<p>I am not at all convinced of the staying power of protein drugs. Proteins are expensive to produce, often unstable, difficult to get into cells, also the immune system is constantly looking for foreign proteins to attack. Cells display protein fragments on their surface and immuno cells display fragments of proteins of pathogens recently destroyed. Any foreign proteins trigger an immune response.</p>
<p>You say that your main strengths are Math and Physics and you want to cure cancer. Maybe you should consider a degree in Medical Physics which is mainly concerned with using ionizing radiation to treat cancer. Research in this area could lead to new technologies and techniques for using radiation to cure cancers.</p>
<p>sschoe2: Protein drugs are the wave of the future and will be here for a long time to come. Every major therapeutic advance in cancer in the last decade has been attributed to some form of tyrosine kinase inhibit, monoclonal antibody, or even therapeutic vaccines! The science is really fascinating but you bring up good points regarding the challenges of protein based therapy. </p>
<p>Thankfully, science has addressed most of those issues! </p>
<p>As for medical physics, some very interesting things are happening - I recently worked on a compound that utilized a monoclonal antibody that served as a “carrier” for a radioactive isotope payload. It was fascinating work … essentially the protein mAb selectively targets cancer cells and releases this radioactive isotope in the vicinity effectively only killing the cancer cells. This increases efficacy and lowers side effects.</p>
<p>Pharma has brought all of this upon themselves. Pharma, and science in general, has become OBSESSED with things like understanding the mechanism of action of a molecular target and using all of the -omics du jours available that are (or were at least) supposed to help quicken the process of finding new miracle drugs. Well guess what, the way science is taught and pursued by many has led to failure after failure, and mediocre result after mediocre result. The obessions with picking molecular targets first and knowing all of the mechanisms of action has led to the massive failure of the pharma industry. Reductionist science is a joke. A cell is NOT simply an on/off switch, it has many other mechanism to bypass a pathway in case one shuts down. For example, just look at the way cells can create energy, if gluclose metabolism stops working, cells can change gear and still harvest energy through other pathways. The idea that we must pick a molecular target first and validate it before a new chemical entity can go into the clinic is the stupidest idea ever brought to pharma. If a chemical works, it works, who gives a rat’s ass how it works? In fact no where on the FDA’s list of approval guidelines does it even say that a mechanism of action MUST be shown for a new drug to get approved. Many, many classes of drugs were discovered and put into use before we even knew how they worked. Take the benzodiapines as an example. Maybe it is time we go back to the old way of how drug discovery used to be done–by doing pharmacology and screening based on phenotype responses first. </p>
<p>Pfizer though they knew ever single detail with regards to the cholesterol metabolic pathway, yet they lost $1billion on torcetrapib, a drug that failed in Phase III, that supposed had a mechanism of action within the cholesterol pathway. Genomics, proteomics, whatever -omics have also failed to produce any meaningful high impact results. It’s because genes, proteins, etc. DON’T act alone either, they all behave within the cell and all respond back and forth. Science should start taking more holistic approaches and move forward from there, even if all of the mundane details haven’t been worked out because quite simply, those details change all of the time based on a huge amount of variables that humans will always struggle to pinpoint.</p>
<p>On the flip side of your argument, no one understands alzheimer’s and one can see how well those drugs are doing in comparison to the results of molecular targeted compounds …</p>
<p>That’s because hardly anyone screens compunds based on phenotype response. People pick out what they think is a molecular target for AZ and screen from there. People spend years and millions of dollars doing this, and then they are surprised when molecules they find end up failing in tox studies it in the clinic? They should have realized that in all liklihood that many times molecules have more than 1 target, and simply running a screen on a cloned receptor and doing SAR from there fails because it takes a myopic view of the cell. Screening first on phenotype response makes so much more sense even if no one is ever able to work out the details.</p>
<p>I also doubt the viability of protein drugs. We have very very poor control over post translational modifaction of proteins. Some proteins are covered in a dense coating of sugars, and the sugar coatings themselves can be antigenic or change the role that some proteins have based on their glycosylation signatures.</p>