Cancer cells exhibit several key structural and functional features that make them distinct from normal cells. These features can be targeted by drugs to selectively kill cancer cells while sparing healthy cells. Medicinal chemists can optimize the design of such drugs to increase their efficacy and minimize side effects. Some of the key features that can be targeted include:1. Rapid cell division: Cancer cells divide more rapidly than normal cells, leading to uncontrolled growth and the formation of tumors. Drugs that target the cell division machinery, such as microtubule inhibitors e.g., taxanes or DNA synthesis inhibitors e.g., antimetabolites , can selectively kill cancer cells.2. Abnormal cell signaling: Cancer cells often have mutations in signaling pathways that regulate cell growth and survival. Drugs that target these pathways, such as tyrosine kinase inhibitors e.g., imatinib or monoclonal antibodies e.g., trastuzumab , can selectively kill cancer cells by inhibiting their growth and survival signals.3. Angiogenesis: Tumor growth requires the formation of new blood vessels to supply nutrients and oxygen. Drugs that inhibit angiogenesis, such as vascular endothelial growth factor VEGF inhibitors e.g., bevacizumab , can selectively kill cancer cells by cutting off their nutrient supply.4. Immune evasion: Cancer cells can evade the immune system by expressing immune checkpoint proteins that inhibit immune cell activation. Drugs that target these immune checkpoints, such as programmed cell death protein 1 PD-1 inhibitors e.g., pembrolizumab or cytotoxic T-lymphocyte-associated protein 4 CTLA-4 inhibitors e.g., ipilimumab , can selectively kill cancer cells by unleashing the immune system against them.To optimize the design of drugs targeting these features, medicinal chemists can employ several strategies:1. Structure-based drug design: By understanding the molecular structure of the target protein or enzyme, chemists can design drugs that specifically bind to and inhibit their function. This can lead to increased selectivity and reduced off-target effects.2. Prodrug strategies: Prodrugs are inactive compounds that are converted into their active form within the body, often by enzymes that are overexpressed in cancer cells. This can increase the selectivity of the drug for cancer cells and reduce side effects in healthy tissues.3. Drug delivery systems: Nanoparticles, liposomes, or antibody-drug conjugates can be used to selectively deliver drugs to cancer cells, increasing their concentration at the tumor site and reducing exposure to healthy tissues.4. Optimization of pharmacokinetic properties: Medicinal chemists can modify the chemical structure of drugs to improve their absorption, distribution, metabolism, and excretion ADME properties. This can lead to increased drug efficacy and reduced side effects.5. Combination therapies: Combining drugs that target different aspects of cancer cell biology can increase the overall efficacy of treatment and reduce the likelihood of drug resistance.By employing these strategies, medicinal chemists can design drugs that selectively target cancer cells, increasing their efficacy and minimizing side effects for patients.