Cancer Research Training Program Research Articles

Abstract B108: Developing and implementing an effective reflective practice toolkit on a cancer research training program

Abstract Hispanic/Latinos, Black/African Americans, Asians, American Indian or Alaska Natives, Native Hawaiians or Other Pacific Islanders, or individuals who report more than one race are underrepresented in the biomedical workforce. In order to combat this disparity, the Summer Cancer Research Institute (SCRI) was developed to train underrepresented minority (URM) students in cancer research. This study explored the feasibility and impact of reflective practices on trainees’ experience and learning outcomes within the SCRI training program. Reflective practice has been shown to increase metacognition, competency, feelings of belonging, and the sense of a scientific identity, all of which are crucial skills for URM trainees. In this study, we developed and implemented a robust toolkit to support reflective practice, which includes (1) four reflective journal entries, (2) four bi-weekly check-in discussion groups, (3) two social media posts, (4) two reflective practice seminars and (5) pre- and post-program surveys. The toolkit was utilized to actively engage trainees in reflective practices throughout their participation in the summer training program. The goals were to (1) enhance the trainees' ability to effectively use reflective practice for their learning, and (2) support and improve their overall learning experience and outcomes in the summer training program. Grounded theory was used to analyze the data collected to examine how the completion of assignments included in the toolkit impacted the overall learning experience of trainees. This involved assessing the trainees' ability to critically reflect on their assumptions and biases, expectations, previous and current experiences, perceived challenges, and personal growth throughout the program, as well as their visions for future education and professional careers. The findings from this study inform our understanding of how reflective practice toolkits can contribute to positive outcomes and resilience among individuals engaged in a cancer research training program. In this presentation, we plan to discuss the importance of reflective practice in cancer disparity research education and the specific mechanisms through which it improved the trainees’ learning experiences and outcomes. We will also share the successes and challenges in implementing the toolkit and explore the potential for our toolkit to be utilized by similar training programs. Citation Format: Emily R. Kaminsky, Yuku Chen, Lin Zhu, Carolyn Fang, SJ Dodd. Developing and implementing an effective reflective practice toolkit on a cancer research training program [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B108.

Mentoring Minority Cancer Researchers of Tomorrow: Comparison of the Face-to-Face, Virtual, and Hybrid Training Methods of the CaRE2 Summer Cancer Research Education and Training Program.

In our previous publication, we reported a framework to develop an undergraduate cancer research training program at Florida A&M University (FAMU) under the umbrella of the Florida-California Cancer Research, Education, and Engagement (CaRE2) Health Equity Center activity by harnessing the resources available at FAMU, the University of Florida (UF), and the University of Southern California (USC) Cancer Centers. The implementation of the CaRE2 face-to-face training platform was dramatically affected by the COVID-19 pandemic during the summer of 2020 and 2021 training periods. However, a concerted effort was made to restructure the face-to-face training model into virtual and hybrid training methods to maintain the continuity of the program during the pandemic. This article compared the three methods to identify the best platform for training URM students in cancer disparity research. The program's effectiveness was measured through motivation, experiences, and knowledge gained by trainees during and one year after the completion of the program. The results showed that the participants were highly positive in their feedback about the professional and academic values of the program. Although the virtual and hybrid methods experienced significant challenges during the pandemic, the hybrid training module offered an "above average" effectiveness in performance, like the face-to-face mentoring platform in mentoring URM students in cancer disparity research.

0849 A Cross-Sectional Survey of Cannabis as a Sleep Aid in Canadian Cancer Survivors

Abstract Introduction Cannabis is increasingly used to manage cancer treatment-related symptoms. This study investigated the use and perceived effects of cannabis as a sleep aid in Canadian cancer survivors. Methods Canadian cancer survivors (N=1492) completed a self-report questionnaire about their use of cannabis as a sleep aid. Results Of participants, 24% (n=356) reported currently using cannabis as a sleep aid (Mage = 61; 88% white, 78% in remission). Two thirds (67%; n=238) report only starting to use cannabis for sleep after their cancer diagnosis. Reported benefits include that cannabis helps them relax (59%) and fall asleep faster (48%). Half of participants (49%) use cannabis for sleep over 4-6 times a week, meeting the criteria for regular cannabis use and 53% have been using cannabis as a sleep aid for more than 2 years. Cannabis is most commonly used in the form of edibles (58%) and oils/ sprays (45%). Only 19% have authorization from a healthcare provider and 56% obtain their cannabis from a government regulated site. There was a mix of cannabinoid content in the products used, including products that contain mostly CBD (22%), mostly THC (35%), balanced amounts of CBD and THC (32%), and 8% do not know the formulation of the cannabis they consume. The most common reasons for trying cannabis for sleep were a recommendation from family/friends (43%), their own research (35%), and that they believed it to be more natural than medication (31%). Of those who use cannabis for sleep, 31% also use it to reduce pain and 23% use it recreationally. Conclusion Estimates suggest that one in four Canadian cancer survivors’ regularly use cannabis to improve their sleep. Given the prevalence and potential impact, more research is needed to examine the actual efficacy of cannabis as a sleep aid. Support (if any) Rachel Lee is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds generously provided by the Canadian Cancer Society’s JD Irving, Limited – Excellence in Cancer Research Fund. Dr Garland is supported by a Canadian Cancer Society Emerging Scholar Award (Survivorship) (grant #707146).

