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Physicians’ Education Resource is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Physicians’ Education Resource designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Focus on Apoptosis
Targeted Therapies in Oncology, Vol. 7, No. 1

1 AMA PRA Category 1 Credit(s)™
Release Date: December 30, 2009
Expiration Date: December 30, 2010

Publication Overview

Authors

Medical writer: Aarati Ranganathan, PhD; Medical writer: Tristin Abair, PhD; Reviewed by: Alex Adjei, MD, PhD; Reviewed by: D. Ross Camidge, MD, PhD; Reviewed by: Joyce O’Shaughnessy, MD

Overview and Purpose

This activity features two animated figures illustrating PARP Inhibition and the Instrinsic and Extrinsic Apoptotic Pathway. See one of these animated figures now! Login below to see more!

Current approaches to targeted therapy consist predominantly of monoclonal antibodies and small-molecule receptor tyrosine kinase inhibitors. While effective, there remain many potential targets for cancer therapy, including molecules involved in the repair of DNA damage and the regulation of apoptosis.

Repair of DNA damage caused by radiation and cytotoxic agents used in the treatment of breast cancer requires the proper functioning of several proteins, including poly(ADP-ribose) polymerase (PARP), BRCA1, and BRCA2. PARP is important in the repair of single-stranded DNA breaks, while BRCA1 and BRCA2 play a role in the repair of double-stranded DNA breaks. Mutation of BRCA1 or BRCA2 leads to increased tumor formation and confers increased sensitivity to PARP inhibition, perhaps due to synthetic lethality. This has led to investigation of several PARP inhibitors in patients with BRCA-mutated cancers as well as those with triple-negative (estrogen receptor/progesterone receptor/HER2–negative) disease, which shares a similar molecular profile with BRCA1- mutated cancers. This novel therapeutic strategy has the potential to increase treatment options for this difficult-to-treat aggressive tumor type as well as other tumors harboring mutations in DNA repair pathways.

Apoptosis is initiated by 2 independent pathways, the extrinsic and the intrinsic, that converge in the final caspase cascade, leading to cell death. Signaling from these pathways provides several opportunities for the design of anticancer therapies, and several novel apoptosis-inducing agents that have the potential to specifically target tumor cell death are currently in clinical development. These include agonistic agents that induce apoptosis through the extrinsic pathway components tumor necrosis factor–related apoptosis-inducing ligand receptor (TRAIL-R)1 and TRAIL-R2 and antisense oligonucleotides or small-molecule inhibitors of antiapoptotic regulators in the intrinsic and common apoptotic pathways. Agents in this class are in early-phase trials and have shown promising results when combined with traditional chemotherapies.

The purpose of this activity is to update physicians on recent clinical data concerning the feasibility of PARP inhibitors and inducers of apoptosis in the treatment of cancer.

Target Audience

This publication is intended for medical oncologists involved in the care of patients with solid tumors. No specific skills or knowledge other than a basic training in oncology is required for successful participation in this activity. 

Learning Objectives

Upon completion of this educational activity, you should be able to:

  • Examine the efficacy and safety of PARP inhibitors in the treatment of breast cancer
  • Evaluate early-phase data on proapoptotic TRAIL-R agonists in anticancer therapy
  • Define targets in the intrinsic and final apoptotic pathways that are being exploited in anticancer therapy

Instructions for Participation

  1. Read the following information before entering the educational activity.
  2. Complete the Pretest.
  3. Study the educational activity.
  4. Complete the Posttest.
  5. Answer the evaluation questions.
  6. After completion of the Pretest and successful completion of the Posttest and evaluation, you will receive your certificate online.

You will be permitted 2 attempts to successfully complete the Posttest.

CME credit will be granted for only 1 form of participation, either online or via the printed publication.

Complete the test(s) and evaluation by December 30, 2010 to receive your certificate online.

Read all of the conditions in the Activity Terms box below. You must accept the CME Activity Terms in order to continue:

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It is the policy of Physicians’ Education Resource to ensure balance, independence, objectivity, and scientific rigor in all of its educational activities. As an organization accredited by the Accreditation Council for Continuing Medical Education (ACCME), Physicians’ Education Resource requires everyone who is in a position to control the content of an educational activity, including spouses/partners, to disclose all relevant financial relationships with any commercial interest. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that create a conflict of interest. Physicians’ Education Resource has implemented a mechanism to identify and resolve all conflicts of interest prior to the activity.

Joyce O’Shaughnessy, MD
Paid Consultant – Biogen Idec, Genentech, Inc., Johnson & Johnson Services, Inc.; Speaker’s Bureau – Abraxis BioScience, LLC, Bristol-Myers Squibb Company, Eli Lilly and Company, sanofi-aventis U.S.

D. Ross Camidge, MD, PhD
Paid Consultant – Abbott Laboratories; Agennix, Inc.; Boehringer Ingelheim GmbH; EntreMed, Inc.; Genentech, Inc.; ImClone Systems Incorporated; Onyx Pharmaceuticals, Inc.; Takeda Pharmaceuticals

Alex Adjei, MD, PhD
Research Funding – Ardea Biosciences, Inc.; Eli Lilly and Company

PER Editorial Staff
No relevant relationships to disclose

This CME activity might include discussion of investigational and/or unlabeled uses of drugs. If the activity includes discussion of investigational and/or unlabeled uses of a drug, specific information is located on the title page. Please refer to the full prescribing information for each drug discussed in this activity for FDA-approved dosing, indications, and warnings.

Commercial Support
An educational grant for this activity was provided by Genentech BioOncology and sanofi-aventis U.S.

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Banner Illustration
Illustrators: Erin Moore, Pam Curry

Disclaimer

The views and opinions expressed in this activity are those of the authors and do not necessarily reflect the views of the sponsor, supporter, or publisher. Although great care has been taken in compiling and checking the information given in this activity to ensure accuracy, the authors and Physicians’ Education Resource and its servants or agents shall not be responsible or in any way liable for the continued currency of the information or for any errors, omissions, or inaccuracies in this activity, whether arising from negligence or otherwise howsoever or for any consequences arising therefrom.

Please consult full prescribing information for any drugs or procedures discussed within.

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©Copyright 2009 by Physicians’ Education Resource. No material may be reproduced in whole or in part, in any form, without written permission from the publisher.

All correspondence should be directed to:
Editor, Targeted Therapies in Oncology
Physicians’ Education Resource
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Suite 700
Dallas, TX 75219
Phone: (214) 367-3400
Fax: (214) 367-3304
E-mail: editor@cancerlearning.com

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Educational Grants

An educational grant for this activity was provided by:


  1. Genentech BioOncology
  2. sanofi-aventis U.S.