Precision oncology is revolutionizing cancer treatment by tailoring medical care based on the genetic makeup of a patient’s tumor. However, significant disparities exist in the effectiveness and availability of these treatments among patients of different ancestries. This article delves into the root causes of these disparities and their impact on cancer outcomes.
The Rise of Precision Oncology
Precision oncology has emerged as a promising field, with nearly half of all new cancer drugs approved by the U.S. Food and Drug Administration (FDA) in the past 25 years targeting specific genetic changes responsible for tumor growth. By analyzing genetic mutations in tumors, oncologists can match patients with targeted therapies, many of which have become standard treatment options and continue to be evaluated in clinical trials. Despite these significant advancements, not all patients are equally able to benefit from this cutting-edge technology.
Targeted Cancer Treatments
The basis of precision oncology lies in its ability to identify specific genetic mutations in a tumor and tailor treatments to target those mutations effectively. This approach contrasts sharply with traditional cancer treatments, which often employ broad-spectrum methods that can affect healthy as well as cancerous cells. Precision oncology’s targeted approach aims to minimize harmful side effects while maximizing the treatment’s efficacy. As these personalized treatments become more prevalent, they hold the potential to transform cancer care, offering patients a higher quality of life alongside improved survival rates. Oncologists utilize a range of advanced diagnostic tools, including next-generation sequencing and liquid biopsies, to identify actionable mutations and match them with the most appropriate therapies.
Historical Representation in Clinical Trials
Despite the groundbreaking nature of precision oncology, a significant disparity exists in who benefits from these treatments. Research conducted by Memorial Sloan Kettering Cancer Center (MSK) has shown that patients of European ancestry have a greater likelihood of being matched with the latest precision oncology therapies compared to patients of non-European ancestries. This inequity is deeply rooted in the historical representation of genetic data in clinical trials and research studies. Over the years, a disproportionate number of DNA samples from individuals of European ancestry have been used in genetic research. Consequently, the data pool has favored the discovery of biomarkers and the development of drugs that are more effective for European-descended individuals.
Genetic Differences and Ancestry
Defining Ancestry in Genetic Research
In genetic research, the term “ancestry” refers to the genetic origin and biology of individuals, which is distinct from the physical characteristics of race or the cultural identification of ethnicity. This distinction is crucial in understanding how genetic differences can influence the efficacy of cancer treatments. Over 80% of DNA samples used in pooled data sets from academic medical centers and large-scale projects such as The Cancer Genome Atlas (TCGA) and AACR Project GENIE come from self-reported white patients of European ancestry. This overrepresentation is not merely a statistical quirk but reflects a historical trend where European-descended individuals were more likely to participate in clinical trials.
Impact of Overrepresentation
The overrepresentation of European-descended individuals in clinical trials has led to a skewed understanding of genetic biomarkers and consequently, the development of precision oncology drugs. Since the discovery process has been primarily based on data from European ancestry patients, these drugs are most effective for that demographic. Patients with European genetic backgrounds have a higher likelihood of receiving targeted cancer treatments, which translates to better outcomes for this group. Conversely, this imbalance leaves patients of non-European ancestries at a disadvantage, both in terms of access to effective treatments and the likelihood of positive outcomes.
Analyzing Disparities in Treatment
MSK-IMPACT Study Findings
The MSK-IMPACT study provides critical insights into the disparities in precision oncology treatments between different ancestries. By analyzing data from 59,433 patients whose tumors were examined using MSK-IMPACT, a test that identifies mutations in 505 cancer-related genes, the researchers could assess the representation of various ancestries. Genetic analysis, focusing on single nucleotide polymorphisms (SNPs), was used to determine each patient’s ancestry and categorize them accordingly. Approximately three-quarters of the patients analyzed were of European ancestry, while the remaining included smaller percentages of East Asian, South Asian, and African ancestry. Patients of mixed ancestry, comprising about 11% of the samples, were excluded due to the genetic complexity of mixed backgrounds.