0884 User Needs and Preferences for a Smartphone App to Treat Insomnia in Cancer Survivors

Abstract Introduction Cancer patients with insomnia have unique needs and require tailored healthcare interventions. iCANSleep is a mobile health intervention aimed at providing evidence-based insomnia treatment via a smartphone app. As part of a user-centered development process, virtual needs assessment interviews were conducted with cancer survivors who report insomnia to determine the needs and preferences of this patient group for insomnia treatment. Methods 22 cancer survivors from 5 Canadian provinces completed an online survey and participated in a needs assessment interview. Surveys were analyzed using descriptive statistics, while interviews were transcribed and analyzed using thematic analysis. Results 81.8% (18/22) of cancer survivors report that their insomnia started or was exacerbated during the time of their cancer diagnosis and treatment. Of the participants who discussed insomnia with a medical provider, hypnotic medications were prescribed in 64.3% (9/14) of cases. With some exceptions, participants reported strong familiarity with smartphone technology, had experience using apps for health management, and found an insomnia treatment app highly acceptable. Participant-identified facilitators of app use included ease of access, lack of cost, anonymity, empirical basis, and recommendation by local care teams. Smartphone ownership, cumbersome user interface, and limited access to internet were raised as potential challenges of implementation. Additional functionality identified by participants included options to link consumer wearable devices, additional modules to address comorbid conditions such as pain and anxiety, and an anonymous peer support forum. Conclusion Mobile apps hold promise as an avenue for the effective delivery of insomnia treatment; however, treatments must be evidence-based, and apps must be designed for maximum ease of use. Findings provide novel insight into how to best promote uptake and sustained use of mobile health interventions in cancer survivors and will be used to develop functional guidelines. Support (if any) Samlau Kutana is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the Canadian Cancer Society’s JD Irving, Limited – Excellence in Cancer Research Fund. Dr. Sheila Garland is supported by a Canadian Cancer Society Emerging Scholar Award (Survivorship) (grant #707146).

0868 Low-Fidelity Usability Testing of a Smartphone App to Treat Insomnia in Cancer Survivors

Abstract Introduction Cancer patients and survivors experience insomnia at a higher rate than the general population. Mobile health (mHealth) applications have considerable promise for the treatment of insomnia, but have been criticized for not following evidence-based treatment guidelines. To make insomnia treatment more accessible for survivors, iCANSleep has been developed using user-centered design principles to administer Cognitive-Behavioral Therapy for Insomnia via a smartphone app. The current research presents insights from the low-fidelity usability testing phase of development Methods Usability testing is an iterative process of testing an intervention’s user-interface and then applying the results to redesign the prototype to meet users’ needs. Eight cancer survivors from across Canada viewed a video demonstration of the app and completed semi-structured interviews about the app’s design and content. All interviews took place through video conferencing software and were recorded. Researchers transcribed interview responses and analyzed them for common themes. Results Participants (71% Female; Mage: 53) were generally very impressed with the design and layout of the app. Most (75%) participants were very interested in trying the app and reported that they would complete the app’s treatment program. Participants appreciated the integration of cancer-specific stories and material, the app’s simple, user-friendly design, the use of incentives and reinforcements, and the depth and breadth of its content. Those interviewed commented on the comprehensive sleep diary within the app and its apparent simplicity. Suggestions were made to streamline the onboarding and replace animations with real people. Conclusion User-centered development of the app is promising. The app’s patient-centeredness, accessibility, simplicity, and thoroughness were highlighted as strengths. The development team will integrate these results into the continued app development while working to make onboarding material more engaging. It is important to continue to engage patients throughout to ensure user engagement and effective care. Support (if any) Samlau Kutana is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by the Canadian Cancer Society’s JD Irving, Limited – Excellence in Cancer Research Fund. Dr. Sheila Garland is supported by a Canadian Cancer Society Emerging Scholar Award (Survivorship) (grant #707146).

