Study design

This research was conducted as an integrative review, a methodological approach that allows for the simultaneous inclusion of diverse study designs—including experimental, non-experimental, and theoretical research—to provide a holistic understanding of the phenomenon [12]. The review followed the five stages established by the Whittemore and Knafl framework: 1) problem identification, 2) literature search, 3) data evaluation, 4) data analysis, and 5) presentation of results. This design is particularly appropriate for exploring bioethical challenges where empirical data must be synthesized with normative and philosophical perspectives.

Search strategy and information sources

A systematic search was performed across four electronic databases to ensure global and regional coverage: PubMed/MEDLINE, Scopus, SciELO (Scientific Electronic Library Online), and LILACS (Latin American and Caribbean Health Sciences Literature). The inclusion of SciELO and LILACS was essential to capture evidence specifically generated within and for the Latin American context. The search was limited to articles published between January 2015 and December 2025.

The search strategy employed a combination of Medical Subject Headings (MeSH), Health Sciences Descriptors (DeCS), and free-text keywords. The primary search string was: (“Targeted Therapy” OR “Precision Oncology” OR “Molecular Targeted Therapy”) AND (“Bioethics” OR “Ethics, Medical” OR “Health Equity” OR “Social Justice”) AND (“Latin America” OR “Developing Countries” OR “Low-Resource Settings”). Boolean operators (AND, OR) were used to optimize retrieval. No language restrictions were applied; however, the analysis focused on literature published in English, Spanish, and Portuguese.

Eligibility criteria

To maintain high scientific rigor, the following criteria were applied.

Exclusion criteria

• Purely clinical or pharmacological studies (e.g., drug efficacy reports or Phase I/II trials) without socio-ethical or economic discussion.

• Studies focused exclusively on conventional chemotherapy or radiotherapy.

• Editorials, conference abstracts, and gray literature without formal peer-review validation.

The search and selection process is summarized in Figure 1. A total of 298 records were identified through the database. Following removal of 8 duplicate records, 290 records were screened by title and abstract. Of these, 241 records were excluded as they did not address the intersection of targeted anti-tumor therapies, bioethics, and low-resource or Latin American contexts, or were published in languages other than English, Portuguese, or Spanish. The remaining 49 records were assessed for eligibility through full-text review. Of these, 25 were excluded for the following reasons: absence of a substantive bioethical dimension (n = 9), no specific relevance to Latin American or low- and middle-income country (LMIC) contexts (n = 11), or inaccessibility of full text (n = 5). A final total of 24 studies were included in the integrative synthesis.

Display full size

Figure 1. PRISMA-adapted flow diagram of the search and selection process. The diagram illustrates the identification, screening, eligibility assessment, and inclusion stages of the integrative review. Adapted from: [13]. © Author(s) 2021. Creative Commons CC BY 4.0 license.

A small number of studies conducted in non-Latin American LMICs—specifically India and sub-Saharan Africa—were included where their findings addressed structural barriers, FT mechanisms, or research ethics dilemmas with documented analogues in the Latin American context. The inclusion of these studies was based on the following considerations: 1) the shared structural condition of resource-constrained public healthcare systems with limited molecular diagnostics infrastructure; 2) the comparability of FT mechanisms and drug pricing barriers; and 3) the relevance of their ethical frameworks to the research vulnerability and PTA dilemmas identified in the Latin American literature. It is explicitly acknowledged that these non-Latin American LMIC populations differ from Latin American admixed populations in terms of genetic ancestry composition (Amerindian, African, and European lineages), pharmacogenetic profiles, and healthcare governance structures. Findings from these contexts were therefore incorporated as corroborating structural evidence rather than as direct biological or clinical equivalents, and the transferability of these findings to Latin American populations is acknowledged as a limitation of this review.

