Mechanisms of Action in Oncology

Targeted Therapies

The American Society of Clinical Oncology recommends trastuzumab + chemotherapy in HER2+ disease, which targets the HER2 pathway in gastric cancer 1
Antiangiogenic agents prevent the formation of new blood vessels by inhibiting VEGF, potentially disrupting neurogenesis and causing vascular dysfunction 2
Proteasome inhibitors prevent the breakdown of pro-apoptotic proteins, enabling programmed cell death in cancer cells, but may cause amyloid-β aggregation from disruption of proteostasis 2

Immune checkpoint inhibitors block checkpoint proteins (PD-1/PD-L1, CTLA-4) from binding with partner T cells, enabling cancer cell killing by the immune system 1
Combined immunotherapy with multiple checkpoint blockade (e.g., nivolumab + ipilimumab) shows synergistic effects in certain tumors like NSCLC 1

Anthracyclines block DNA damage repair and disrupt cell cycle, causing mitochondrial dysfunction and oxidative stress 2
Platinum agents crosslink DNA strands to inhibit DNA function and synthesis, causing apoptosis 2, 3
Taxanes promote microtubule assembly and block dissociation, preventing mitosis in cancer cells 2, 3
Antimetabolites interrupt synthesis of DNA and RNA in cancer cells, with agents like methotrexate impairing neurogenesis 2

Combinations of chemotherapy + immunotherapy show improved efficacy with modest increases in toxicity across multiple tumor types 1, 4
Combinations of targeted therapy + chemotherapy, like trastuzumab with chemotherapy in HER2+ gastric cancer, improve outcomes 1

Chemotherapy-specific toxicities include neutropenia, anemia, thrombocytopenia, and peripheral neuropathy 1, 3
Immunotherapy-specific toxicities include thyroid dysfunction, pneumonitis, and immune-related adverse events 1, 4
Combination-induced toxicities include increased risk of diarrhea, rash, and liver enzyme elevation when combining immunotherapy with chemotherapy 1

Phenotypic profiling uses cell-based assays to identify cellular response "fingerprints" that identify mechanisms of action for both efficacy and safety 6
Pathway-based approaches integrate diverse datasets from disease names and clinical symptoms through cell types and pathways to genes, mutations, and drugs 7