Longitudinal Education and Career Outcomes of a Cancer Research Training Program for Underrepresented Students: The Meharry-Vanderbilt-Tennessee State University Cancer Partnership.

This study examined longitudinal education and career outcomes of the Meharry-Vanderbilt-Tennessee State University Cancer Partnership, the longest-running National Cancer Institute (NCI) Comprehensive Partnerships in Advancing Cancer Health Equity (CPACHE) program site in the United States. Degree completion rates were calculated and progression along the entire postsecondary "pipeline" was quantified for 204 participants recruited between 2011 and 2020. For participants who had entered the workforce, career outcomes were also analyzed. Relative to comparison data, participants completed degrees and progressed through the higher education "pipeline" to earn advanced degrees at remarkably high rates; the majority entered careers in which they support or conduct cancer research. The latter is important, because most participants identify with demographic categories currently underrepresented in the cancer research workforce. This article makes two contributions to knowledge on research training programs for underrepresented students: 1) it quantifies participants' progression along the entire postsecondary education pipeline as well as into the workforce, and 2) it identifies points where participants are most prone to exit the pipeline rather than progress. We identify two types of exits-permanent and temporary-and offer empirically supported operational definitions for both. Evaluators may find the quantitative model and/or definitions useful for analyzing similar programs.

Interprofessional Near-Peer Mentoring Teams Enhance Cancer Research Training: Sustainable Approaches for Biomedical Workforce Development of Historically Underrepresented Students.

A cancer research training program explored different approaches for staffing their in-person and virtual programs for high school students. The inclusion of undergraduate near-peer mentors had a universal benefit when implemented across in-person and virtual training programs of one- and ten-week durations. Benefits are described for four stakeholder groups: the high school trainees, program staff, scientist partners, and peer mentors themselves. Peer mentors described that their involvement enhanced their own professional development and, for some, drove a new interest in cancer research. Scientist partners described that peer mentors helped translate their work in the virtual environment for high school students. High school trainees reported their sessions with peer mentors to be one of their favorite parts of the program. Interprofessional peer mentors were highly relatable to students and modeled communication and paths in biomedical research. Staff reported that peer mentors supported student engagement during community shadowing sessions, allowing staff to focus on developing the shadowing experiences with partners. The benefit of including peer mentors was substantial from all viewpoints explored. Their intensive inclusion in cancer research training programs supports sustainability and capacity building in biomedical workforce development.

Knight Scholars Program: A Tiered Three-Year Mentored Training Program for Urban and Rural High School High School Students Increases Interest and Self-Efficacy in Interprofessional Cancer Research.

Cancer research training programs build our future biomedical workforce. Training is often centered for students residing close to research institutions, making access more challenging for rural students. A cancer research training program was developed for high school students residing in five geographical regions across Oregon. Training was tiered in duration and intensity across the three years, including a one-week Introduction program and subsequent 10-week summer research training programs (Immersion and Intensive). A total of 60 students participated in in-person and/or virtual training, with Immersion students receiving mentored shadowing experiences in clinical care, public health, and outreach in their home communities. Laboratory rotations at a research-intensive institution enabled students to sample research environments before selecting an area of interest for Intensive training the following summer. Aligning with Self-Determination Theory, the Knight Scholars Program aims to build competence, relatedness, and autonomy of its trainees in biomedical sciences. The program exposed students to a wide range of interprofessional careers and collaborative teams, enabling scholars to envision themselves in various paths. Results show strong gains in interest and research self-efficacy for both Introduction and Immersion scholars, with findings highlighting the importance of representation within mentoring and training efforts.

Improving Multi-site Interaction Through Remote Learning Technology: Report from a Training Program to Increase Underrepresented Undergraduate and Medical Students in Health Disparities Research.

