Pharmacogenomic tests of oncology drugs at Instituto Nacional de Câncer (INCA)

ABSTRACT

The implementation, current status and future perspectives of the pharmacogenetics/genomics (PGx) testing program developed at Instituto Nacional de Cancer (INCA) are presented. Initial selection of drug-gene pairs for PGx testing was based on clinically-validated PGx associations and availability of international guidelines with PGx-informed dosing recommendations. The selected pairs were fluoropyrimidines- DPYD, irinotecan- UGT1A1, and thiopurines- TPMT/NUDT15. The aims and rationale for the implemented PGx tests, frequency of the interrogated genetic variants and assigned metabolic phenotypes, and the individual dosing recommendations are reviewed. Planned developments, such as collaboration with other cancer treatment centers, testing of additional drug-gene pairs (e.g., tamoxifen- CYP2D6 ), and inclusion of PGx testing in the routine workout of targeted patients at INCA were impacted by the outbreak of the COVID-19 pandemics. The Brazilian Society of Clinical Oncology is invited to play a leading role in the evaluation of the clinical utility of PGx tests of germline variants for oncology drugs in Brazil.

RESUMO

É apresentada a implementação, o estado atual e as perspectivas futuras do programa de testes farmacogenéticos/genômicos (PGx) desenvolvido no Instituto Nacional de Câncer (INCA). A seleção inicial de pares de genes-medicamentos para testes PGx foi baseada em associações PGx clinicamente validadas e disponibilidade de diretrizes internacionais com recomendações de dosagem segundo as características PGx individuais. Os pares selecionados foram fluoropirimidinas- DPYD, irinotecano- UGT1A1 e tiopurinas- TPMT/NUDT15. Os objetivos e a justificativa para os testes PGx implementados, a frequência das variantes genéticas interrogadas e dos fenótipos metabólicos atribuídos, e as recomendações de dosagem individuais são apresentados. Desenvolvimentos planejados, como colaboração com outros centros de tratamento de câncer, testes adicionais de pares de medicamentos-genes (por exemplo, tamoxifeno- CYP2D6 ) e inclusão de testes de PGx na rotina de pacientes-alvo no INCA foram impactados pela pandemia COVID-19. A Sociedade Brasileira de Oncologia Clínica é convidada a desempenhar um papel de liderança na avaliação da utilidade clínica dos testes PGx de variantes germinativas para medicamentos oncológicos no Brasil.

Keywords:

DPYD - Fluoropyrimidines - Irinotecan - NUDT15 - Pharmacogenomics - Thiopurines - TPMT - UGT1A1.

Descritores:

DPYD - Fluoropirimidinas - Irinotecan - NUDT15 - Farmacogenômica - Tiopurinas - TPMT - UGT1A1.

CONFLICTS OF INTEREST None to declare.

Financial support: none to declare.

Clinical trials : Not Applicable

Publication History

Received: 09 December 2020

Accepted: 19 December 2020

Article published online:
14 May 2021

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