It would be difficult for any objective observer of the current cancer management paradigm to suggest that precision medicine is not playing an important role in defining optimal therapeutic strategies for individual patients. Further, it is virtually certain that cancer drug development in the future will have a continued focus on obtaining detailed molecular data from the tumor/germline to assign specific treatments. Finally, it is highly likely that precision medicine will increasingly affect other aspects of cancer management, including the recommendation to employ specific prevention and screening strategies, or receive/avoid specific drugs based on germline profiles (pharmacogenomics).
However, in the opinion of this commentator, there are aspects of the growth of precision cancer (“molecular”) medicine, two of which are highlighted here, that raise concerns deserving of additional discussion as this revolution in management moves forward.
The first question relates to the societal value of the specific focus of precision medicine on the biological and pathological effects of molecular abnormalities within the tumor/germline of individuals with or at risk of developing cancer vs an alternative far more global public health perspective on reducing the burden of malignant disease.
Clearly, this issue has multiple components, including the priority given to research funding and to the level of financial support provided at the federal, state, and local levels to public health strategies for cancer prevention and early detection.
Although one can certainly make the argument that there should be no irreconcilable conflict between the goals of molecular-based and population-based approaches to cancer control, an objective assessment of both the current health and cancer care landscapes would provide a strong dissent to this conclusion, with the realistic requirement for society to thoughtfully prioritize both limited financial and personnel resources.
In addition, one might reasonably suggest that as a greater proportion of cancer-associated health care dollars is allocated to expensive precision medicine therapeutic strategies, there will likely be less available for public/ population-based approaches more focused on prevention. One can only imagine, for example, the financial burden on third-party payment (including government sources) associated with such novel approaches as CRISPR-based personalized antineoplastic agents.1
The thoughtful but provocative words of James Tabery, author of the recently published book Tyranny of the Gene: Personalized Medicine and Its Threat to Public Health, emphasize a perspective worthy of additional discussion2:
“My thesis is that there have been and remain powerful financial, political, technological, and scientific forces that are driving this embrace of personalized medicine and promoting the idea of medicine as something genetic while simultaneously impeding the study of environmental determinants of wellness and disease. Genes have become far easier to study than environments. Probing DNA has benefitted from technical developments that have eluded environmental health research, and medical genetic research has been subject to less partisan politicization than environmental health research. The result of all this is a biomedical research industry that is now prioritizing the study of genetic causes of health and illness not because those causes play a particularly large role in health outcomes but because those causes are faster, cheaper, more profitable, and more politically palatable than the environmental alternative.”
Importantly, others have reached similar conclusions regarding the status and complexities of critically relevant public health initiatives in this country.3 Societal support for such strategies, including continued efforts to reduce all forms of tobacco use, human papillomavirus vaccination, demonstrated effective cancer screenings, and obesity management, simply cannot be overstated.
In summary, caution is advised that the situation highlighted above not become a competition, but rather effective complementary approaches to the cancer problem and that essential public health strategies never become a casualty of the precision medicine revolution. There is much to consider, and further discussion is warranted.
Returning to the demonstrated remarkable success of precision cancer medicine in favorably affecting the survival of individual patients with advanced cancers, we observe a different but equally perplexing issue: that of the observed less than optimal utilization of essential molecular diagnostics (including next-generation sequencing [NGS]) in noninvestigative clinical practice.
Consider for a moment the realistic potential for widespread standard-of- care utilization of NGS testing in routine oncology care, as demonstrated in a recent report of a health organization “pathologist-directed protocol system-wide [platform], where somatic testing was performed immediately at the time of diagnosis for all patients with advanced solid tumor[s].”4
Approximately half of all patients in this analysis were found to have had “at least one actionable genomic biomarker-driven–approved and/or guideline-recommended targeted or immunotherapy,” with a similar percentage being potentially eligible for a molecular-based clinical trial. Further, for those individuals with at least 6 months of follow-up, 52% had been treated with either immunotherapy or a targeted therapeutic. Finally, while recognizing the critical fact that this was a heterogeneous population and the data were not generated from a randomized trial, individuals treated with a molecularly based targeted therapeutic experienced improved overall survival (P < .001) compared with those managed with chemotherapy alone. However, it must be noted that in this experience, “testing was also performed under the research protocol at no cost, to remove potential reimbursement-related barriers….”
So, the critical question to be asked here is: How many of the individuals able to benefit from the results of the molecular analysis would have been denied this opportunity if the required third-party payment for NGS testing had been denied or was insufficient for the procedure to be undertaken?
There are a number of reasons for the failure of clinicians to obtain somatic and germline molecular testing despite strong evidence of its clinical utility,5,6 including the absence of adequate decision-support tools, and concern for payment of these relatively expensive tests must surely be high on the list of physician concerns. The potential tragedy associated with the failure to identify a clinically relevant molecular abnormality that may result in effective treatment with the increasing number of regulatory-approved tumor-agnostic antineoplastic therapeutics is a concern that cannot be overstated.7
References
- Ledford H. CRISPR cancer trial success paves the way for personalized treatments. Nature. 2022;611(7936):433-434. doi:10.1038/d41586-022-03676-7
- Tabery J. Tyranny of the Gene: Personalized Medicine and Its Threat to Public Health. Alfred A. Knopf; 2023.
- Fineberg HV. Setting public health priorities in the United States. JAMA. 2025;333(12):1025-1027.doi:10.1001/jama.2025.0485
- Dowdell AK, Meng RC, Vita A, et al. Widespread adoption of precision anticancer therapies after implementation of pathologist-directed comprehensive genomic profiling across a large US health
system. JCO Oncol Pract. 2024;20(11):1523-1532. doi:10.1200/OP.24.00226 - Hage Chehade C, Jo Y, Gebrael G, et al. Trends and disparities in next-generation sequencing in metastatic prostate and urothelial cancers. JAMA Netw Open. 2024;7(7):e2423186. doi:10.1001/
jamanetworkopen.2024.23186 - Klatte DCF, Starr JS, Clift KE, et al. Utilization and outcomes of multigene panel testing in patients with pancreatic ductal adenocarcinoma. JCO Oncol Pract.2024;20(8):1081-1090. doi:10.1200/23.00447
- Gouda MA, Nelson BE, Buschhorn L, Wahida A, Subbiah V. Tumor-agnostic precision medicine from the AACR GENIE database: clinical implications. Clin Cancer Res. 2023;29(15):2753-2760.doi:10.1158/1078-0432.CCR-23-0090