Since 2018, we have evaluated the effectiveness of various teaching technologies for training young investigators on translational research in cancer health disparities. The Southeast Partnership for Improving Research and Training in Cancer Health Disparities (SPIRIT-CHD) unites Moffitt Cancer Center and the Louisiana State University Health Sciences Center. One of the main components of the SPIRIT-CHD is the Cancer Research Education Program (CREP) for training undergraduate and medical students from underrepresented backgrounds. The CREP utilizes a web-based didactic curriculum to engage students at both institutions in biobanking, precision medicine, and cancer health disparities topics. We report experiences from our cross-institutional cancer education program, specifically evaluating the cohorts' satisfaction and learning gains using various communication technologies and instructional approaches. Trainees completed a survey with questions evaluating the curriculum and technology. Trainees reported satisfaction with the flipped classroom model (FCM) content and overall program (mean score = 3.2, SD = 0.79), and would recommend the program to peers. Yet, despite improved program delivery, trainees felt interaction between the two sites (mean score = 1.5, SD = 0.85) and engagement with faculty (mean score = 2.80, SD = 1.14) could be improved. The technology with the highest reported use was e-mail, with a mean score of 4.6 (SD = 0.52). LinkedIn and Twitter had the lowest frequency of use with mean scores at 1.90 (SD = 0.99) and 1.30 (SD = 1.34). Our study highlights the successes and challenges of remote learning using technology to increase interaction and engagement among trainees and faculty in a multi-site cancer research training program.

A mixed methods needs assessment and gap analysis for establishment of a cancer research training program in East Africa.

BackgroundThe burden of non-communicable diseases (NCDs), including cancer, in Africa is rising. Policymakers are charged with formulating evidence-based cancer control plans; however, there is a paucity of data on cancers generated from within Africa. As part of efforts to enhance cancer research training in East Africa, we performed a needs assessment and gap analysis of cancer-related research training resources in Tanzania.MethodsA mixed-methods study to evaluate existing individual, institutional, and national resources supporting cancer research training in Tanzania was conducted. Qualitative data were collected using in-depth interviews while quantitative data were collected using self-administered questionnaires and online surveys. The study also included a desk-review of policy and guidelines related to NCD research and training. Study participants were selected to represent five groups: (i) policymakers; (ii) established researchers; (iii) research support personnel; (iv) faculty members in degree training programs; and (v) post-graduate trainees.ResultsOur results identified challenges in four thematic areas. First, there is a need for coordination and monitoring of the cancer research agenda at the national level. Second, both faculty and trainees identified the need for incorporation of rigorous training to improve research competencies. Third, sustained mentoring and institutional investment in development of mentorship resources is critical to empowering early career investigators. Finally, academic institutions can enhance research outputs by providing adequate research infrastructure, prioritizing protected time for research, and recognizing research accomplishments by trainees and faculty.ConclusionsAs we look towards establishment of cancer research training programs in East Africa, investment in the development of rigorous research training, mentorship resources, and research infrastructure will be critical to empowering local health professionals to engage in cancer research activities.

1031 Exploring the Impact of Cognitive Behavioral Therapy for Insomnia (CBT-I) on Daytime Productivity in Survivors of Breast Cancer

Abstract Introduction Post-treatment insomnia disorder and fatigue symptoms can impair work and daytime productivity in breast cancer survivors. Cognitive Behavioral Therapy for Insomnia (CBT-I) significantly improves insomnia and daytime fatigue. This feasibility study examined whether improving insomnia and fatigue using CBT-I is associated with improved work and activity productivity in breast cancer survivors. Methods 10 survivors of early stage breast cancer participated in 7 weekly individual CBT-I sessions. The primary outcome was the Work Productivity and Activity Impairment Questionnaire-General Health (WPAIQ-GH) questionnaire. Secondary outcomes were the Insomnia Severity Index (ISI) and the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF). Assessments were conducted at baseline and post-treatment. Paired samples t-tests examined the impact of CBT-I on productivity and fatigue. Linear regression assessed whether change in fatigue was associated with change in productivity. Results Participants had a mean age of 50.8 (range 42-63) and the majority were diagnosed with stage II (60%) cancer. There was a significant reduction in fatigue [t(9)= 2.43, p =.04] and activity impairment due to insomnia [t(9)= 3.105, p <.05] following treatment. Insomnia affected 52% of work productivity at baseline with a non-significant decrease to 15% following treatment [t(3)= 2.25 p= .110]. Reductions in fatigue were significantly associated with reductions in activity impairment [F(1,8)= 7.25, p =.03], accounting for 47.5% of the variability. Conclusion Treating insomnia with CBT-I significantly improved daytime productivity, activity impairment, and fatigue. Controlled research with larger sample sizes is warranted to confirm these preliminary results. Support Nyissa Walsh is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute (BHCRI). Dr. Sheila Garland is supported by a Scotiabank New Investigator Award from BHCRI.

