Craig Crews, Lewis B. Cullman Professor of Molecular, Cellular and Developmental Biology and Professor of Chemistry; Executive Director, Yale Center for Molecular Discovery gave a talk at the 2018 Yale Assembly titled “Curing Cancer”. He started by discussing the balance that exists in our bodies of synthesizing and later degrading proteins. If one blocks the degradation of certain proteins, mutations in the genome would increase, which can lead to cancer formation. To combat this, physicians have been using drugs that block this protein buildup, like epoxomicin, however, these drugs often have serious side effects that can harm patients.
To better target chemotherapeutic drugs, Professor Crews has been exploring ways to deliver
drugs specifically to the tumor cells. To that end he has designed a carrier that is shaped like a dumbbell: it has two different ends, one that couples to a protein called an E3 Ligase (or ubiquitin ligase) and the other one attaches to a tumor cell. This way, E3 is linked to the tumor cell through the drug and can destroy it. Without the dumbbell drug, E3 would not have detected the tumor cell and hence would not have been able to destroy it. Furthermore, the drug has the capability of ‘moving on’ and tagging a new tumor cell, once it has successfully killed one cell. Since the drug is thus ‘reusable’, a much lower quantity of it needs to be present in the body, in comparison with conventional cancer drugs, which is a substantial benefit for the patient.
Clinical trials have started for this new drug which is intended to be prescribed to breast and prostate cancer patients. In addition, preliminary tests indicate potential efficacy of the drug for the treatment of Alzheimer’s disease.