Targeted Therapies in Cancer: An Update

Marc Lacroix
Université Libre de Bruxelles, Baelen, Belgium

Series: Cancer Etiology, Diagnosis and Treatments
BISAC: MED062000

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Besides surgery, radiation therapy, endocrine therapy or chemotherapy, which were widely used in cancer patients for decades, the 21st century has seen the emergence of “targeted” therapy, resulting from the identification of molecular pathways in cells and their alterations in tumors. An increasing number of compounds targeting specific molecules or cancer cells have been developed and, for some of them, approved by the United States Food and Drug Administration (FDA) as well as other regulators in EU and Japan Additional new and more efficient types of compounds, are still in clinical trials, but are expected to gain future approval.

More than eighty FDA-approved targeted therapies are described here, along with about eighty other promising compounds. These drugs are members of various therapy classes, including tyrosine kinase inhibitors; serine/threonine kinase inhibitors; dual specificity kinase inhibitors; lipid kinase inhibitors; poly ADP ribose polymerase inhibitors; monoclonal antibodies; microtubule targeting agents; histone deacetylase inhibitors; proteasome inhibitors; antimetabolites; immunomodulatory agents; DNA methyltransferase inhibitors; hedgehog pathway inhibitors; enzymes; protein translation inhibitors; vaccines, oncolytic viruses; chimeric antigen receptor T-cells (CAR-T); and so on.

A series of “companion” diagnostics intended to be used as an indication for specific therapies, and approved to this aim are also mentioned.

The book aims to present the broad landscape of compounds and companion diagnostics that are expected to pave the way towards a future of hope for cancer patients. (Imprint: Nova Biomedical)

Preface

Abbreviations

Chapter 1. Innovation in the Biopharmaceutical Pipeline

Chapter 2. The Diversity of Targeted Cancer Drugs Recently Approved by the FDA

Chapter 3. Chronological List of Targeted Cancer Drugs Approved by the FDA

Chapter 4. Targeted Therapies: Detailed Description

Chapter 5. Targeted Therapies in the Pipe-Line

Chapter 6. Companion Diagnostics for Targeted Therapies

About the Author

Index

Chapter 1

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About developing a new drug from original idea to the launch of a finished product, see also:
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Chapter 2

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West AC, Johnstone RW. New and emerging HDAC inhibitors for cancer treatment. J Clin Invest. 2014 Jan 2;124(1):30-9.
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Chapter 3

Martell RE, Sermer D, Getz K, Kaitin K. Oncology drug development and approval of systemic anticancer therapy by the U.S. Food and Drug Administration. Oncologist. 2013;18(1):104-11.

Chapter 6

Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, Dobrovic A, Birrer MJ, Webb PM, Stewart C et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 2012 Jul 20;30(21):2654-63.
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Dietel M, Jöhrens K, Laffert MV, Hummel M, Bläker H, Pfitzner BM, Lehmann A, Denkert C, Darb-Esfahani S, Lenze D et al. A 2015 update on predictive molecular pathology and its role in targeted cancer therapy: a review focussing on clinical relevance. Cancer Gene Ther. 2015 Sep;22(9):417-30.
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Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, Akimov M, Bufill JA, Lee C, Jentz D et al. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015 Aug;5(8):
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Martin V, Cappuzzo F, Mazzucchelli L, Frattini M. HER2 in solid tumors: more than 10 years under the microscope; where are we now? Future Oncol. 2014 Jun;10(8):1469-86.
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Pall G. The next-generation ALK inhibitors. Curr Opin Oncol. 2015 Mar;27(2):118-24.
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Rimawi MF, Schiff R, Osborne CK. Targeting HER2 for the treatment of breast cancer. Annu Rev Med. 2015;66:111-28.
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Tan CS, Gilligan D, Pacey S. Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. Lancet Oncol. 2015 Sep;16(9):e447-59.
Torres-Cabala CA1, Wang WL, Trent J, Yang D, Chen S, Galbincea J, Kim KB, Woodman S, Davies M, Plaza JA. Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acral-lentiginous/mucosal type. Mod Pathol. 2009 Nov;22(11):1446-56.
Tremblay D, Carreau N, Kremyanskaya M, Mascarenhas J. Systemic Mastocytosis: Clinical Update and Future Directions. Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):728-38.
Tronnier M, Mitteldorf C. Treating advanced melanoma: current insights and opportunities. Cancer Manag Res. 2014 Sep 10;6:349-56.
Won E, Janjigian YJ, Ilson DH. HER2 directed therapy for gastric/esophageal cancers. Curr Treat Options Oncol. 2014 Sep;15(3):395-404.
Zhang W. BRAF inhibitors: the current and the future. Curr Opin Pharmacol. 2015 Aug;23:68-73.

Audience: Academic level: the book is intended for MSc, MD, PhD’s and, more generally, to researchers in oncology. However, it may be of interest for people in pharmaceutical industry, since there is a continuous search for new gene-based targeted therapies.

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