C/Can City Engagement Process: An Implementation Framework for Strengthening Cancer Care in Cities in Low- and Middle-Income Countries.

The effective implementation of locally adapted cancer care solutions in low- and middle-income countries continues to be a challenge in the face of fragmented and inadequately resourced health systems. Consequently, the translation of global cancer care targets to local action for patients has been severely constrained. City Cancer Challenge (C/Can) is leveraging the unique value of cities as enablers in a health systems response to cancer that prioritizes the needs of end users (patients, their caregivers and families, and health care providers). C/Can's City Engagement Process is an implementation framework whereby local stakeholders lead a staged city-wide process over a 2- to 3-year period to assess, plan, and execute locally adapted cancer care solutions. Herein, the development and implementation of the City Engagement Process Framework (CEPF) is presented, specifying the activities, outputs, processes, and indicators across the process life cycle. Lessons learned on the application of the framework in the first so-called Key Learning cities are shared, focusing on the early outputs from Cali, Colombia, the first city to join C/Can in 2017. Creating lasting change requires the creation of a high-trust environment to engage the right stakeholders as well as adapting to local context, leveraging local expertise, and fostering a sustainability mindset from the outset. In the short term, these early learnings inform the refinement of the approach in new cities. Over time, the implementation of this framework is expected to validate the proof-of-concept and contribute to a global evidence base for effective complex interventions to improve cancer care in low- and middle-income countries.

Strengthening Pathology Capacity to Deliver Quality Cancer Care in Cities in LMICs.

Diagnostic pathology services for oncology health systems are essential; yet, surveys, observations, and hard data from across low- and middle-income countries have revealed that these services are almost always lacking adequate quality and often missing completely. The City Cancer Challenge Foundation (C/Can), the American Society for Clinical Pathology, and C/Can partner cities undertook intense analysis of their existing pathology services as part of a year-long assessment process including the specific formation of a pathology-focused team. Internal and external expert assessments identified sustainable solutions adapted to the local context and level of resources and created specific local implementation projects. Through local leadership, capacity development, and collaboration, services were improved city-wide in three cities: Cali, Colombia; Asunción, Paraguay; and Yangon, Myanmar. Common problems identified across cities included deficiencies in personnel training, equipment, reagents, processes, quality, and coordination. Specific solutions included quality training, standard process development and regulation, implementation of new services, and public-private collaboration. As the first cities joining the C/Can initiative, Cali, Asunción, and Yangon demonstrate the success of the approach and the value of local expertise in identifying problems and solutions. The additional value of international partners' expertise created opportunities for growth through mentorship and technical support. Importantly, the power of healthcare programs with strong political support is emphasized.

Advancing Reliable Data for Cancer Control in the Central America Four Region.

The Central America Four (CA-4) region, comprising Guatemala, Honduras, El Salvador, and Nicaragua, is the largest low- and middle-income country region in the Western Hemisphere, with over 36 million inhabitants. The CA-4 nations share a common geography, history, language, and development indices, and unified with open borders in 2006. The growing CA-4 cancer burden among the noncommunicable diseases is expected to increase 73% by 2030, which argues for a regional approach to cancer control. This has driven efforts to establish population-based cancer registries as a central component of the cancer control plans. The involvement of international and academic partners in an array of initiatives to improve cancer information and control in the CA-4 has accelerated over the past several years. Existing data underscore that the infectious cancers (cervical, stomach, and liver) are a particular burden. All four countries have committed to establishing regional population-based cancer registries and have advanced significantly in pediatric cancer registration. The challenges common to each nation include the lack of national cancer control plans and departments, competing health priorities, lack of trained personnel, and sustainability strategies. General recommendations to address these challenges are outlined. The ongoing regional, international, and academic cooperation has proven helpful and is expected to continue to be a powerful instrument to contribute to the design and implementation of long-term national cancer control plans.

Perspectives on Strengthening Cancer Research and Control in Latin America Through Partnerships and Diplomacy: Experience of the National Cancer Institute's Center for Global Health.

According to the Pan American Health Organization, noncommunicable diseases, including cancer, are the leading causes of preventable and premature death in the Americas. Governments and health care systems in Latin America face numerous challenges as a result of increasing morbidity and mortality from cancer. Multiple international organizations have recognized the need for collaborative action on and technical support for cancer research and control in Latin America. The Center for Global Health at the US National Cancer Institute (NCI-CGH) is one entity among many that are working in the region and has sought to develop a strategy for working in Latin America that draws on and expands the collaborative potential of engaged, skilled, and diverse partners. NCI-CGH has worked toward developing and implementing initiatives in collaboration with global partners that share the common objectives of building a global cancer research community and translating research results into evidence-informed policy and practice. Both objectives are complementary and synergistic and are additionally supported by an overarching strategic framework that is focused on partnerships and science diplomacy. This work highlights the overall strategy for NCI-CGH engagement in Latin America through partnerships and diplomacy, and highlights selected collaborative efforts that are aimed at improving cancer outcomes in the region.

Association of Over-Expressed Estrogen Receptor Alpha with Development of Tamoxifen Resistant Hyperplasia and Adenocarcinomas in Genetically Engineered Mice.

BACKGROUND: Estrogen receptor alpha (ERα) and cyclin D1 are frequently co-expressed in human breast cancer. Some, but not all, studies link tamoxifen resistance to co-expression of cyclin D1 and ERα. In mice over-expression of either cyclin D1 or ERα in mammary epithelial cells is sufficient to induce mammary hyperplasia. Cyclin D1 over-expression in mice leads to mammary adenocarcinoma associated with activated estrogen signaling pathways. ERα over-expression in mice leads to mammary hyperplasia and cancer. Significantly, disease development in these mice is abrogated by loss of cyclin D1. METHODS: Genetically engineered mouse models were used to determine whether or not ERα over-expression demonstrated cooperativity with cyclin D1 over-expression in cancer development, reaction to the chemical carcinogen DMBA, or tamoxifen response. RESULTS: Adding ERα over-expression to cyclin D1 over-expression increased the prevalence of hyperplasia but not cancer. Single dose DMBA exposure did not increase cancer prevalence in any of the genotypes although cyclin D1 over-expressing mice demonstrated a significant increase in hyperplasia. Tamoxifen treatment was initiated at both young and older ages to test for genotype-specific differences in response. Although normal ductal structures regressed in all genotypes at both younger and older ages, tamoxifen did not significantly reduce the prevalence of either hyperplasia or cancer in any of the genotypes. All of the cancers that developed were hormone receptor positive, including those that developed on tamoxifen, and all showed expression of nuclear-localized cyclin D1. In summary, development of tamoxifen resistant hyperplasia and cancer was associated with expression of ERα and cyclin D1. CONCLUSION: These preclinical models will be useful to test strategies for overcoming tamoxifen resistance, perhaps by simultaneously targeting cell cycle regulatory pathways associated with cyclin D1.