1030 An Exploration of the Impact of Cognitive Behavioural Therapy of Insomnia (CBT-I) on Perceived Cognitive Impairment in Breast Cancer Survivors

Abstract Introduction Insomnia and cognitive impairment are prevalent and persistent symptoms in cancer survivors. Cognitive Behavior Therapy is effective for improving insomnia and comorbid symptoms in cancer survivors but there are very few empirically supported treatments that can improve cognitive impairment. This feasibility study explored the impact of CBT-I on perceived cognitive impairment in breast cancer survivors. Methods We enrolled 10 early stage breast cancer survivors with insomnia disorder and perceived cognitive impairment. Participants received 7 individual sessions of CBT-I over the course of 8 weeks and completed the Insomnia Severity Index (ISI), the Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) questionnaires and The Hospital Anxiety and Depression Scale (HADS) at baseline and post-treatment. Paired samples t-tests were used to assess change over time. Results The sample was predominantly diagnosed with stage II breast cancer (60%). Women were an average age of 50.8 (SD 6.84) and 18.2 (SD 3.62) years of education. CBT-I significantly reduced insomnia severity [19.4 to 7.1; t(9)= 6.56, p < .001] and improved perceived cognitive impairment [t(9)= -3.55, p < .01], perceived cognitive ability [t(9)= -2.87, p < .05], quality of life [t(9)= -3.14, p < .05], and overall subjective cognitive function [t(9)= -3.67, p < .01]. Although participants began treatment with low levels of mood disturbance, CBT-I further decreased symptoms of anxiety (baseline: M= 10.10, SD= 4.34; post-treatment M= 8.20, SD= 3.91) and depression (baseline: M= 7.90, SD= 3.45; post-treatment M= 5.30, SD= 2.83), although not statistically significant. Conclusion This study suggests CBT-I may improve perceived cognitive impairment in cancer survivors, in addition to insomnia and mood. Future randomized controlled trials with larger samples and objective measurements of cognition are needed. Support Nyissa Walsh is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute (BHCRI). Dr. Sheila Garland is supported by a Scotiabank New Investigator Award from BHCRI.

Developing a Novel Framework for an Undergraduate Cancer Research Education and Engagement Program for Underrepresented Minority Students: the Florida-California CaRE2 Research Education Core (REC) Training Program.

Lack of substantive research experiences and technical skills mentoring during undergraduate studies leaves many underrepresented minority (URM) students unprepared to apply to competitive graduate programs. As a part of our ongoing effort to increase the pipeline for the development and training of successful URM scientists in biomedical sciences with focus on reducing cancer health disparities, the Florida-California Cancer Research Education and Engagement (CaRE2) Health Equity Center was launched in 2018. Funded through an NIH/NCI U54 grant mechanism, the CaRE2 Center is a triad partnership among Florida Agricultural and Mechanical University (FAMU), a minority-serving institution, University of Florida (UF), and University of Southern California (USC) Cancer Center. One of the objectives of the triad partnership is to promote the coordination and implementation of the training of the next generation of Black and Latinx biomedical scientists in Florida and California. An important component of the CaRE2 program is the Research and Education Core (REC) designed to coordinate the training of URM students and researchers at different levels in their academic and professional developments. The undergraduate cancer research training program under FAMU-CaRE2 Center is a 3-year (2018-2021) project to identify, train, mentor, and provide the URM undergraduate students with the support network they need to flourish in the program and beyond. In its year-1 funding cycle, the program has made significant progress in developing a novel framework for an undergraduate cancer research education and engagement program at FAMU, one of the forefront minority institutions in the nation. The mentored research program is complemented with professional development and engagement activities, including cancer research seminars, workshops, and community outreach activities. The purpose of this paper is to discuss the strategies implemented for an effective partnership, the leadership and mentoring skills, and outcomes from the year-1 experiences. In addition, we present the progress made in advancing the pool of underrepresented minority students with scientific and academic career progression paths focused on cancer health disparities.

EVALUATION OF A TRANSDISCIPLINARY CANCER RESEARCH TRAINING PROGRAM FOR UNDER-REPRESENTED MINORITY STUDENTS.

