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DNA Damage Response

DNA damage and replication stress play a major role in disease and are a hallmark of cancer. To maintain genome integrity and support normal functions, cells have evolved an intricate network of DNA damage repair and cell-cycle checkpoint pathways, collectively known as the DNA Damage Response (DDR). DDR processes are consistently altered in cancer and loss of genome integrity plays a causal role in cancer development. However, this unique tumor biology and DDR deficiencies can be leveraged therapeutically to effectively kill cancer cells while sparing normal tissues. Pharmacological control of DDR processes might be used to block tumor growth directly by hindering cell division and induce apoptosis, or indirectly by unleashing the immune system against tumor cells. The latter could be achieved by engaging sensing mechanisms of aberrant DNA and RNA by the innate immune system, collectively studied as nucleic acid sensing (NAS). Moreover, in recent years, DDR/NAS processes have been described to play roles in age-related diseases other than cancer, including trinucleotide repeat expansion and auto-inflammatory syndromes. Pfizer scientists are eager to collaborate with leaders in the DDR/NAS space to develop novel, high-impact treatments for patients across therapeutic indications. Gaining control over DDR/NAS processes provides the opportunity to tackle high unmet medical needs from a differentiated angle improving the life of patients.

Pfizer is interested in partnering opportunities in the DNA Damage Response/Nucleic Acid Sensing space to discover novel, life-changing therapies for patients. These approaches can be (m)RNA-, small molecule-, or large molecule-based.

Specific areas of interest include:

  • Control of DDR/NAS processes to impact diseases other than cancer, e.g., inhibition of aberrant nucleic acid sensing mechanisms in auto-inflammatory or age-related diseases
  • Novel synthetic lethality and chemo-combo opportunities to treat HR-proficient cancer
  • Approaches that unleash the immune system against tumors
  • Modulation of NAS/innate immune pathways as adjuvants to optimize efficacy and durability of vaccine