Cancer evolves at
a staggering rate. Research is now being done to look into how the mechanism of
cancer cells evolve. More recently neoplasms have started to be looked at as
their own ecosystem and within this ecosystem different cells that are more and
less fit than the others. This new view could help researchers develop drugs
that prevent chemoresistance and reoccurrence.
There are drugs in the making
such as Imatinib that are trying to slow recurrence of neoplasms. But the amount
of progress they are making is questionable.
Figure 1:
"1.A. Recurrence-free survival for tumor size ≥3 and < 6 cm
1.B. Recurrence-free survival for tumor size ≥6 and < 10 cm
For small tumors there is little difference between the placebo and the drug on survival for 36 months and shortly after the survival rates are the same. With larger tumors the survival rate improves with Imatinib during the first 30-36 months, but after 36 months, the %recurrence-free and alive is almost the same as the placebo (within 8%). This is a noticeable difference, but a small one. One would hope that taking a treatment would lengthen your life more than three years. It would also be better if the difference between the placebo and Imatinib was more prominent. For example, for the medium sized tumors between months 31-41 the difference between placebo and Imatinib is almost not noticeable at all (~1%). For the drug to be more useful it should be substantially more effective in all types of tumors. An issue that brings the data’s validity into question is the sample size. The starting amount of patients for each type of tumor was between 292-179 patients. This is a good start, but I imagine for reliable data on medicine like this it would require information on thousands of patients and how they reacted to it, in order to get a better understanding.
Recent research has been done that
shows promise for the prevention of chemo resistant cancer cells. A study done
on metastatic colorectal cancer was done
to test the validity of using both Dasatinib (a Src inhibitor) and Curcumin (a
dietary agent with pleiotropic effects) to prevent recurrence by stopping
chemo-resistant cancer stem cells from coming back after chemotherapy (Nautiyal
J, Kanwar SS, Yu Y, Majumdar AP. Combination of dasatinib and curcumin
eliminates chemo-resistant colon cancer cells. Journal of molecular
signaling. 2011;6(1):7.).
They created colon cells that were
resistant to Folfox (common treatment for this cancer). After they compared the
amount of stem cell markers of the cells treated with placebo and the cells
treated with dasatinib and curcumin.
"Relative expression of various
colon cancer stem cell markers in chemo-resistant HCT-116 cells in response to
the exposure to dasatinib (1 μM), and curcumin (10 μM) for 3 days. The
controls represent the CR HCT-116 cells that were incubated with FOLFOX (50 μM
5-FU + 1.25 μM oxaliplatin) containing medium only. *P < 0.01, compared with
the corresponding control." (Source)
The results suggest that
dasatinib and curcumin noticeably reduce the amount of stem cell markers in
these colon cancer cells with as much as a 40% reduction in the relative
expression. These results are very promising but there are many things that
still need to be done. These cells were being treated for three days, so it is
impossible to tell if this will actually be beneficial to real patients, in a
situation were it could take months or years of treatment. Another area that
needs to be expanded on is the type of cell this works on. This figure
describes the reaction of HCT-116 colon cells only. There are many types of
colon cells and even more numerous types of other cells with differing
functions that need to be tested to see if this treatment works on them as
well.
In conclusion I think it
would be interesting to see how these two types of drugs could potentially interact.
If a chemotherapy like Imatinib, which has a relatively long (3 years) before
recurrence, was used in conjunction with the drugs dasatinib and curcumin (which
reduce the cancer stem cells ability to reproduce and cause recurrence after
treatment), than maybe a new type of drug cocktail could be created that would
stop recurrence from happening.
Works Consulted
Merlo, L. M. F., Pepper, J. W., Reid, B. J., & Maley, C. C. (2006). Cancer as an evolutionary and ecological process. Nature, 6, 924-935.
Nautiyal J, Kanwar SS, Yu Y, Majumdar AP. Combination of dasatinib and curcumin eliminates chemo-resistant colon cancer cells. Journal of molecular signaling. 2011;6(1):7.