Aim/PurposeThis paper will describe the initial development of systems to evaluate research education activities of a U.S. academic Partnership to train minority students as cancer researchers and provide preliminary data from monitoring Partnership activities during the first six months.BackgroundThere is increased focus on multidisciplinary/transdisciplinary research training programs. However, few training programs have included detailed evaluations to assess their outcomes and effectiveness.MethodologyThe Temple University/Fox Chase Cancer Center and Hunter College Regional Comprehensive Cancer Health Disparity Partnership (TUFCCC/HC Cancer Partnership, or the Partnership) is a recently-initiated center focused on training individuals from under-represented minorities (URMs) as cancer researchers. Evaluation of the training activities involves detailed specification of goals for each of the Partnership’s Cores; objectives for addressing each goal; measures and indicators to determine progress towards each objective; and data sources to provide information for the measures/indicators.ContributuionThis paper will provide important information for evaluation of training programs focused on students from URM populations and development of trans-disciplinary research education programs.FindingsGoals, objectives, measures, and data sources for evaluation of the Partnership’s Research Education Core (REC) were developed jointly by personnel from the REC and the Planning Evaluation Core (PEC) in an iterative process. These measures capture the training activities led by the REC (e.g., number of seminars and workshops), scientific output by trainees (e.g., papers and grants), and ability of the program to meet trainees’ goals and expectations.Recommendations for Practitioners and ResearchesEvaluation plans for transdisciplinary training programs need to be developed prior to program initiation. Evaluation measures should be jointly specified by training and evaluation personnel, then reviewed and revised in an iterative process.Impact on SocietyThis program is intended to enhance diversity among cancer researchers and increase studies to address disparities in cancer care.Future ResearchThe PEC will oversee the evaluation of Partnership training activities over the five year period and assist Partnership leaders in ensuring successful outcomes.

Twenty-five-Year Follow-up of Short-term Cancer Research Trainees at the University of Alabama at Birmingham: a Brief Report.

Long-term follow-up is needed to evaluate the impact of short-term cancer research programs on the career trajectories of medical and graduate students. Participation in these programs may be crucial in fostering the next generation of cancer research scientists. This report presents the career outcomes and research productivity of 77 medical and public health students with 25years of tracking data following their participation in a summer cancer research training program at the University of Alabama at Birmingham (UAB) in 1990-1998. Of 64 summer trainees with contact information, complete survey responses were received from 55 (86.0%) individuals. Over half reported clinical care of cancer patients and 18.2% stated that they were engaged in cancer research. Literature searches confirmed that 23.4% (18/77) of trainees have published cancer research papers. Future studies should explore the optimal timing of short-term post-baccalaureate academic cancer training experiences to identify participant characteristics and institutional factors that influence career choices and determine research productivity.

Gene Expression of Solute Carrier Organic Anion Transporters in Multidrug Resistant Breast Cancer Cells

IntroductionBreast cancer is the second leading cause of death due to cancer in women, and often becomes multidrug resistant (MDR) to adjuvant drug therapies due to the overexpression of ATP‐binding cassette (ABC) drug efflux transporters or through the decreased expression of drug uptake transporters, which can lead to treatment failure. MDR breast cancer cells can have complex drug translocation processes due to attempts to reduce intracellular anti‐cancer drug concentrations. It is critical to investigate possible drug targets for MDR cancers that can lead to increased drug accumulation. Solute carrier organic anion (SLCO) transporters are a family of transmembrane proteins that can uptake amphiphilic organic compounds into cells. Preliminary evidence suggests that SLCO transporters may be responsible for the targeted uptake of an emerging class of anticancer molecules called jadomycins, topoisomerase II and aurora B kinase‐targeting compounds which retain their cytotoxic potency in ABC‐transporter overexpressing MDR breast cancer cells.ObjectiveThe objective of this study is to evaluate the gene expression of SLCO transporters in a panel of breast cancer cell subtypes.MethodsThe mRNA expression 11 SLCO transporters was quantified using quantitative polymerase chain reaction (qPCR) in drug sensitive MCF7 (MCF7‐CON) and taxol (MCF7‐TXL), etoposide (MCF7‐ETP), and mitoxantrone (MCF7‐MITX) resistant MCF7 breast cancer cell lines which overexpress ABCB1, ABCC1, and ABCG2 drug efflux transporters, respectively. Comparisons were also made between BT474, SKBR3, and MDA‐MB‐231 breast cancer cell lines with different hormone receptor profiles as well as non‐cancerous MCF‐10A breast epithelial cells.ResultsGenerally, SLCO4A1 and 3A1 are significantly higher than the remaining transporters in drug resistant MCF7 cells, whereas this is not seen in the drug sensitive MCF7‐CON cells. There was significantly higher expression of: SLCO3A1 and 4A1 compared to the remaining transporters in MCF7‐MITX cells; SLCO3A1, 4A1, 4C1 compared to the remaining transporters in MCF7‐TXL cells; SLCO4A1 compared to the remaining transporters in MCF7‐ETP and SKBR3 cells; and SLCO3A1 and 4C1 versus all other transporters in MCF7‐ETP cells. There was significantly higher expression of SLCO1C1 versus SLCO3A1, 5A1, 1B3, 2B1, 1B1, 2A1, and 6A1 in MCF7‐CON cells.When differentiating between cancerous cells and non‐transformed MCF‐10A cells there were no significant differences between SLCO3A1 and any transporters found in breast epithelial MCF‐10A cells, however there was significantly higher expression of SLCO4A1 versus SLCO5A1, 1B3, 2B1, 1B1, and 4C1. Furthermore, there were no significant differences when comparing the transporters in BT474 and MDA‐MB‐231 cell lines.ConclusionSLCOs are differently expressed in breast cancer cell lines. SLCO4A1 and 3A1 were the most commonly expressed at significantly higher levels versus the other transporter genes in the cell lines used. They also were most highly expressed in the MDR MCF7 breast cancer cell lines and could serve as a conserved transport mechanism for intracellular delivery of anti‐cancer drugs, thereby suggesting they may be responsible for the cellular uptake of jadomycins. To explore this hypothesis, our future work will evaluate the jadomycin accumulation and cytotoxicity in SLCO3A1 and 4A1 knockdown cell lines.Support or Funding InformationLeah Bennett is a trainee in the Cancer Research Training Program of the Beatrice Hunter Cancer Research Institute, with funds provided by a CIBC Graduate Scholarship in Medical Research and the QEll Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract 326: Baseline IL-17 receptor signaling is essential for controlling aberrant JNK-dependent cellular proliferation via maintenance of endogenous level of ubiquitin-editing enzyme A20

