Julia Draznin Maltzman, MD
Abramson Cancer Center of the University of Pennsylvania
New this year at ASCO is a plenary science presentation. To mark the beginning of this tradition Dr. Leland H. Harwell was chosen for this honorable task. Dr. Harwell won a Nobel Prize in medicine in 2001 for his work in yeast genetics. He is credited with understanding how normal cells divide and the mechanisms leading to the uncontrolled growth that causes cancer. He has now focused his efforts in directing the Fred Hutchinson Cancer Center in Seattle WA and gave the plenary science address at this years ASCO about his perception of the future of Oncology.
Dr. Harwell argued that we have today the science and technology to improve cancer care. What we are lacking, however, is a method of organization and integration of all the available information so that it could be translated into improved patient care.
The past forty years, we have achieved understanding of molecular biology of cancer. We have even come to better understand some of the mechanisms involved in cell cycle, cell division, cell growth, apoptosis, metastasis, differentiation, and adhesion. We now also have a map of the entire human genome. New insight into cancer stem cells also helped scientists understand the biology of cancer. However, with all the new technology and resources, what we are missing, argues Dr. Harwell, is the ability to translate this into improved cancer outcomes. We still cannot stop the progression of cancer and we still do not come close to curing it in many people.
If we want to begin to achieve this lofty goal of cancer eradication, we have to focus on proteins says Dr. Harwell. This Nobel Laureate believes that we should not spend the money, time, and effort in developing new therapeutics or even looking for novel targets of these therapeutics. Rather, he believes that we should concentrate our efforts on improving molecular diagnostics, particularly proteomics. Our current drug armamentarium may, in fact, be sufficient, if we know how to better direct these agents. If only the patients who stand to benefit are exposed to the drug, then there are fewer toxicities seen and increased effectiveness noted.
Transcript arrays have already begun to stratify cancers and certain therapeutics are aimed only at the people in whom they will see an affect. However blindly searching for another specific targeted agent (like Gleevec, for example) may be frustrating. The frustration is largely due to the enormous cost of research and development, the poor predictive value of currently existing animal models, and the incredible length of time necessary to develop a drug. He further added that, potential therapy might require combination targeted therapies over a single agent targeted approach. Therefore, to avoid getting trapped in this frustration Dr. Harwell proposes developing improved diagnostic tools that could enable us to target our therapies. This may also result in a better narrowing the potential toxicities and shorten the length of clinical trials, as we will be dealing with a more appropriate patient population for the therapeutic in question. Dr. Harwell proposes developing more cheap and effective diagnostic and screening tests to identify a population in need and address their concerns early. The most powerful tool we have to enable early detection is via protein analysis. Proteins can be sought from easily accessible mediums such as blood, and are less invasive than DNA or RNA techniques.
Dr. Harwell notes that proteins are more dynamic, more informative and more predictive of the state of the cancer cell. They are more diverse because although a complete DNA complement exists in every cell, only some of the proteins are transcribed in an individual cell at any given time. To site another example, identical transcription messages may encode for two different protein isomers. The diverse and dynamic nature of proteins make them more difficult to work with but much more informative.
Dr. Harwell stressed not only that we need to improve techniques to find proteins characteristic of disease, we must also improve available techniques to validate these proteins. High throughput techniques must be developed to validate all the proteins identified and identify any novel protein signatures that may be hallmarks of cancer. Such techniques may include rigorous biomarker screens and high quality genetically engineered mouse model of cancer. He also noted the need for better bio-informatics platforms to support these integrated studies. In other words, improved technology would generate a tremendous amount of data thus computer software is needed to be able to assess the identified proteins and through multiple complex permutations identify potential causative agents. Furthermore, he emphasized the need for centralized organizations of funding for these seemingly disparate efforts.
Improved molecular diagnostics, he argued, provide a greater opportunity to find the disease early while it is still potentially in a curable stage.
Dr. Harwell felt strongly that such a coordinated effort cannot come from industry. Protein efforts are not lucrative and therefore not desirable business investments. However, Dr. Harwell notes, only if proteomics develops into a rigorous science, can we then begin to "cure cancer".
Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.English