Our laboratory seeks to understand how tumor suppressor and oncogene status regulate autophagy, and thus modulates response to therapy. Through an academic-industry collaboration, we evaluated the ability of novel compounds to inhibit autophagy in cancer cells. Two publications in the Cell Press journal iScience highlight our findings, which serve as strong evidence for preclinical studies investigating the therapeutic potential of a selective compound, ULK-101. Our interest in autophagy inhibitors spans beyond targeting ULK1 to other nodes in the pathway, and as such, we have also leveraged predictive computational modeling, quantitative microscopy, and in silico screening to predict the therapeutic benefit of inhibiting autophagy in cancer. Our research suggests that additional kinase inhibitors modulate autophagy, and may be more selective and effective than current lysosomotropic agents. Our goal is to identify and develop compounds that lead to improved autophagy inhibition, thereby paving the way for new therapeutic options in oncology and other disease settings.