An Introduction to DNA Damage Repair in Cancer: Beyond PARP

Slides:

Advertisements

Similar presentations

PARP Inhibitors for the treatment of MPNST

Advertisements

A trial for women with –‘Triple negative’ breast cancer (TNBC) –Localised to breast +/- lymph nodes –Recommended standard treatment involves NEPTUNE Taxane.

Can We Define Tumors That Will Respond to PARP Inhibitors? A Phase II Correlative Study of Olaparib in Advanced Serous Ovarian Cancer and Triple-Negative.

PCR Application: Can Breast Cancer be Cured?. Normal, Healthy Cells Cells can change or differentiate to become specialised according to the tissue that.

Princess Margaret Hospital, Co-Chair Gynecology, NCIC CTG

PARP Inhibition: A New Approach To Cancer Therapy? Dr. Geert Kolvenbag

BRCA Mutations and Breast Cancer Ruth Phillips and Patty Ashby.

Panagiotis Konstantinopoulos MD, PhD Assistant Professor of Medicine

BRCA2 Clark Cunningham March 26, 2015 BIOL445 American Cancer Society, eastcancer/make-a-pink-ribbon-lapel-pin,

BRCA1 and Breast Cancer Madeline Ryan 3/17/2015.

University of Texas, Southwestern Medical Center, Dallas TX

A Randomized Phase 2 Trial Comparing Efficacy of the Combination of the PARP-inhibitor Olaparib and the Anti-angiogenic Cediranib Against Olaparib Alone.

Audeh MW et al. ASCO 2009; Abstract (Clinical Science Symposium)

Clinical and Research Updates in Gynecologic Oncology

Homologous recombination deficiency (HRD) of high grade serous ovarian tumors from the NOVA Phase III clinical study Keith Wilcoxen,1 Christopher Neff,2.

Fostering a Collaborative Approach in the Management of BRCA-Mutated Ovarian Cancer.

Targeting the DNA Damage Response in Cancer

A New Path Forward: Immune Checkpoint Inhibitors in Bladder Cancer

Steps to Optimizing Outcomes in Patients With Advanced Prostate Cancer

Breast cancer is the most common cancer among women

PARP Inhibition: The New Frontier in Recurrent Ovarian Cancer

BRCA, HRR Deficiency, and PARP Inhibitors

Discussion Outline Cells of the Immune System.

Essential Concepts in Harnessing the Immune System in Head and Neck Cancer.

The Nurse View.

MOCA Living Well: Understanding PARP Inhibitors in Ovarian Cancer

Metastatic Renal Cell Carcinoma

PARP and Other DNA Damage Repair Inhibitors in Solid Tumors: An Update

Activity Goals. Perspectives on PARP Inhibitors in Ovarian Cancer Has the Time Come for Individualized Care?

Program Goals. The Clinical Impact of Second-Generation Antihormonal Therapy in the Treatment of mCRPC.

PARP Inhibitors and Cancer: What Do You Need to Know?

Tailoring Hemophilia Prophylaxis Therapy

Counseling Patients About Germline BRCA Mutations

PARPi combinations against HR-proficient tumors.

Managing gBRCA-Positive Metastatic Breast Cancer

Optimizing Combination Endocrine Therapy in HR-Positive Advanced Breast Cancer.

Individualizing Care in Ovarian Cancer

A Spotlight on PI3K Inhibition in Relapsed/Refractory B-Cell Lymphoma

PCSK9 Inhibitors – A Leap in the Evolution of Dyslipidemia Management?

This program will include a discussion of off-label treatment and investigational agents not approved by the FDA for use in the United States, and data.

Maintenance Therapy in Advanced Ovarian Cancer

PARP Inhibitors.

Phase II study on the combination of trabectedin and olaparib for advanced, platinum-resistant ovarian cancer Dr Giorgio Valabrega University of Torino,

Volume 137, Issue 2, Pages (May 2015)

Molecular Testing in Ovarian Cancer: Is the Time Now?

This program will include a discussion of off-label treatment and investigational agents not approved by the FDA for use in the US, and data that were.

The Changing Field of Melanoma: Ipilimumab.

PARP Inhibitors in Cancer Therapy: Promise, Progress, and Puzzles

EVOLUTION OF PARP INHIBITORS IN OVARIAN CANCER

Challenges and Opportunities

Preparing for Checkpoint Inhibitors in Breast Cancer

How Can Precision Medicine in Oncology Refine Best Treatment Approach?

Novel Concepts in the Management of RCC

PROSTATE CANCER CIRCULATING BIOMARKER CONSENSUS STATEMENT QUESTIONS

Translating Germline Cancer Risk into Precision Prevention

PARP Inhibitors in Cancer Therapy: Promise, Progress, and Puzzles

Figure 3 Nuclear-penetrating autoantibodies and synthetic lethality

Volume 147, Issue 3, Pages (December 2017)

Checkpoint Inhibitors in First-Line Advanced NSCLC

Volume 5, Issue 1, Pages (January 2019)

TGF-β Inhibition and Immunotherapy: Checkmate

Introduction. Welcome to this program, titled De-Escalating Therapy in Epilepsy: A Return to Monotherapy.

What Does BRCA Have to Do With It? PARP Inhibitors in Ovarian Cancer

Efficacy of BSI-201, a PARP Inhibitor, in Combination with Gemcitabine/Carboplatin (GC) in Triple Negative Metastatic Breast Cancer (mTNBC): Results.

Current Status of Biomarkers for Immune Checkpoint Inhibitors

Clinical Focus.

Identifying TRK Fusions in Head and Neck Cancer

Changes in tumor sizes, CA-125, serum ceruloplasmin, and copper levels in 5 patients with platinum-resistant high-grade epithelial ovarian cancer who received.

Combined inhibition of Wee1 and PARP causes persistent radiation-induced DNA damage. Combined inhibition of Wee1 and PARP causes persistent radiation-induced.

Optimizing Patient Outcomes in Metastatic Triple-Negative Breast Cancer.

Presentation transcript:

An Introduction to DNA Damage Repair in Cancer: Beyond PARP

Program Goals

Discussion Overview

DNA Repair

ABCs of DNA Repair

DNA Repair Defects in Cancer

DNA Repair Defects: The Achilles’ Heel in Cancer Cells

Synthetic Lethality

PARP and Synthetic Lethality

Increased Sensitivity of BRCA1-/- and BRCA2-/- Cells to PARP Inhibition

PARP Inhibitors

"BRCAness"

Sensitivity to PARP Inhibition in Cells Deficient for DNA Repair

What Have We Learned From Clinical Trials of PARP Inhibitors?

Inhibition of PARP in Tumors From Carriers of BRCA Mutations

Platinum-Free Interval Relative to Olaparib Sensitivity

Platinum Sensitivity in BRCA1-/- Ovarian Cancer Patient After PD on Olaparib

Class Effect of PARP Inhibitors

Olaparib Induces Responses in mCRPC

PARP Inhibition in Patients Heterozygous for ATM

Targeting DNA Repair Beyond PARP

Targeting DNA Repair Through ATR

ATR Inhibitor VX-970

VX-970 Monotherapy Complete Response

Combination Therapies Potentially Synergistic With DNA Repair

Other Targetable DNA Repair Defects

Conclusions

Abbreviations

Abbreviations (cont)

Abbreviations (cont)

Abbreviations (cont)