, no good biomarkers have been found yet for anti-VEGF agents. Aflibercept and regorafenib have recently also been approved in patients with mCRC. This article reviews in an extensive way the data of large randomized clinical trials for the use of anti-VEGF and anti-EGFR in CRC. Aim of this review is also to describe the current status of biomarkers discovery and highlight how to improve the therapeutic index of these targeted agents by selecting in advance the subgroup of patients who will benefit from these treatments.

Citing Articles

Concurrent chemoradiotherapy combined with nimotuzumab in stage III-IVa nasopharyngeal carcinoma: a retrospective analysis.

Cai Z, Chen D, Qiu W, Liang C, Huang Y, Zhou J J Cancer Res Clin Oncol. 2022; 149(6):2327-2344.

PMID: 36289067 DOI: 10.1007/s00432-022-04355-w.

The lymphatic vasculature: An active and dynamic player in cancer progression.

Rezzola S, Sigmund E, Halin C, Ronca R Med Res Rev. 2021; 42(1):576-614.

PMID: 34486138 PMC: 9291933. DOI: 10.1002/med.21855.

Downregulating Long Non-coding RNAs CTBP1-AS2 Inhibits Colorectal Cancer Development by Modulating the miR-93-5p/TGF-β/SMAD2/3 Pathway.

Li Q, Li M, Jiang Z, Hou Z, Liu W, Ma N Front Oncol. 2021; 11:626620.

PMID: 33937030 PMC: 8079788. DOI: 10.3389/fonc.2021.626620.

Docosahexaenoic acid inhibits both NLRP3 inflammasome assembly and JNK-mediated mature IL-1β secretion in 5-fluorouracil-treated MDSC: implication in cancer treatment.

Dumont A, De Rosny C, Kieu T, Perrey S, Berger H, Fluckiger A Cell Death Dis. 2019; 10(7):485.

PMID: 31217433 PMC: 6584690. DOI: 10.1038/s41419-019-1723-x.

Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer.

Nowak-Sliwinska P, Scapozza L, Ruiz i Altaba A Biochim Biophys Acta Rev Cancer. 2019; 1871(2):434-454.

PMID: 31034926 PMC: 6528778. DOI: 10.1016/j.bbcan.2019.04.005.

References

Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D . Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012; 486(7404):532-6. PMC: 3927413. DOI: 10.1038/nature11156. View

Yonesaka K, Zejnullahu K, Okamoto I, Satoh T, Cappuzzo F, Souglakos J . Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic antibody cetuximab. Sci Transl Med. 2011; 3(99):99ra86. PMC: 3268675. DOI: 10.1126/scitranslmed.3002442. View

Price T, Hardingham J, Lee C, Weickhardt A, Townsend A, Wrin J . Impact of KRAS and BRAF Gene Mutation Status on Outcomes From the Phase III AGITG MAX Trial of Capecitabine Alone or in Combination With Bevacizumab and Mitomycin in Advanced Colorectal Cancer. J Clin Oncol. 2011; 29(19):2675-82. DOI: 10.1200/JCO.2010.34.5520. View

Roberts R, Min L, Washington M, Olsen S, Settle S, Coffey R . Importance of epidermal growth factor receptor signaling in establishment of adenomas and maintenance of carcinomas during intestinal tumorigenesis. Proc Natl Acad Sci U S A. 2002; 99(3):1521-6. PMC: 122223. DOI: 10.1073/pnas.032678499. View

Siegel R, Ward E, Brawley O, Jemal A . Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011; 61(4):212-36. DOI: 10.3322/caac.20121. View

Souglakos J, Philips J, Wang R, Marwah S, Silver M, Tzardi M . Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer. 2009; 101(3):465-72. PMC: 2720232. DOI: 10.1038/sj.bjc.6605164. View

Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H . Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Cancer. 2006; 120(4):781-7. DOI: 10.1002/ijc.22370. View

Peeters M, Price T, Cervantes A, Sobrero A, Ducreux M, Hotko Y . Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010; 28(31):4706-13. DOI: 10.1200/JCO.2009.27.6055. View

Welch S, Spithoff K, Rumble R, Maroun J . Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review. Ann Oncol. 2009; 21(6):1152-1162. DOI: 10.1093/annonc/mdp533. View

10.

Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P . Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26(35):5705-12. DOI: 10.1200/JCO.2008.18.0786. View

11.

Cappuzzo F, Finocchiaro G, Rossi E, Janne P, Carnaghi C, Calandri C . EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol. 2007; 19(4):717-23. DOI: 10.1093/annonc/mdm492. View

12.

Bertotti A, Migliardi G, Galimi F, Sassi F, Torti D, Isella C . A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discov. 2012; 1(6):508-23. DOI: 10.1158/2159-8290.CD-11-0109. View

13.

Ellis L, Hicklin D . VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008; 8(8):579-91. DOI: 10.1038/nrc2403. View

14.

Sato T, Vries R, Snippert H, van de Wetering M, Barker N, Stange D . Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009; 459(7244):262-5. DOI: 10.1038/nature07935. View

15.

Fiske W, Threadgill D, Coffey R . ERBBs in the gastrointestinal tract: recent progress and new perspectives. Exp Cell Res. 2008; 315(4):583-601. PMC: 2941795. DOI: 10.1016/j.yexcr.2008.10.043. View

16.

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

17.

De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G . Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010; 11(8):753-62. DOI: 10.1016/S1470-2045(10)70130-3. View

18.

Karapetis C, Khambata-Ford S, Jonker D, OCallaghan C, Tu D, Tebbutt N . K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008; 359(17):1757-65. DOI: 10.1056/NEJMoa0804385. View

19.

Grothey A, Sargent D, Goldberg R, Schmoll H . Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004; 22(7):1209-14. DOI: 10.1200/JCO.2004.11.037. View

20.

Giantonio B, Catalano P, Meropol N, ODwyer P, Mitchell E, Alberts S . Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007; 25(12):1539-44. DOI: 10.1200/JCO.2006.09.6305. View