Abstract The molecular mechanisms underlying aberrant activation of NF-κB and JNK in cancer remain incompletely understood. Here, we demonstrate that baseline IL-17 receptor (IL-17R) signaling is essential for controlling aberrant NF-κB and JNK activation, and restraining JNK-dependent homeostatic cellular proliferation. Using a shRNA knockdown approach, we demonstrated in B16 melanoma and 4T1 breast carcinoma murine cell lines that IL-17RA silencing markedly enhanced tumor cell growth in vitro and in vivo. Through mapping IL-17R signaling pathways, we further demonstrated that baseline IL-17A/IL-17R signaling actively restrained JNK phosphorylation in vitro and in vivo via the maintenance of basal expression of the ubiquitin-editing enzyme A20, a negative regulator of NF-κB and JNK. Remarkably, IL-17RA reconstitution evidently restored the A20 level, and suppressed cell proliferation and JNK activity in tumor cells. The reconstitution of A20 in IL-17RA knockdown subclones was able to restore the normal rate of cellular proliferation and associated JNK/c-Jun activity. Finally, meta-analysis of human cancer microarray and RNA-Seq datasets confirmed significant co-expression of IL-17RA and A20. Furthermore, alterations (mutation, upregulation or downregulation) of IL-17RA level in melanoma, ER+ breast cancer and colorectal cancer patients were associated with poorer overall survival compared to the respective patients with normal baseline IL-17RA expression. Together, our data demonstrates a previously unrecognized molecular mechanism underlying aberrant activation of NF-κB and JNK in cancer cells. This work highlights the unique biological role of proinflammatory IL-17R signaling in the maintenance of A20 to regulate the pathogenesis of human cancer, which draws caution on the utility of IL-17A neutralizing antibody in cancer therapy. CY is a PhD student supported by the graduate student scholarship from the IWK Health Centre and received a trainee award from the Beatrice Hunter Cancer Research Institute with funds provided by the Cancer Research Training Program as part of The Terry Fox Foundation Strategic Health Research Training Program in Cancer Research in CIHR. Citation Format: Chi Yan, Yang Lei, Anna L. Greenshields, David W. Hoskin, Tong-Jun Lin, Jun Wang. Baseline IL-17 receptor signaling is essential for controlling aberrant JNK-dependent cellular proliferation via maintenance of endogenous level of ubiquitin-editing enzyme A20 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 326. doi:10.1158/1538-7445.AM2017-326

Study of the Mechanisms of Jadomycin Cytotoxicity in Multidrug Resistant Triple Negative Breast Cancer Cells

