Antibody-drug conjugates (ADCs)

What do you know about antibody-drug conjugates (ADCs)? I don't recall learning about them in medical school. You probably haven't either. However, I'm sure that most oncologists have heard of ADCs.

Genentech (now a member of the Roche Group), is researching ADCs because this therapeutic option may have the potential to treat cancer and improve patients’ lives. I'm now quoting from a commerical website (www.ResearchADCs.com):

An ADC is a unique combination of a precise and targeted monoclonal antibody, a stable linker, and a potent cytotoxic and is designed to more selectively kill cancer cells while minimizing effects on normal tissue.

Will research surrounding ADCs lead to a cure for cancer? I think that most experts will agree that the future of cancer therapy will significantly revolve around targeted biologic agents and small molecules. If you're thinking about a research career, it's probably a good time to be a molecular biologist who also has extensive knowledge about nanotechnology. 

Nanotechnology to Fight Cancer

This is a guest post by Teresa Jackson. 

Nanotechnology to Fight Cancer

It’s arguably the most horrible disease known to man, and even though it’s been around for ages, we’re yet to find a cure for this deadly illness we know as cancer. It’s a poison that kills you slowly, and with a great deal of physical and emotional pain and suffering. But that’s not the worst part – what’s really unbearable is that you know you’re definitely going to die, and suffer through the process. But if there’s one spark of hope for those who’re being affected by the disease, it’s the one being generated by the field of nanotechnology.

The problem with current methods of treatment of cancer is that they destroy healthy cells as well when they destroy the cancerous ones. And this causes you to suffer side effects and other adverse consequences. Nanotechnology comes to the rescue in such situations by targeting only the cancerous cells using tiny particles that are used to inject the cancer-killing medicine exactly where they’re needed and nowhere else. This form of targeted therapy is now being used not only to deliver medication but also to turn off the proteins that are associated with and contribute to the growth of cancerous cells.

Genomics and Personalized Medicine

The topics of genomics and personalized medicine are very hot topics these days. Let's start by seeing how Wikipedia defines these terms:

Genomics:

Genomics is the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis, epistasis, pleiotropy and other interactions between loci and alleles within the genome. In contrast, the investigation of the roles and functions of single genes is a primary focus of molecular biology or genetics and is a common topic of modern medical and biological research. Research of single genes does not fall into the definition of genomics unless the aim of this genetic, pathway, and functional information analysis is to elucidate its effect on, place in, and response to the entire genome's networks.

Personalized Medicine

The United States Congress defines personalized medicine as "the application of genomic and molecular data to better target the delivery of health care, facilitate the discovery and clinical testing of new products, and help determine a person's predisposition to a particular disease or condition."

The application of personalized medicine is being studied heavily in the area of oncology. Tailored therapies are being developed for patients who have specific genetic mutations. Targeted biologic agents are being used to treat diseases at the molecular level. The definition of the term "bioengineering" or "biological engineering" will continue to evolve as we see tremendous advances in medical technology.

Protein linked to lung cancer

We know that smoking and radon can cause lung cancer. As we learn more about the biology of malignant tumors, hopefully we will see some cancer cures emerging on the horizon. The latest research from the David H. Koch Institute for Integrative Cancer Research at MIT suggests that the protein NF-kappaB could be a novel target for cancer drugs. According to this recent MIT News story:

NF-kappaB is a transcription factor protein that is normally activated when a cell is under attack from a virus or bacterium. Previous studies have suggested that constant activation of NF-kappaB enhances survival of tumor cells.

The research findings were published in Nature and I'm eager to read the entire study. The key points were that the expression of the cancer gene ras and loss of the tumor suppressor gene p53 activates activate NF-kappaB. So, lung cancer patients who have this combination could be treated by a drug that targets NF-kappaB.

2009 ASCO EHR Symposium

The 2009 ASCO (American Society of Clinical Oncology) Electronic Health Record (EHR) symposium is this October in San Francisco, CA. Because of the HITECH provisions found in the ARRA, we know that EHRs will become very prevalent across all medical specialties, including oncology.

In the field of oncology, so many medications cause significant adverse reactions. Plus, combination therapy is often used to treat cancer. EHRs can help clinicians keep track of all the treatment infusions and they may also alert providers about the possible risks associated with combining certain chemotherapy agents with targeted biologics.

Interested in knowing who will be speaking? Here are just a few examples:

• Peter Yu, M.D. - Chair ASCO EHR Workgroup, Oncologist, Palo Alto Medical Foundation (PAMF)
• Barbara McAneny, M.D. - CEO, New Mexico Oncology Hematology Consultants
• Charles McKay, M.D. - CEO, Tennessee Oncology
• John Cox, D.O., M.B.A. - Editor-in-Chief, Journal of Oncology Practice
• Robert Miller, M.D. - Oncologist, Johns Hopkins Kimmel Cancer Center
• Kenneth Buetow, Ph.D. - Director, NCI's Center for Biomedical Informatics and Information Technology (CBIIT)
• Lawrence Shulman, M.D. - Chief Medical Officer, Dana- Farber Cancer Center
• William Hersh, M.D. - Chair, Department of Medical Information and Clinical Epidemiology, Oregon Health and Sciences University

If you're an oncologist (and you're not retiring anytime soon), you won't want to miss this! To get more information about the ASCO EHR symposium, visit: http://www.asco.org/ehrsymposium

Arzerra (ofatumumab) appears promising for CLL

Arzerra (ofatumumab) appears promising for chronic lymphocytic leukemia (CLL). Ofatumumab (formerly known as HuMax-CD20) is a targeted therapy. It is actually a human monoclonal antibody that targets a distinct antibody binding site (the small loop epitope) of the CD20 molecule on the cell membrane of B cells. It is currently under development for the treatment of CLL and has also shown potential in treating follicular non-Hodgkin’s lymphoma, diffuse large B cell lymphoma, rheumatoid arthritis and relapsing remitting multiple sclerosis. Is it available yet? No. The FDA is currently still reviewing this biologic agent. Here's a snippet from the June GSK press release:

GlaxoSmithKline and Genmab A/S today announced that the United States Food and Drug Administration (FDA) informed the companies that the agency has extended the action date for the ofatumumab BLA application by three months.

The FDA has been slow recently, don't you think? Better safe than sorry? Or, is the FDA being overly-cautious? We don't want to see another Raptiva incident again, do we? Raptiva was voluntarily withdrawn in April by Genentech because of an increased risk of progressive multifocal leukoencephalopathy (PML), a rare and usually fatal disease of the central nervous system. It's difficult to find such rare adverse effects until the drug gets used by the public, so I don't think anyone is faulting either the FDA or Genentech.

Well, let's see what happens with ofatumumab.

Personalized Cancer Treatment

Each person who develops cancer has a unique condition. The world of oncology isn't driven by a cookbook approach (although sometimes it may seem like it). What does it mean to receive personalized cancer treatment? Are we talking about personalized medicine? Genomics? The use of biologic targeted therapies that are designed to combat cancer on the molecular level? The application of nanotechnology to improve drug delivery?

Have you heard of Champions Biotechnology? They've created a new website dedicated to the topic of Personalized Cancer Treatment.

The URL is very simple: PersonalizedCancerTreatment.com
There, you'll find information about:

• Personalized Tumorgraft™
• Personalized Vaccine™
• Personalized Oncology Panel™

Image source: GSBTM