Likelihood of Receiving Targeted Drugs
The team investigated the likelihood of patients from different ancestries being matched with FDA-approved precision oncology drugs over a 25-year period, from 1998 to 2023. During this time, the number of biomarker-based drug approvals increased significantly, furthering the advancement of personalized cancer treatments. However, the findings revealed substantial disparities in access to these treatments. Patients of European ancestry saw a 9.1-fold increase in receiving personalized drugs, while patients of East Asian ancestry experienced an 8.5-fold increase. In contrast, patients of South Asian ancestry had a 6.8-fold increase, and those of African ancestry had only a 6-fold increase. These disparities underscore the urgent need to include a more diverse patient population in genetic research and clinical trials to ensure equitable access to life-saving treatments.
Specific Disparities in Cancer Treatments
Lung Cancer and EGFR Mutations
Lung cancer treatments highlight the importance of understanding genetic differences among ancestries. Drugs targeting EGFR mutations have been found to be particularly beneficial for East and South Asian ancestry patients, who are more likely to carry these mutations. EGFR mutations are a critical driver of tumor growth and their prevalence varies significantly by ancestry. In East and South Asian populations, a higher percentage of lung cancer patients exhibit EGFR mutations, making targeted therapies more effective for these groups. These findings highlight the necessity for developing treatments that take into account the genetic makeup of different populations.
Immune Checkpoint Inhibitors
Immune checkpoint inhibitors, such as pembrolizumab (Keytruda), represent another area where disparities exist. These drugs are more commonly prescribed to patients of European ancestry due to the higher prevalence of the high tumor mutation burden (TMB-H) molecular signature in this group. The TMB-H signature is an indicator of how many mutations a tumor carries, and a high mutation load can make tumors more visible to the immune system, thereby enhancing the effectiveness of immune checkpoint inhibitors. This disparity underscores the need for more inclusive research practices that can identify and validate biomarkers relevant to diverse populations, enabling equitable access to these advanced treatments.
KRAS-G12C Mutation Drugs
The effectiveness of newer drugs targeting the KRAS-G12C mutation in lung and colorectal cancers also varies among ancestries. These drugs have been less effective for patients of African ancestry with colorectal cancer, who are more likely to carry different KRAS mutations. The KRAS gene plays a significant role in cell signaling pathways that impact cell growth and division. Therefore, variations in KRAS mutations can affect the efficacy of targeted therapies. This finding underscores the necessity of diversifying clinical trial participants to ensure that new treatments are effective across all genetic backgrounds. Efforts to develop more inclusive research practices are critical for advancing cancer care and reducing disparities in treatment outcomes.
Addressing Disparities in Cancer Outcomes
Importance of Diverse Genetic Data
Understanding genetic differences is essential to closing the gap in cancer outcomes among different ancestries. Addressing these disparities requires concerted efforts to improve access to clinical trials and healthcare for patients of lower socioeconomic status. By fostering inclusive research practices, the medical community can ensure that discoveries and treatments are representative of the diverse populations they are intended to serve. This includes increasing the participation of underrepresented groups in genetic research to develop targeted therapies that are effective for all patients, regardless of their genetic background.
Increasing Diversity in Clinical Trials
Precision oncology is transforming cancer treatment by personalizing medical care based on the unique genetic profile of a patient’s tumor. This approach allows for more targeted and effective treatment strategies. However, there are major disparities in how successful and accessible these treatments are for patients from different ethnic backgrounds. This article explores the underlying reasons for these disparities, including genetic diversity, socioeconomic factors, and healthcare access. It also examines how these differences affect cancer outcomes for various populations. By understanding and addressing the root causes of these disparities, the medical community can work towards more equitable cancer treatment that benefits all patients, regardless of their ancestry. This insight is crucial as it aims to bridge the gap in healthcare and ensure that advanced treatments in precision oncology are available to everyone, ultimately improving cancer outcomes across the board.
