Preclinical drug-testing to evaluate PARP inhibitors for infants with acute lymphoblastic leukaemia

Dr Rishi Kotecha from Telethon Kids' Institute is researching novel drug combinations for the treatment of ALL.
Dr Rishi Kotecha from Telethon Kids' Institute is researching novel drug combinations for the treatment of ALL.

Recipient: Dr Rishi Kotecha
Institute: Telethon Kids' Institute
Funding: $143,908 July 2021 to December 2022
Perpetual Funding: $120,000

Present therapy for childhood acute lymphoblastic leukaemia (ALL) has a cure rate of over 90%. However, not all types of leukaemia have benefited to the same extent from medical advances. Survival for high-risk infants, who are less than one year of age at the time of diagnosis, is still less than 50%, with poor quality of life in survivors due to treatment-related toxicities. Better therapies are desperately needed.

Acute lymphoblastic leukaemia in infants (iALL) has significantly inferior outcomes compared to older children, where the 5-year overall survival exceeds 90%. Patients are treated with up to ten chemotherapeutic drugs, yet more intensified therapy does not improve outcomes due to an increase in toxic death. Novel therapies are desperately needed.

There has been preclinical evidence of PARP inhibitor (PARPi) activity in acute myeloid leukaemia leading to development of several clinical trials. From laboratory testing we have discovered effective novel drugs, which are not currently used to treat babies with leukaemia. We will evaluate novel drug combinations and test them in model systems, such that they can be fast-tracked to the clinic to improve survival and quality of life.