Archive for April, 2013
An anti-diabetic drug to fight cancer? Metformin use associated with greater survival in Ovarian Cancer patents
22 April 2013
Today I came across a very interesting case-control study by Kumar et al. on the effects of metformin on the outcomes of ovarian cancer patients.
This study piqued my interest for a couple reasons. Metformin is already used in the clinic, is widely available, inexpensive, and its side effects are well-documented. It is taken orally, not intravienously, which makes administration less stressful for patients. Existing drugs that can be re-purposed as anti-cancer drugs are of great interest for another reason: time and money. If Yours Truly identified the achilles heel of all cancer tomorrow (a highly unlikely event) developing a drug to exploit this hole in the armor might take as long as 10-17 years and cost upwards of $800 million to develop and test a new drug (source).
There is also the phenomenon of physicians being hesitant to prescribe new therapies or drugs that they are unfamiliar with. A re-purposed drug might get quicker recognition and use in the clinic than a brand new drug.
I guess what I’m trying to say is that if a drug like metformin could be re-purposed to fight cancer, it would have immediate clinical impact treating a very, very nasty disease: ovarian cancer.
So, what does Metformin do? Well, that’s actually a very good question. It’s such a simple compound that it’s pretty much impossible to know all of its effects, but it’s best-known effect is to suppress hepatic gluconeogenesis, or the production of glucose in the liver, that gets released into the bloodstream. This is a boon for Type II diabetic patients in particular, and Metformin is a widely used anti-diabetic drug. In the United States, over 48 million prescriptions were filled in 2010 (source).
Recently, it has come under interest as a potential anti-cancer drug as a result of several studies carried out in the lab, but not in people.
The authors were curious if patients that had ovarian cancer and were also receiving metformin might fare better than those that were not on metformin. The authors identified 72 ovarian cancer patients who were diabetic and on metformin, 103 diabetic ovarian cancer patients not on metformin, and 178 ovarian cancer patients who were neither diabetic nor on metformin. The results were rather striking:
RESULTS: In a preliminary analysis of the OC cohort (72 cases and 143 controls), cases had better survival (5-year disease-specific survival for cases vs controls, 73% vs 44%; P . .0002). In the definitive analysis of the EOC cohort (61 cases and 178 controls), the distribution of age, disease stage, optimal cytoreduction, serous histology, and platinum chemotherapy remained similar between cases and controls (P > .05). Despite these similarities, cases had significantly better survival (5-year disease-specific survival for cases vs controls, 67% vs 47%; P . .007). On multivariate analysis, metformin remained an independent predictor of survival (hazard ratio, 2.2; 95% confidence interval, 1.2-3.8; P . .007) after controlling for disease stage, grade, histology, chemotherapy, body mass index, and surgical cytoreduction.
I would like to stress that five years after diagnosis, ovarian cancer patients that had been prescribed metformin were 30% more likely to still be alive.
The dose and duration of metformin used by these patients varied widely, and it is very possible that metformin might be even more effective than shown in this study if dosage and use is further refined. But, we must be careful: this is merely a case-control study. The golden standard is a controlled clinical trial with a placebo group. As it just so happens, there is a large scale clinical trial investigating metformin use in breast cancer (National Clinical Trial identifier NCT01101438). I will follow the results of this clinical trial with great interest!
7 April 2013
Good morning, dear readers. I was in lab sipping coffee and updating notebooks this calm Sunday morning when I stumbled across this beautifully clear, enlightening, and inspiring, if not haunting, glimpse into the consciousness of author Susan Gubar, currently battling ovarian cancer:
NT Times: Living With Cancer: Truthiness
Reading it coalesced what were otherwise fleeting ideas floating around my head. Although not completely science related, I have always been fascinated by the different ways patients deal with the prospect and uncertainty about their own mortality. After all, the aim of all cancer research (and this blog) is to reduce human suffering.