Data evaluation and quality appraisal

The quality of the included studies was appraised using the Mixed Methods Appraisal Tool (MMAT), version 2018 [14], which facilitates the evaluation of diverse methodologies through specific criteria. For theoretical and philosophical papers, appraisal focused on the clarity of the ethical argument and its contextual relevance to Latin America. As this is a single-author review, a two-stage screening process was implemented: the author conducted an initial selection based on titles and abstracts, followed by a second full-text review after a two-week interval to ensure intra-rater reliability and minimize selection bias.

Data analysis and synthesis

The findings were synthesized using thematic analysis [14, 15]. This process involved: 1) line-by-line coding of the results and discussions of primary studies, 2) grouping codes into descriptive themes, and 3) developing analytical themes that interpret the ethical challenges within the structural constraints of Latin American healthcare systems. This method allowed for the integration of quantitative data on access disparities with qualitative insights into the lived experiences of patients and clinicians.

Researcher reflexivity

As an integrative review that synthesizes qualitative, quantitative, and theoretical evidence on a value-laden topic, this study is subject to the interpretive influence of the researcher’s positionality. The author is a physician-researcher affiliated with institutions in Paraguay, an LMIC whose healthcare system embodies many of the structural constraints—limited public funding, restricted access to molecular diagnostics, and reliance on judicial mechanisms for access to high-cost drugs—analyzed in this review. This positionality confers a direct contextual understanding of the phenomenon under study and informed the selection of analytically relevant themes. At the same time, it carries the risk of confirmation bias, whereby evidence consistent with the author’s lived professional context may be weighted more heavily than contradictory evidence. To mitigate this risk, the thematic analysis was conducted following explicit coding procedures, the MMAT appraisal was applied using standardized criteria, and interpretive claims in the Discussion are framed with hedging language reflecting the available level of evidence. Readers are encouraged to interpret the findings with awareness of this positionality.

Study selection, characteristics and quality assessment

This integrative review included a diverse corpus of literature. The selection comprises original qualitative research, quantitative descriptive studies, mixed-methods designs, and theoretical analyses (Table 1). The evidence primarily originates from major Latin American hubs—including Brazil, Argentina, Mexico, Chile, and Colombia—while also incorporating data from other LMICs with high contextual applicability to the region. The included studies represent a multidisciplinary perspective, incorporating views from oncologists, bioethicists, patient advocacy groups, and health economists, thereby providing a holistic view of the targeted therapy implementation landscape. Theoretical articles were evaluated based on the robustness of their normative arguments, logical coherence, and regional relevance. Overall, the included literature demonstrated high scientific rigor, with approximately 80% of the studies meeting at least four out of five MMAT criteria.

Qualitative research successfully addressed the integration of data collection and findings, although a recurring gap was the lack of explicit reflexivity regarding the researcher’s influence, which is particularly sensitive when dealing with vulnerable cancer populations [14]. Quantitative descriptive studies showed strong sampling strategies, though many were limited by non-validated instruments adapted from HICs without prior cultural or linguistic pilot testing. Mixed-methods research exhibited the highest variability in reporting, especially regarding the explicit rationale for integrating qualitative and quantitative strands. Theoretical articles, while not empirically evaluated by MMAT, provided high-level conceptual justifications for applying principles of social justice and distributive ethics to the Latin American landscape, offering essential normative weight to the empirical findings.

The synthesis of the evidence revealed four major analytical themes that define the bioethical landscape of targeted therapies in Latin American low-resource settings [31].

The innovation paradox: FT and distributive justice

The primary bioethical dilemma identified is the innovation paradox, wherein scientific breakthroughs in precision oncology—designed to improve outcomes—become the very mechanism that exacerbates health inequities in the Global South. This theme explores how the market-driven nature of oncology innovation conflicts with the ethical requirement of universal health coverage.