BackgroundWe previously demonstrated that jadomycins, natural products biosynthesized by the soil bacteria Streptomyces venezuelae, are cytotoxic to drug‐sensitive and multidrug‐resistant breast cancer cells in vitro. Jadomycin cytotoxicity involves the generation of reactive oxygen species (ROS) but the downstream mechanisms contributing to cell death are not completely understood.ObjectiveTo determine if jadomycin anticancer mechanisms involve ROS‐mediated DNA damage and apoptosis in triple negative breast cancer cells in vitro.MethodsMDA‐MB‐231 control (231‐CON) and paclitaxel‐resistant (231‐TXL) breast cancer cells were treated with various concentrations of jadomycin B, F and S or the positive control drug mitoxantrone in the presence and absence of the ROS inducer auranofin or ROS inhibitor N‐acetylcysteine (NAC) for 24 to 36 hours. Western blotting for phosphorylated histone H2AX, a marker of DNA double strand breaks, was used to assess DNA damage. Annexin‐V‐FLUOS and propidium iodide flow cytometric analysis was used to measure apoptosis. The effect of jadomycin treatments on gene expression of topoisomerases IIα and IIβ (Topo IIα and IIβ, respectively) was measured using quantitative PCR. To study the direct inhibition of Topo IIα, Topo IIα decatenation of catenated circular kDNA was measured in the presence and absence of jadomycins.ResultsAll jadomycin treatments and mitoxantrone significantly increased histone H2AX phosphorylation (2.3 – 5.3‐fold) and early apoptosis (1.6 – 3.0‐fold) in 231‐CON and ‐TXL cells versus the vehicle control. NAC and auranofin did not alter jadomycin‐induced DNA damage or early apoptosis. However, auranofin did increase jadomycin‐induced necrosis/late apoptosis (2.7 – 4.5‐fold). Jadomycins caused a significant reduction of Topo IIα and IIβ mRNA expression (4.2 – 8.1‐fold decrease) and directly inhibited Topo IIα in the kDNA decatenation assays.ConclusionsJadomycins induce DNA double strand breaks and apoptosis in drug‐sensitive and multidrug‐resistant MDA‐MB‐231 breast cancer cells. These effects occur independently of ROS generation and may involve gene regulatory and functional inhibition of Topo IIα and IIβ.Support or Funding InformationThe study was funded by the Canadian Breast Cancer Foundation ‐ Atlantic Chapter, the Beatrice Hunter Cancer Research Institute, The Nova Scotia Health Research Foundation and the Dalhousie Pharmacy Endowment. S Hall was a recipient of an Izaak Walton Killam Predoctoral Scholarship. J MacLeod was a recipient of a Beatrice Hunter Cancer Research Institute Cancer Research Training Program Scholarship.

A Fulbright Specialist in Poland.

One of the greatest rewards in cancer education is working with colleagues from around the world. This manuscript reports on the development and conduct of a cancer research training program in Wroclaw, Poland, supported by the Fulbright Commission. The precipitating need for this program was the desire and lack of opportunity for medical trainees to develop skills necessary to conduct cancer education research. A 2-week program was developed consisting of didactic, Socratic, and individual/group consultations. Support from the Fulbright Commission was essential to the success of this program. Information will be presented in this paper on the completion of the funding application as well as lessons learned in the development and implementation of this program.

Automated Literature Searches for Longitudinal Tracking of Cancer Research Training Program Graduates.

A key outcome measure of cancer research training programs is the number of cancer-related peer-reviewed publications after training. Because program graduates do not routinely report their publications, staff must periodically conduct electronic literature searches on each graduate. The purpose of this study is to compare findings of an innovative computer-based automated search program versus repeated manual literature searches to identify post-training peer-reviewed publications. In late 2014, manual searches for publications by former R25 students identified 232 cancer-related articles published by 112 of 543 program graduates. In 2016, a research assistant was instructed in performing Scopus literature searches for comparison with individual PubMed searches on our 543 program graduates. Through 2014, Scopus found 304 cancer publications, 220 of that had been retrieved manually plus an additional 84 papers. However, Scopus missed 12 publications found manually. Together, both methods found 316 publications. The automated method found 96.2% of the 316 publications while individual searches found only 73.4%. An automated search method such as using the Scopus database is a key tool for conducting comprehensive literature searches, but it must be supplemented with periodic manual searches to find the initial publications of program graduates. A time-saving feature of Scopus is the periodic automatic alerts of new publications. Although a training period is needed and initial costs can be high, an automated search method is worthwhile due to its high sensitivity and efficiency in the long term.