Every patient

Abstract

Cancer research is grounded in the mission to improve the lives of patients with cancer – every patient. Decades of basic cancer research have led to remarkable treatment breakthroughs that have yielded major responses in patients with a variety of cancers, but not all sections of society have benefitted equally from these advances. Cancer health disparities continue to persist between high- and low-income countries, as well as rural communities as compared to those living in urban environments. American Indians/Alaska Natives, American Asians, and Hispanics have higher incidence of liver cancer compared to other populations, while African Americans have the highest death rates from cancers of the breast, gastrointestinal tract, lung, and prostate [1.Minas T.Z. et al.An overview of cancer health disparities: New approaches and insights and why they matter.Carcinogenesis. 2021; 42: 2-13Google Scholar]. Meanwhile, sexual and gender minorities are at an increased risk of cancer relative to heterosexuals [2.Khan M.A. et al.Looking at cancer health disparities without the colored lenses.Cancer Health Disparities. 2019; 3: e1-e9Google Scholar]. Therefore, factors underlying health equity need to be embedded in all facets of cancer research and care to reduce cancer disparities. Researchers and clinicians have since moved away from a ‘one size fits all’ treatment approach, to a more personalized approach, which has the potential to dramatically reduce cancer health disparities. If successful, precision oncology would ensure that the right care is delivered to the right patient at the right time. However, many racial and ethnic minorities are significantly under-represented in cancer research and clinical trials, and do not receive equal benefits in clinical practice. Our understanding of tumor biology, cancer risk, and treatment response has largely been derived from patients of European descent. This underrepresentation exacerbates cancer health disparities and prevents equitable precision cancer medicine treatments. This special issue of Trends in Cancer examines the factors that underpin cancer health disparities in racial and ethnic minorities and other underserved populations. As multiple types of determinants, including biological/genetic, environmental, behavioral, health care, and social determinants contribute to individual cancer risk and survival after a cancer diagnosis, we hope that these articles showcase a paradigm for how collaboration between basic biomedical researchers, clinicians, and public health researchers can not only uncover unique vulnerabilities in cancer, but provide ways for researchers to implement, integrate, and communicate their findings to the public. If the pandemic has taught us anything, it is that science can only take us so far. If scientists cannot gain the trust of the public they serve, we will still have not won the war on cancer. Many studies have revealed differences in the biological and clinical characteristics of certain cancers when looking at tumors derived from racial and ethnic minorities, suggesting a rationale for why particular treatments are not effective for all populations. Several reviews in this special issue examine these mechanistic differences in tumor biology. Stefan Ambs and colleagues review how differences in inflammation and immune responses among population groups can contribute to cancer disparities. Nicholas Pannunzio and colleagues discuss the links between double-strand break repair and health disparities in blood cancer. Lichun Ma and Xin Wei Wang use liver cancer disparities as a paradigm to argue that understanding tumor heterogeneity and identifying shared common features of cancer in diverse populations can reduce inequities. In addition to race, sex and gender contribute to disparities in cancer development and outcome. Joshua Rubin details the mechanisms underlying cancer disparities between male and female. Among these mechanisms is the role of sex hormones in cancer progression. As hormone replacement therapy is gaining prevalence in transgender communities, Alison Berner and colleagues argue for the need to include transgender patients in scientific research to better understand the biological role of sex hormones in cancer and to reduce disparities within the transgender community. Given the significant differences in tumor biology and response to treatment that can be observed across populations, more emphasis is needed on the development of diverse sets of cancer models so that we do not generalize results based on information gained from cohorts with little or no diversity. Unfortunately, only 19% of genome-wide association studies (GWAS) are in samples from underrepresented populations [3.Popejoy A.B. Fullerton S.M. Genomics is failing on diversity.Nature. 