Abstract
Cancer is currently the second leading cause of death globally and is expected to be responsible for approximately 9.6 million deaths in 2018. With an unprecedented understanding of the molecular pathways that drive the development and progression of human cancers, novel targeted therapies have become an exciting new development for anti-cancer medicine. These targeted therapies, also known as biologic therapies, have become a major modality of medical treatment, by acting to block the growth of cancer cells by specifically targeting molecules required for cell growth and tumorigenesis. Due to their specificity, these new therapies are expected to have better efficacy and limited adverse side effects when compared with other treatment options, including hormonal and cytotoxic therapies. In this review, we explore the clinical development, successes and challenges facing targeted anti-cancer therapies, including both small molecule inhibitors and antibody targeted therapies. Herein, we introduce targeted therapies to epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), anaplastic lymphoma kinase (ALK), BRAF, and the inhibitors of the T-cell mediated immune response, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein-1 (PD-1)/ PD-1 ligand (PD-1 L).
Highlights
Around 1 in 6 deaths are attributed to cancer, making it the second leading cause of death [1]
epidermal growth factor receptor (EGFR) gene amplifications are common, with studies showing that up to 50% of Colorectal cancer (CRC) and non–small cell lung cancer (NSCLC) demonstrate a marked increase in EGFR
BRAF plays an integral role in regulating cell proliferation in response to growth signals
Summary
Around 1 in 6 deaths are attributed to cancer, making it the second leading cause of death [1]. Vandetanib, which targets both EGFR and VEGF, has been FDA approved for the treatment of medullary thyroid cancers in patients with unresectable, locally advanced, or metastatic disease [75] This occurred following the ‘ZETA’ Phase III clinical trial data demonstrating improvement in PFS (30.5 vs 19.2 months) compared with the placebo treated controls (Table 1) [94]. Tesevatinib, nazartinib and PF-06747775 are currently in phase II/III trials to assess their activity against NSCLCs. Clinical development of monoclonal antibodies targeting EGFR To date, three anti-EGFR mAbs, cetuximab (Erbitux®, Bristol-Myers Squibb/Merck KGaA), panitumumab (ABX-EGF/ Vectibix®, Amgen), and necitumumab (Portrazza®, Eli Lilly and Company, USA), are currently in widespread use in cancer treatment, most notably for CRC. Necitumumab is currently not indicated for the treatment of non-squamous NSCLC
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