From:  Bioethical challenges in the implementation of targeted anti-tumor therapies in low-resource settings: a perspective from Latin America

 Structured overview of analytical themes identified in the integrative synthesis.

Analytical themeKey findingsBioethical principles implicatedRepresentative examplesPolicy implications
1. Innovation paradox and financial toxicityTargeted therapy costs exceed 100,000–150,000 USD/year, representing 10–20× the regional GDP per capita; up to 62.5% of patients discontinue treatment prematurely due to cost; financial toxicity leads to catastrophic health expenditure, dose-rationing, and treatment abandonmentDistributive justice; non-maleficence; right to healthTrastuzumab, pertuzumab (HER2+ breast cancer); osimertinib (EGFR+ NSCLC); pembrolizumab (PD-L1+ solid tumors); imatinib (CML)Tiered pricing models reflecting regional purchasing power; ESMO-MCBS-based prioritization; regional price negotiation treating Latin America as a unified economic bloc
2. Infrastructure deficits and epistemic injusticeNGS available in as few as 9.4% of LMIC oncology centers; ~80% of genomic study participants are of European ancestry; admixed Latin American populations (Amerindian, African, European lineages) underrepresented in molecular databases; unstudied CYP450 variants risk unexpected toxicitiesNon-maleficence; epistemic justice; scientific integrityEGFR, ALK, BRAF, NTRK, MET exon 14, RET alterations undetected without local NGS; Eurocentric genomic databases misrepresent regional mutation profilesGenomic sovereignty: development of regional reference databases; public investment in local NGS infrastructure; protection of Latin American genomic data from extractive research practices
3. Research vulnerability and informed consentClinical trials function as survival strategies for patients lacking funded alternatives; therapeutic misconception compromises voluntariness of consent; consent forms written at post-graduate reading level; lack of PTA agreements constitutes biopiracyAutonomy; justice; respect for persons; non-exploitationTrials of tepotinib (MET exon 14), selpercatinib (RET fusions), entrectinib (NTRK fusions) with no publicly funded alternative; consent literacy gaps in indigenous communities regarding concepts of inheritance and illnessMandatory pre-negotiated PTA agreements as condition for research approval; culturally adapted consent through community health mediators and dialogic consent processes; ethics committee reform toward active advocacy
4. Judicialization dilemmaCourt-ordered access to high-cost drugs bypasses health technology assessment; litigants are predominantly higher socioeconomic status individuals with legal capital; reverse Robin Hood effect diverts public funds from primary oncology services; institutional bankruptcy riskJustice; equity; non-maleficence at population level; sustainabilityJudicialization of trastuzumab, bevacizumab, and checkpoint inhibitors in Brazil and Colombia; diversion of funds from HPV vaccination and basic screening programsFrugal precision oncology paradigm; strengthening of HTA processes incorporating ethical values; legal frameworks distinguishing individual rights from systemic equity obligations

CML: chronic myeloid leukemia; ESMO-MCBS: European Society for Medical Oncology Magnitude of Clinical Benefit Scale; HTA: health technology assessment; LMIC: low- and middle-income country; NGS: next-generation sequencing; NSCLC: non-small cell lung cancer; PTA: post-trial access.