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Refractory Metastatic Colorectal Cancer: Current Challenges and Future Prospects

Authors Lam M, Lum C, Latham S, Tipping Smith S, Prenen H, Segelov E

Received 13 May 2020

Accepted for publication 26 June 2020

Published 15 July 2020 Volume 2020:12 Pages 5819—5830


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li

Marissa Lam,1 Caroline Lum,1 Sarah Latham,1 Sam Tipping Smith,1 Hans Prenen,2 Eva Segelov1,3

1Department of Medical Oncology, Monash Medical Center, Clayton, Australia; 2Department of Oncology, University Hospital Antwerp, Edegem, Belgium; 3Faculty of Medicine, Monash University, Clayton, Australia

Correspondence: Eva Segelov Level 7 MHTP, Monash Health 246 Clayton Road, Clayton VIC 3168, Australia
Tel +613 85722392
Fax +613 8572 2446

Abstract: Despite advances, patients with metastatic colorectal cancer (mCRC) still have poor long-term survival. Identification of molecular subtypes is important to guide therapy through standard treatment pathways and holds promise for the development of new treatments. Following standard first- and second-line chemotherapy plus targeted agents, many patients retain a reasonable performance status, and thus are seeking further effective treatment to extend life and maintain symptom control. The challenge lies in selecting the most appropriate therapy in the third- and fourth-line settings, from a range of options including the relatively new oral agents TAS-102 and regorafenib, or rechallenge with previous chemotherapy or anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (mAB). Beyond this, therapy consists of trials involving novel agents and new combinations of treatments with theoretical synergy and/or non-overlapping toxicity. There is a great focus on enhancing immunogenicity in mCRC, to reflect the impressive results of immunotherapy drugs in the small cohort with mismatch repair deficient (dMMR) mCRC. Rare molecular subtypes of mCRC are increasingly being identified, including Her2-positive disease, NTRK fusions and others. Clinical trials exploring the efficacy of immunomodulatory and precision agents are plentiful and will hopefully yield clinically meaningful results that can be rapidly translated into routine care.

Keywords: molecular targets, genomic profiling, immunotherapy, precision medicine

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