Arseniy E. Yuzhalin's article "Redefining Cancer Research for Therapeutic Breakthroughs" highlights the challenges and opportunities in cancer research. Despite significant investments, the translation of basic research into substantial advancements in cancer treatment has been limited. The article critiques the current approach, which relies heavily on methodological reductionism, a scientific method that breaks down complex systems into smaller, more manageable components. While this approach has been effective for diseases defined by a single parameter, it falls short in understanding multifactorial disorders like cancer. The holistic approach, which emphasizes studying complex systems as integrated wholes, has gained popularity in recent years. Single-cell sequencing studies, for example, provide insights into the clonal evolution and intratumoral heterogeneity of tumors, but these studies often generate large amounts of data that have not yet translated into effective therapies. The article also notes that the 5-year cancer survival rate has stagnated, and the incidence and mortality of cancer continue to rise, partly due to the aging population and the decline in the disruptiveness of science and technology. To address these challenges, the author suggests a balanced approach between reductionism and holism, prioritizing functional studies over mechanistic ones. High-risk, high-reward approaches are also recommended to foster disruptive science. The article concludes with a call for a paradigm shift in cancer research to enhance innovation and ultimately bring therapeutic breakthroughs, aiming to completely eradicate cancer-associated mortality and disability.Arseniy E. Yuzhalin's article "Redefining Cancer Research for Therapeutic Breakthroughs" highlights the challenges and opportunities in cancer research. Despite significant investments, the translation of basic research into substantial advancements in cancer treatment has been limited. The article critiques the current approach, which relies heavily on methodological reductionism, a scientific method that breaks down complex systems into smaller, more manageable components. While this approach has been effective for diseases defined by a single parameter, it falls short in understanding multifactorial disorders like cancer. The holistic approach, which emphasizes studying complex systems as integrated wholes, has gained popularity in recent years. Single-cell sequencing studies, for example, provide insights into the clonal evolution and intratumoral heterogeneity of tumors, but these studies often generate large amounts of data that have not yet translated into effective therapies. The article also notes that the 5-year cancer survival rate has stagnated, and the incidence and mortality of cancer continue to rise, partly due to the aging population and the decline in the disruptiveness of science and technology. To address these challenges, the author suggests a balanced approach between reductionism and holism, prioritizing functional studies over mechanistic ones. High-risk, high-reward approaches are also recommended to foster disruptive science. The article concludes with a call for a paradigm shift in cancer research to enhance innovation and ultimately bring therapeutic breakthroughs, aiming to completely eradicate cancer-associated mortality and disability.