Targeted therapies, including monoclonal antibodies, TKIs, and immune checkpoint inhibitors, represent a financial impossibility for most Latin American healthcare systems. Illustrative examples include trastuzumab and pertuzumab for HER2-positive breast cancer, osimertinib for EGFR-mutated non-small cell lung cancer (NSCLC), imatinib for BCR-ABL-positive chronic myeloid leukemia, and pembrolizumab for PD-L1-expressing solid tumors—agents whose annual costs routinely exceed the per-capita public health budget of most Latin American countries. Current pricing for many targeted agents exceeds an annual cost of 100,000 to 150,000 USD per patient [17, 18], a burden particularly acute in Latin America where these figures represent 10 to 20 times the annual GDP per capita of the region. These costs far exceed the per-patient oncology expenditure capacity of public healthcare systems [32], creating a structural barrier that effectively excludes the vast majority of the population [3].

Recent data suggest that while these drugs are theoretically available via regulatory approval, their real-world accessibility in public low-resource settings remains below 70%, with access to specific agents for rare molecular alterations (e.g., MET exon 14 skipping, ALK rearrangements, or NTRK fusions) being virtually zero in the public sector [19, 20]. This pricing model ignores the value-based context of the region, where the opportunity cost of funding one patient’s targeted therapy might equal the screening budget for an entire municipality.

The review identifies FT not merely as an economic side effect but as a critical determinant of clinical outcomes and a violation of the principle of non-maleficence. FT forces patients into catastrophic health expenditure, leading to the depletion of family assets, the sale of homes, and the adoption of dangerous coping strategies such as dose-rationing or treatment delay [21].

Quantitative findings highlight that in some LMIC settings, up to 62.5% of patients discontinue targeted therapies prematurely due to cost [22]. This treatment abandonment leads to a biological penalty, where the survival advantage offered by the therapy is lost. For instance, in aggressive malignancies like glioblastoma, median survival can plummet to as low as 7.6 months when supportive and targeted care is inaccessible [22]. Ethically, this situation constitutes structural harm, as the system offers a promise of life that the economic reality subsequently rescinds, resulting in social and economic ruin for the survivor’s family [11, 23].

The evidence underscores a profound public-private dichotomy, manifesting as the “Inverse Care Law”: the availability of high-quality precision oncology is inversely proportional to the medical need of the population [4]. In countries like Brazil and Mexico, the private sector offers molecular profiling and targeted agents comparable to HICs, while public sector patients face therapeutic nihilism—a state where physicians stop discussing innovative options because they know they are unavailable [2]. This disparity creates ethical distress among oncology professionals who navigate the chasm between what is clinically indicated by international guidelines and what is locally possible, often leading to burnout and moral injury [21, 24].

Infrastructure deficits and epistemic injustice

The implementation of targeted therapies is stymied by secondary barriers related to diagnostic infrastructure. This creates a state of diagnostic abandonment and perpetuates a form of systemic exclusion known as epistemic injustice.

A critical finding is the extreme scarcity of next-generation sequencing (NGS) capabilities in the public sector. Evidence suggested that NGS access in LMIC oncology centers remained critically limited, with available data indicating rates as low as 9.4% [22], a finding consistent with documented barriers to molecular diagnostics infrastructure across low-resource settings, including limited laboratory capacity, absence of bioinformatics expertise, and prohibitive sequencing costs [5]. Without local NGS profiling, actionable alterations such as EGFR exon 19 deletions, ALK rearrangements, BRAF V600E mutations, NTRK fusions, and MET exon 14 skipping mutations—each with a corresponding approved targeted agent—remain undetected, effectively rendering precision oncology inaccessible regardless of drug availability. This deficit forces reliance on central laboratories abroad or high-cost private labs, introducing logistical delays and a diagnostic odyssey that compromise the window of opportunity for initiating therapy in aggressive malignancies [16, 19]. Furthermore, the lack of cold chain logistics for sample transport often results in degraded biological material, further marginalizing patients in rural areas who are technically eligible but logistically excluded.

The review identifies a profound epistemic injustice rooted in the Eurocentric bias of global genomic databases. Approximately 80% of participants in genomic studies are of European ancestry, which differs significantly from the admixed Latin American populations [6, 7]. This lack of representation means that molecular drivers and somatic mutation profiles in Latin American patients are poorly characterized. This representational injustice can lead to the omission of relevant regional targets or the application of ineffective agents [25]. Ethically, this means that Latin American patients are being treated with proxy data that may not reflect their actual biological reality.

