The Human Cancer Genome Project - Moving Cancer Research to a New Level

Friday, September 23, 2005

The Human Genome Project was a landmark collaborative study to map the entire human genome, that is read all the millions of letters of genetic code that make a human.

The project, funded by the US government ended officially in 2003, achieving its goal. The data produced will occupy scientists for decades to come.

Because cancer is fundamentally a genetic disease, either a mutation that a person was born with or a mutation caused by some environmental factor, like asbestos triggering mesothelioma or lung cancer, understanding the underlying genes, gene products and cellular pathways is critical to moving cancer research forward. Even when there are environmental factors, an individuals genetic makeup determines if cancer will develop. Even powerful carcinogens will not induce cancer in some individuals. One only needs to look at all the 90+ year old smokers for an example. It is likely that if someone has been smoking heavily for 75 or more years, the particular carcinogens in their cigarettes will not cause cancer. The reasons could be many, but are fundamentally genetic. Perhaps they produce an enzyme that deactivates the carcinogen or perhaps they have a particularly robust cellular control mechanism that keeps all precancerous cells in check.

In February of this year a government working group published a paper titled Recommendations for a Human Cancer Genome Project. In this paper they spelled out the many benefits that would emerge from such a project. The goal would to obtain a comprehensive understanding of the genetic basis of human cancer.

In the report they cite recent advances in cancer treatment that were made possible because of greater understanding of the genetic and molecular processes.

One example is a type of lung cancer called Lung Adenocarcinoma and treatment with a drug called gefitinib (Iressa).

Genetic studies of patients with Lung Adenocarcinoma found that 5-10% of patients of European descent and 25-30% of Japanese patients had a particular mutation in the EGFR gene. This gene makes a protein growth factor that the tumor needs for growth. People with this mutation have a dramatic response to Iressa, while the majority of patients show no effect. Iressa failed to win FDA approval because it showed no significant benefit in general trials. By targeting patients with only this mutation the drug would most likely have shown a dramatic effect.

Genetic studies are the wave of the future in cancer research. They will improve the selection of molecular targets for treatment, allow for faster and smaller clinical trials and identify markers for early detection.

To accomplish this project the researchers will collect 250 tumors for sequencing from each of the top fify types of cancer, this includes mesothelioma. This will allow the detection of unusual genetic types that exist at 5% or great in frequency.

Here's some of the numbers they're working with:
Cancer Types and Subtypes

Incidence in United States >100,000 cases/yr
Prostate cancer 230,110
Breast cancer 217,440
Lung cancer 173,770
Colon and rectal cancer 146,940

Incidence in United States >10,000 cases/yr

Bladder cancer 60,240
Melanoma 55,100
Non-Hodgkin’s lymphoma 54,370
Cancer of the uterus 40,320
Cancer of the head and neck 38,530
Kidney and renal pelvis 35,710
Cancer of the pancreas 31,860
Cancer of the ovary 25,580
Thyroid cancer 23,600
Cancer of the stomach 22,710
Liver and intrahepatic ductal cancer 18,920
CNS tumors 18,400
Multiple myeloma 15,270
Cancer of the esophagus 14,250
AML 11,920
Cancer of the cervix 10,520

Incidence in United States >1000 cases/yr
Testicular cancer 8,980
Soft-tissue sarcomas 8,680
CLL 8,190
Hodgkin’s disease 7,880
Gallbladder and other biliary 6,950
Cancer of the small intestine 5,260
CML 4,600
Anal cancer 4.010
Cancer of the vulva 3,970
ALL 3,830
Ureteral cancer 2,450
Sarcomas of the bone 2,440
Cancers of the eye and orbit 2,090
Cancer of the urethra and penis 1,570

mesothelioma looks like its lumped in with lung cancers. The goal is to get a sample from each of the major subtypes of the above cancers. As collection begins we should make sure that mesothelioma is a distinct category with the full complement of 250 samples.

The project is proposed to have a budget of 150 million dollars a year over 9 years. They propose starting the project in mid 2006.

In July members of the scientific community met to discuss the many technological and logistical challenges that such a large scale project presents. Both the National Cancer Institute and the National Human Genome Research Institute have committed 50 million dollars to get the project off the ground.

This is a very exciting time in cancer research. The knowledge gained from such a large project will impact human health for centuries to come. In the near term we will probably start hearing more about genetically targeted therapies and hopefully a few magic bullets.