Most chemotherapies up until recently “poisoned” all rapidly growing cells in the body, both cancerous and non-cancerous. That’s why hair loss, nausea, vomiting, diarrhea, anemia and low white blood cell counts are commonly associated with chemotherapy. The side effects are caused by damage to normal cells that also grow rapidly like those in the digestive system and blood and hair cells.

New therapies for cancer treatment that are undergoing investigation by researchers include:

Molecular Targeted Therapies: Cancer cells grow and divide uncontrollably, develop a blood supply, and metastasize due to abnormal signals they receive inside the cell from proteins or enzymes. In cancer the normal protein and enzyme signaling pathways that regulate growth do not work properly because of genetic mutations in the cell.

An analogy often used is that of a car with the gas pedal stuck to the floor, the cells don’t stop growing and dividing when they should, the signal to grow is stuck in the “on” position and the protective mechanisms, the “airbags” and “antilock brakes” aren’t working. New research is directed to targeting abnormal protein and enzyme signaling pathways that cause cells to become cancerous. Different cancers have different signaling pathways based on different gene mutations, so the targets are different for different types of cancer.

An example of a targeted molecular therapy is the drug Gleevec. Gleevec targets a specific abnormal protein in cells of the cancer chronic myeloid leukemia. This cancer is caused by a defect in the Philadelphia chromosome, a genetic abnormality that causes the production of a cancer-causing protein molecule called BCR-ABL. Gleevec blocks this cancer-causing protein. Gleevec is taken in pill form and has few side effects, it does not involve receiving IV chemo through a port for hours in an office setting.

When Gleevec was being tested in an early clinical trial, the drug was only being tested to see if it was toxic to humans, not if it worked on the leukemia yet. But in the study, once a dose of 300mg was reached, all 31 of the 31 patients involved in the trial went into remission from their cancer. In a later study, 54 patients who had become resistant to all other forms of treatment for this leukemia were given Gleevec, and 53 responded. 5 year survival for those with this type of leukemia who are treated with Gleevec is now 95%. Prior to Gleevec, 30-50% of patients with this leukemia reached the advanced and often terminal stage of this disease in 3-5 years.

Some targeted therapies may be effective in more than one cancer if another cancer has a similar genetic mutation. Gleevec is also an example of this. Another cancer, a stomach cancer called GIST that had few treatment options but has responded well to Gleevec also.

Many other similar “targeted therapies” are currently under study and being developed. They have the potential to revolutionize cancer treatment.

Metastasis: 90% of cancer deaths are related to metastasis. If a cancerous tumors didn’t metastasize, in many cases cancer could be an easy disease to treat. Most of us with appendix cancer have been asked by someone in the general public “Well, can’t they just remove your appendix?”. For most of us that is almost never the answer, because appendix cancer has almost always metastasized into our abdomens by the time it is discovered. The metastasis is what has the potential to kill us, not usually the original tumor on the appendix. Some of the most fascinating lectures I listened to were those discussing molecular targeted therapies to prevent metastasis. Cancer that couldn’t metastasize would be a benign disease in many cases.

microRNA: micro RNAs are tiny segments of RNA that have just recently been discovered. Unlike other RNA segments in a cell that help transcribe proteins, these RNA segments function to turn genes “on” and “off”. In many cancer cells, mutated genes inappropriately turn “on” to manufacture proteins or enzymes that cause the cancer cells to grow out of control or to metastasize. Sometimes protective genes are wrongly turned “off”. Harnessing the power of microRNa could allow us to turn abnormal cancer genes “off” or protective genes that are not working “on”.

p53 Pathways: The p53 gene is the “guardian gene” in preventing cancer. It also functions through protein signaling pathways that initiate repair of abnormal mutations in a gene, or initiates the destruction of a mutated cell that cannot be repaired. In some cases when the P53 gene itself is mutated or does not function, molecular targeted therapies are being developed to enhance or correct the function and molecular pathways of a mutated P53 gene. Over 50% of those with cancer have a mutation of the p53 gene.

Biomarkers: in these studies, blood tests are being developed to identify cancers before symptoms or other tests can identify them. The goal is for these tests to be 100% accurate. Cancers caught in early stages are the most curable. Colon cancer caught early is 90% curable, but even in it’s early stage, there is an identifiably tumor. Biomarkers could allow cancers to be identified before tumors are even present so that progression can be stopped before the disease has a chance to cause harm. The goal is for the development of biomarkers that are 100% accurate.

Cancer Genomics and Personalized Cancer Therapies: In some cancer therapy, the majority of patients with a specific cancer respond to particular chemotherapies and medicines, while for others, the therapy has no effect. This is often related to subtle differences in the particular genetic mutations in an individual’s tumor. One scientist said even every breast cancer tumor is genetically different from another.

Personalized genomic cancer therapies in the future may involve genetic testing of a persons individual tumor when a biopsy is done, and identification of the particular genetic abnormalities in their own tumor. This would identify which specific targeted therapies would be effective for their particular cancer. This would prevent a patient from receiving and paying for a cancer therapy that would not be effective on their particular tumor and would allow the patient to receive the most effective treatment for their disease.

Chemoprevention: This could involve medications taken to prevent cancer in highly susceptible individuals. Currently some drugs like Tamoxifen are used to prevent recurrence in those with diagnosed breast cancer, but drugs could be developed to prevent cancer in those who have been identified to have abnormal genes that make them highly likely to develop the disease. I know a woman who’s family had a genetic predisposition to breast cancer. All of her female family members had died of breast cancer, so she had both of her breasts removed to prevent the disease in her own body. Chemoprevention may allow someone like her to take a targeted medication to prevent the disease without such radical prevention.

I’m sorry this post is so long, but I learned so much about so many avenues being pursued in cancer research at the AACR meeting. It was amazing. I have one last post to add to my series about my AACR involvement, rest your eyes in the meantime!