Workshop A | Tuesday, January 26
9:00am - 12:00pm EST | 6:00am - 9:00am PST

Employing PARP and PARG Inhibitors to Cause Replication Fork Stalling & Cancer Cell Death

Constitutive activation of the replication stress response (RSR) pathway and DNA damage repair system may prove to value therapeutic strategies for a range of cancers, whether in combination or exploited in improving chemotherapeutic efficiency through interfering with DNA replication to exert their functions.

This workshop will discuss:

  • Mechanisms of the replication stress response and DNA damage tolerance pathways
  • The role of HLTF in regulating damage tolerance and replication stress resistance through control of fork reversal and replication repriming
  • Understanding DNA damage tolerance responses in the context of cancer or ATR, PARP and PARG inhibitors
  • PARP enzyme connections to DNA replication and replication stress
  • Poly(ADP-ribose) contributions to damage signaling, chromatin organization, and cellular architecture
  • PARP1/PARP2 allostery and structural insights into PARP inhibitor type
  • PARP1, NAHD levels and mechanism for AIF dependent cell metabolism and caspase-independent cell death
  • PARylation-dePARylation kinetics control nano and meso-scale repair complexes
  • PARG as a molecular time machine for control of PAR-dependent replication repair responses and cancer cell death
John Pascal

John Pascal
Professor of Biochemistry & Molecular Medicine Faculty of Medicine

Université de Montréal

Karlene Cimprich

Karlene Cimprich
Professor of Chemical & Systems Biology

Stanford University

John Tainer

John Trainer

MD Anderson CancerCenter

Workshop B | Tuesday, January 26
1:00pm - 4:00pm EST | 10:00am - 1:00pm PST

Target Validation in the DDR

Targeting the DDR is an attractive therapeutic strategy as cells harbouring DDR defects can become reliant on other repair pathways for survival. Identifying which targets are
most suitable for multiple cancer indications remains a challenge.

This workshop will discuss:

  • Discovering the context specific DDR targets
  • Identification of cooperating targets drugs to further destabilize for protection in resistant disease
  • Biomarker specific vs biomarker agnostic
  • Mitigating against off target activity
  • Ensuring target selection is tumor specific
  • How can targets be narrowed down
  • Identifying targets against multiple indications
  • Specific gene nuances and biomarkers beyond single gene mutations
  • Tissue is the issue: tissue context for drug selection and biomarkers
  • Intraclass DDR inhibitor nuances
  • Combination therapy approaches to extend the benefits of DDRi to a broader/more biomarker agnostic population
patrick pilie

Patrick Pilié
Assistant Professor, Genitourinary Medical Oncology

MD Anderson Cancer Center