Pertuzumab and trastuzumab: the rationale way to synergy
Sandrine Richard,Frédéric Selle,Jean-Pierre Lotz,Ahmed Khalil,Joseph Gligorov,Daniele G. Soares +5 more
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TLDR
Preclinical and clinical data on pertuzumab are synthetised and the mechanisms underlying the synergistic activity of the combination pertuzuumab-trastuzuab which are essentially due to their complementary mode of action are highlighted.Abstract:
It has now been 15 years since the HER2-targeted monoclonal antibody trastuzumab was introduced in clinical and revolutionized the treatment of HER2-positive breast cancer patients. Despite this achievement, most patients with HER2-positive metastatic breast cancer still show progression of their disease, highlighting the need for new therapies. The continuous interest in novel targeted agents led to the development of pertuzumab, the first in a new class of agents, the HER dimerization inhibitors. Pertuzumab is a novel recombinant humanized antibody directed against extracellular domain II of HER2 protein that is required for the heterodimerization of HER2 with other HER receptors, leading to the activation of downstream signalling pathways. Pertuzumab combined with trastuzumab plus docetaxel was approved for the first-line treatment of patients with HER2-positive metastatic breast cancer and is currently used as a standard of care in this indication. In the neoadjuvant setting, the drug was granted FDA-accelerated approval in 2013. Pertuzumab is also being evaluated in the adjuvant setting. The potential of pertuzumab relies in the dual complete blockade of the HER2/3 axis when administered with trastuzumab. This paper synthetises preclinical and clinical data on pertuzumab and highlights the mechanisms underlying the synergistic activity of the combination pertuzumab-trastuzumab which are essentially due to their complementary mode of action.read more
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Mechanisms Underlying the Action and Synergism of Trastuzumab and Pertuzumab in Targeting HER2-Positive Breast Cancer
TL;DR: A thorough understanding of the molecular mechanisms underlying the action and synergism of trastuzumab and pertuzumAB is essential for moving forward to achieve high efficacy in treating HER2-positive breast cancer.
Journal ArticleDOI
Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy
TL;DR: Pertuzumab was found to be a safe and effective drug regardless of the patient age and hormone receptor status, and use was associated with severe cardiac toxicity in some cases; however, the risk of pertuzumAB-induced cardiac dysfunction was low.
Journal ArticleDOI
Comprehensive genomic landscape and precision therapeutic approach in biliary tract cancers.
Ryosuke Okamura,Razelle Kurzrock,Robert J. Mallory,Paul T. Fanta,Adam M. Burgoyne,Bryan M. Clary,Shumei Kato,Jason K. Sicklick +7 more
TL;DR: Evaluation of ctDNA and tissue‐DNA is feasible in biliary tract cancers and the molecularly matched therapeutic regimens based on genomic profiling showed a significantly longer progression‐free survival than unmatched regimens.
Journal ArticleDOI
Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer
Sean P. Kennedy,Sean P. Kennedy,Jeremy Z. R. Han,Neil Portman,Neil Portman,Max Nobis,Jordan F. Hastings,Kendelle J. Murphy,Sharissa L. Latham,Antonia L Cadell,Dushan Miladinovic,Gabriella R. Marriott,Yolande E. I. O’Donnell,Robert F. Shearer,James T. Williams,James T. Williams,Amaya Garcia Munoz,Thomas R. Cox,Thomas R. Cox,D. Neil Watkins,D. Neil Watkins,Darren N. Saunders,Darren N. Saunders,Paul Timpson,Paul Timpson,Elgene Lim,Elgene Lim,Walter Kolch,David R. Croucher,David R. Croucher,David R. Croucher +30 more
TL;DR: The interaction of ERBB2 with a number of non-canonical RTKs activates a compensatory signalling response following treatment with pertuzumab, although a counter-intuitive combination of ER BB2 antibody therapy and a kinase inhibitor can overcome this innate therapeutic resistance.
Journal ArticleDOI
New and Emerging Targeted Therapies for Advanced Breast Cancer
TL;DR: Novel targeted breast cancer treatments are summarized and the possible implications of combination therapy are explored, including immunotherapy and targeted therapy against critical checkpoints and/or pathways in cell growth.
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