https://www.selleckchem.com/products/mln-4924.html Patients with advanced cancer suffer from psychosocial distress that may impair quality of life and that may be ameliorated by psychotherapeutic treatment. We describe here the methodology of a randomized controlled trial (RCT) to assess the effectiveness of a novel, brief, semi-structured psychotherapeutic intervention to reduce distress and increase well-being in patients with advanced or metastatic cancer. The intervention, called Managing Cancer and Living Meaningfully (CALM), was originally developed in Canada and we are now testing its Italian adaptation (CALM-IT). The study is a single-blinded phase III RCT with assessment at baseline, 3 and 6 months with two conditions CALM-IT versus a nonspecific supportive intervention (SPI). Eligibility criteria include ≥ 18 years of age; fluency in the Italian language; no cognitive deficit, and diagnosis of advanced or metastatic cancer with an expected survival of 12-18 months. CALM-IT includes up to 12 sessions, delivered over 6 months and covers 4 domains i) Symptom Management and Communication with Health Care Providers; ii) Changes in Self and Relations with Close Others; iii) Sense of Meaning and Purpose; and iv) the Future and Mortality. The primary outcome is difference in severity of depressive symptoms between treatment arm and the primary endpoint is 6 months. The secondary endpoint is 3 months and secondary outcomes are generalized anxiety, distress about dying and death, demoralization, spiritual well-being, attachment security, posttraumatic growth, communication with partners, quality of life, and satisfaction with clinical care. If shown to be effective, CALM-IT can be implemented nationally to relieve distress and to promote psychological well-being in patients with advanced cancer.Huntingtin-associated protein 1 (HAP1) is a polyglutamine (polyQ) length-dependent interactor with causal agents in several neurodegenerative diseases and has been regarded a