Can perspective reduce suffering even in the most dire of circumstances? What if we realize that they are not so dire to begin with? What if this process of death enables us to LIVE? For those of us not stricken with cancer, can we learn from these lessons without going through the disease ourselves? For those fighting the disease, could we develop a framework for a standard procedure of mental conditioning and consultation for mental clarity and greater quality of life?
Image: if we accept that the horizon is hard to see, perhaps we can gain more out of the present, whether we have cancer or not?
I realize that these are open-ended questions, but as I have progressed in my scientific apprenticeship I have come to realize that embracing these types of mental uncertainty can yield unexpected enlightenment, and yes, it can sometimes provide very concrete solutions to daunting physical, highly technical biological problems.
Even if I could waive my magic pipette and cure all cancer tomorrow, it would not alleviate human suffering. The absence of physical illness is not health. At the same time, I think there are very legitimate lessons that everyone can learn from cancer patients.
Recently, NPR did an article (Death Cafes Breathe Life Into Conversations About Dying) about people who meet up, have tea, sit around, and talk about dying! It might seem initially repulsive or taboo, but what has developed out of it is something that this cancer researcher sees as great value:
“When we acknowledge that we’re going to die, it falls back on ourselves to ask the question, ‘Well, in this limited time that I’ve got, what’s important for me to do?’ ” Underwood says.
Perhaps being more open about our own mortality will help us put more value in the time that we have left. We are all going to die at some point. (unless science conquers aging, which is a possibility, but I am not holding my breath) I cannot help but notice that most of my conversations with people about cancer revolve around an individual’s deep-seeded fear of dying. It’s extremely consuming; I’m willing to bet that more people will suffer from crippling cancer anxiety than the disease itself. Neither is pleasant. One is almost certainly curable.
Almost all cancer research is directed at extending life. I seldom hear anything about enhancing the time living for cancer patients. And not just cancer patients; I see great value in this for all of us. How could we cultivate this as individuals, as communities, and as a society?
Anyway, I must get back to work, dear readers. Thank you for taking the time to hear my thoughts. I would love to hear yours!
2 April 2013
What happens when it’s impossible to tell where the cancer came from?
This morning I attended a great discussion at a bi-weekly meeting known as: Tumor Board. Oncologists will present difficult or interesting / unusual cases of patients they are seeing: diagnoses, observations, treatments, caveats with various forms of new therapies or diagnostic techniques, etc.
Most cancers are categorized by the organ of origin. Think: “breast cancer” or “lung cancer.” Although a “breast cancer” might spread to the lungs, it is still known as a “metastatic breast cancer” not a “lung cancer.” The way that metastatic breast cancer to the lungs is treated most effectively more closely mirrors how “breast cancer” is treated, not “lung cancer.” The organ of the tumor of origin often gives a good proxy for therapies appropriate for a cancer that has spread from that organ as well.
But, what happens when one cannot identify the tumor of origin? Many cancer patients are not diagnosed until cancer has begun to metastasize or spread, and it’s not always obvious from where the cancer originated, especially if tumors are in multiple organs. In the last two decades oncologists have begun to use a panel of protein markers as ways to classify and stratify cancers for appropriate therapy guidelines. For example, it’s possible to differentiate a metastasized breast cancer to the lungs from a lung cancer using specific protein markers for breast cells.
Although it was a big step forward from microscope-based histological assessment alone, the guidelines do not always reflect the underlying biology, and the underlying gap in the particular cancer’s armor.
I’ve discussed this a bit before, but before long it might be possible that all cancer patients have their tumor genome sequenced. In theory, this WOULD reveal all genetic changes that underly an individual’s disease, immediately suggesting the most effective therapy to use with the smallest side-effects. Our traditional means of classifying tumors might become trivial and/or obsolete.
Such a future practice might alleviate problems with identifying the tumor of origin. Going back to tumor board, there was a case of a poor woman that had painful tumors in her abdomen with no obvious organ of origin, and protein markers used were not able to classify it further, either. The oncologists debated about what course of action to take, and were unsure about the most effective chemotherapy regiment.
At that moment I thought about the genomic tools on the horizon and what that might mean if the woman had been diagnosed in, say, 5 or 10 years?