2016; 538: 161-164Google Scholar], thereby limiting meaningful conclusions to be drawn from ethnic and minority groups. In addition, racial and ethnic categories used to define minority populations are often oversimplified and can further complicate associations. For example, data from Latinos/Hispanics are often aggregated together despite representing a highly diverse group of individuals with Mexican, Cuban, Puerto Rican, Central, or South American ancestry. Moreover, genetic admixture, or the presence of multiple genetic backgrounds, has become more prevalent over time. Recent initiatives like the multi-institutional initiative, Polyethnic-1000 (P-1000) proposed by Nicolas Robine and Harold Varmus is making it a priority to enhance our understanding of inherited genetic diversity in cancer by collecting tumor samples from a range of diverse ancestries. Moreover, many scientists are creating a pool of patient derived models that better represent the patient populations most vulnerable to cancers. Nicole Halmai and Luis Carvajal-Carmona argue that preclinical xenograft and organoid minority-patient models can be used to identify distinct mechanisms of treatment response and resistance in minority patients. Regardless of scientific advances, cancer disparities will persist if disadvantaged communities continue to lack resources that allow them to protect and enhance their well-being. Indeed, genetic factors have so far only been found to minimally contribute to cancer disparities. Instead, cancer health disparities are often the result of the social and economic conditions in which a patient lives, learns, works, plays, and ages. Recognizing the critical role that these social determinants of health play in promoting health disparities is pivotal to reducing inequities. Melissa Davis and colleagues argue that biological and social determinants of health should work in concert to mitigate cancer health disparities. Being able to differentiate between the biological differences that arise from genetic ancestry versus those of the external environment will help to determine how social determinants of health impact on cancer progression and treatment response. Most inequities in wealth, education, and overall standard of living among racial and ethnic minorities stem from historical and persistent structural racism and discriminatory practices. As a result, many of these populations live in surroundings that lack quality medical care, housing, and food, which adversely affect their health and cancer outcome. For example, people from socioeconomically disadvantaged groups often reside in surroundings with high levels of air pollution and ground water with carcinogenic contaminants, which are known to increase cancer risk and impact on a person’s biology. Rosalind Wright and Heidi Hanson suggest that understanding how exposures from a person’s environment, diet, and lifestyle interact with a person’s own genetics, physiology, and epigenetics to impact on their health, known as exposomics, could provide more opportunities to reduce cancer burdens in socioeconomically disadvantaged and minoritized communities. The environmental, social, and cultural variables that modulate risk also need to be integrated with known predictors of cancer to ensure that underserved populations receive the most effective interventions in an environment that they trust. Philip Castle and colleagues discuss how precision cancer prevention practices should include social determinants of health to advance health equity. Even when research and clinical trials are inclusive, the growing costs associated with cancer care, especially seen in the US, can place an insurmountable burden on patients and families, causing many to abandon treatment. Yousuf Zafar and Fumiko Chino discuss how financial toxicity can create further divides among disparate groups. Each of the articles presented in this issue underscore the value of trust between researchers and the public to reduce disparities. One way to gain trust is to grow a diverse and inclusive scientific community. It is well known, even if not yet successfully implemented, that diversity can foster scientific creativity and innovation as well as promote trust in underserved communities [4.No authors. Diversity and inclusion in cancer research and oncology.Trends Cancer. 2020; 6: 719-723Google Scholar]. George Weiner and Robert Winn also argue that community engagement and outreach is critical to gaining trust in science. Researchers should be encouraged to tailor their research programs to the needs of the communities they serve, and patients should be actively engaged in the inception of research studies. Several authors also describe how advocates can help bridge the gap between researchers and patients by communicating the patient perspective to researchers. Precision medicine will only succeed if every patient with cancer is properly diagnosed and treated. This success relies on addressing the factors that drive disparities in marginalized groups and ensuring that the efforts are applied to and utilized by those who need it. I hope that the articles in this issue underscore that biomedical science cannot achieve this goal alone. Researchers and clinicians need to expand their collaborations to incorporate the voices of patients and advocates from underrepresented groups as well as sociological perspectives. We at Trends in Cancer also acknowledge that this special issue only begins to scratch the surface of cancer disparities research, and we will continue raising awareness of this topic in future issues. We thank the authors and referees for working to very tight deadlines to compile this special issue. It has been a great pleasure for me to develop the ideas for this special issue, and I hope you also enjoy stepping outside your own particular discipline to read some of these articles. We believe your colleagues from other departments will enjoy reading them too, and we welcome your feedback at [email protected] or @trendscancer.