Cancer therapy has aimed for years at selective killing of the cancer cells. Understanding the significance of the tumor microenvironment and the crosstalk between cancer and non-cancer cells in the tumor niche has provoked increasing efforts to treat the tumor as an organ. We hypothesized that tumor destruction can follow natural processes that lead to organ collapse in plants and animals. Using WST11, a Pd substituted bacteriochlorophyll and a modified photodynamic approach, successful tumor necrosis followed by boosting up of an anti-tumor immunity, has been shown in preclinical studies and already applied in Phase III clinical trials that have been recently accomplished in patients with localized prostate cancer. Superoxide, hydroxyl radical and peroxynitrite generation rather than singlet oxygen was shown to mediate tumor necrosis in an ischemia/reperfusion-like cascade of events. Non-covalent binding to serum albumin at intermediate binding affinity results in the drug confinement to the circulation and rapid clearance compared with other PDT reagents. Pre-clinical studies confirmed that WST11-VTP provokes systemic, anti-tumor immunity in multiple cancer indications when combined with application of immune checkpoint and Treg modulators. These results have provided the rational for new, four clinical trials at Memorial Sloan Kettering Cancer Center focusing on triple negative breast cancer, advanced prostate cancer, esophageal cancer and cancer of the urinary tract.