Team:Penn/ProjectOverview

Medicine is a challenge of optimization. When treating a disease, doctors and physicians want to maximize the on-target, beneficial effects of a therapy while minimizing the off-target or side effects. We identified two main optimization parameters for current medical therapies: specificity and dosage control.

Current therapies generally rely on either spatial targeting (within a physical area) or cellular targeting (to a specific antigen or biomarker). However, these methods still have high nonspecific effects on healthy tissue. For example, cancer radiation therapy can spatially target and kills tumor cells, but it effects all cells in the target area. Effectiveness of radiation therapy is therefore limited to when the cancer is highly localized and when the tumor area is well defined. Chemotherapy and monoclonal antibody therapies are able to target by cell type, but they target even healthy cells throughout the body that express the antigen or biomarker. This is why patients undergoing chemotherapy exhibit horrible side effects: the treatment targets and kills all rapidly dividing cells, including healthy hair, skin, and organ cells.

Spatial Targeting: Surgeons excise a tumor manually, without regard for cellular heterogeneity within and around the tumor area.	Cellular Targeting: Monoclonal antibodies identify antigens on certain cells or viruses. Monoclonal antibodies are often coupled with therapeutic agents. However, if the antigen is present in healthy tissue outside the diseased area, it will be targeted as well.

Precise dosage control is difficult in current medical therapies. Relying on passive diffusion makes dose precision hard to determine – of the dose injected into the body, how much of it actually reaches its target? Innovation in pharmacology therefore focuses on increasing the therapeutic window - the range of drug dose that is considered both effective and safe – so that doses may be increased if necessary. Modern chemical therapise then focuses on maximizing the amount of time a drug dose falls in the therapeutic window, while being careful to not overlap into the range of toxicity. The riskiest drug therapies therefore becomes a race – will the treatment kill the disease before the treatment kills the patient?

Therapeutic Window: Modern drug therapy focuses on maintaining an effective concentration of a drug within the therapeutic window by timing of doses. It is very difficult to maintain a constant dose, however, which leads to the risk of overdosing.	Toxic and Lethal Effects: If drug doses become too high, toxic or even lethal effects may occur. In the riskiest drug therapies such as chemotherapy, there is very little space between the Effective Dose, Toxic Dose, and Lethal Dose curves, making dose control incredibly important.