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Cobimetinib + atezolizumab + hydroxychloroquine is an investigational **combination therapy** evaluated primarily for **KRAS-mutated advanced malignancies** such as colon, rectal, lung, pancreatic, and stomach cancers[1][2][5][10]. The three agents function synergistically: - **Cobimetinib** is a **MEK inhibitor** (small molecule) that disrupts the MAPK/ERK pathway, thereby halting cancer cell proliferation[1][7]. - **Atezolizumab** is an **immune checkpoint inhibitor** (monoclonal antibody) targeting **Programmed death-ligand 1 (PD-L1)**, which enhances the immune system's ability to recognize and kill cancer cells[4][7]. - **Hydroxychloroquine** is an **autophagy inhibitor** (small molecule) that blocks lysosomal acidification needed for autophagy, thereby impairing cancer cell survival under stress. It is also a disease-modifying anti-rheumatic drug with immunomodulatory effects[1][3][6][9]. The combination is believed to increase tumor cell death and immune response against cancers with **KRAS mutations**, based on preclinical models and early-phase clinical trials[1][10].
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