PROJECT SUMMARY Further, more than one-quarter of cancer patients in Mexico suffer from a depression disorder and about half have significant mood disorder symptoms. Also, research shows is a prevalence of 67-82% clinical depressive symptoms in patients with advanced cancer. Patients with advanced cancer have specific needs; among the most pressing are to receive help in dealing with their mortality fears, uncertainty about the future, and spiritual concerns. However, there are no targeted psychosocial or psychotherapeutic interventions available for Latinos diagnosed with advanced cancer. Meaning-Centered psychotherapy (MCP) is a novel psychotherapeutic intervention designed to help patients with advanced cancer sustain or enhance a sense of meaning, peace and purpose as they approach the end-of-life. Meaning Centered Psychotherapy has been culturally adapted and found feasible in a pilot study with heterogenous Spanish-speaking Latinos with advanced cancer, but not yet tested with Mexican cancer patients. This study is a collaboration of investigators from two major cancer centers, Memorial Sloan Kettering Cancer Center (New York, where MCP f or Latinos, MCP-L, was adapted) and the National Mexican Cancer Institute (INCan, Spanish Acronym), the major public cancer center in Mexico and Central American region serving approximately 1000 new annual patients. Implementation of this project in INCan is feasible given the resources (psycho-oncology service with 3 full time psychologists) and institutional support for psycho-oncology research. Informed by implementation science framework, the objective of this study is to conduct a type 1 hybrid (testing effects of an intervention while gathering information on implementation) randomized clinical trial. The first aim examines the impact of Meaning Centered Psychotherapy for Mexicans on improving depression and anxiety (primary outcomes) and the secondary outcomes: distress, hopelessness, symptom burden and quality of life, compared to the control condition (cognitive behavioral therapy) at one and three months after treatment. We will also examine the mediation effect of spiritual and existential (meaning) well-being and moderation effect of socioeconomic hardship and literacy. Guided by a dissemination and implementation model and using a mixed-methods approach, the second aim examines the factors influencing the intervention implementation at the external, organizational, and patient levels, and potential implementation strategies. The third aim is to increase and support clinical and research capacity by providing specialized training to the INCan team and cancer MH providers from Latin American. This study is significant in that it targets the emotional impact of a diagnosis of advanced cancer in Mexican patients, a prevalent yet understudied need in this population. This study is innovative because it will be the first evidence-based psychotherapy intervention adapted for a low- and middle-income...