Applying HIC-centric guidelines to Latin American patients carries the risk of unexpected toxicities. Variations in pharmacokinetics and pharmacodynamics (PK/PD) due to ancestral genetic diversity (e.g., variants in CYP450 enzymes specific to Amerindian or African lineages) remain unstudied locally [26]. The principle of non-maleficence is threatened when physicians borrow clinical data from foreign populations, potentially leading to adverse drug reactions or therapeutic failure [25, 26]. There is an urgent ethical imperative to fund local genomic research not as a luxury but as a prerequisite for safe and effective clinical practice.

Vulnerability in clinical research and informed consent

Structural vulnerabilities in Latin America compromise the pillars of autonomy and justice, turning clinical research into a contested ethical space. Evidence suggests that for many Latin American patients, trial enrollment is a desperation-driven strategy. In contexts where targeted therapies are not funded, trials represent the only access point to innovation [8, 33]. This phenomenon is particularly acute in trials investigating agents such as tepotinib (MET exon 14), selpercatinib (RET fusions), or entrectinib (NTRK fusions), where no publicly funded alternative exists in most Latin American healthcare systems. This therapeutic misconception—where the boundary between research and care is blurred—creates a profound power imbalance. Vulnerable subjects may downplay risks or ignore side effects due to the fear of being removed from a trial that is their only “salvavidas” (lifesaver), raising questions about the true voluntariness of consent and the potential for exploitation [1].

Precision oncology introduces concepts (e.g., germline vs. somatic mutations, probability of response, incidental findings) that exceed the health literacy level of many regional populations. Consent forms often exceed the average patient’s reading ability, being written at a postgraduate level [27, 28]. This literacy gap is acute in indigenous communities where linguistic and cultural differences regarding the concepts of “inheritance” and “illness” prevail. Failure to adapt these forms violates the principle of respect for individuals and turns consent into a bureaucratic signature rather than an autonomous decision [29].

A major ethical conflict identified is the lack of PTA. Responding patients frequently lose access to successful therapies once a trial concludes if the drug lacks local public funding [8, 33]. This constitutes a form of data extraction or biopiracy where the Global South provides the subjects for global approvals, but the participants are denied the long-term benefits of the research. Regional frameworks increasingly advocate for pre-negotiated PTA agreements as a non-negotiable requirement for research approval [33].

The judicialization dilemma: individual rights vs. systemic sustainability

Medical judicialization—using court orders to compel the state to provide high-cost drugs—challenges the foundations of public health ethics and the principle of equity. The review highlights a tension between the subjective “right to health” (interpreted as the right to any available technology) and the principle of distributive justice. In countries like Brazil and Colombia, judicialization has become a backdoor for high-cost targeted therapies, often bypassing health technology assessments [10]. While court orders fulfill the individual’s claim to life, they frequently ignore the evidence-based prioritization needed to sustain a public system, essentially individualizing a social and political problem [30].

A critical finding is that judicialization frequently exacerbates inequities. Litigants are predominantly individuals with higher educational and socioeconomic levels who possess the legal capital to sue the state [10]. This creates a “Robin Hood” effect in reverse: limited public funds are diverted to cover expensive targeted agents for a few, frequently at the expense of primary oncological services (e.g., HPV vaccination or basic screening) that would benefit the more vulnerable, non-litigating majority [11].

The scale of judicialization threatens systemic non-maleficence. The financial strain can lead to institutional bankruptcy, where the state cuts funding for basic medical supplies to comply with court mandates for a single high-cost drug [30]. This creates a zero-sum game where the benefit to one patient results in harm to the broader population by destabilizing the healthcare infrastructure [11].

Table 2 provides a structured overview of the four analytical themes identified in this integrative synthesis, summarizing key findings, bioethical principles implicated, representative clinical examples, and derived policy implications.