Guest Author - Adelle Ottavini
This drug resistance phenomenon in cancer is one of the trickiest aspects for scientists in the cancer battle. One fact to bear in mind is that each cancer is unique in having different biochemical and cytogenic profiles. Often, in the same tumour, the cancer cells will be similar but not identical – some sensitive to a given drug, and others not. The resistant cells can divide and multiply!
The reasons why drug resistance materialize are complicated. In some cases some of the cancer cells undergo gene mutation (modifying the version of the gene). The chemo will eliminate the ‘normal’ cancer cells, but miss the gene altered cells. These altered cells can then multiply, and often become even more resistant to the given chemo. Another reason can be the size of the tumour. In very large tumours, the blood supply in/towards the centre of the tumour is poor – making targeting of the chemo difficult. This is especially the case in brain tumours. Another reason is an occurrence called MDR1 – the amplification of a gene. These genes have transmembrane proteins (p-glycoprotein) that either stops the drugs from entering the cell, or ejects the drugs from the cell.
In breast-and ovarian cancer, the problem could be the loss of the oestrogen receptor in ER+ (the most common and most treatable form of breast cancer). This means that the cancer cell doesn’t depend on oestrogen as a growth stimulant anymore, almost becoming like ER-, the more difficult type to treat. Using tamoxifen (the general hormone therapy treatment) will thus fail, and different chemotherapy treatments will be used. Sometimes, in breast cancer patients using tamoxifen, the protein Pax2 that must keep the ‘switch’ in the HER2 gene off (thus keeping it blocked) – sometimes fails. In this case a change of drugs will also be necessary. Scientists have also noted that a faulty BRCA2 gene – necessary for repairing faulty DNA – can re-activate itself, allowing cancer to repair its own damaged DNA! Research on this faulty gene is currently being done. In the meantime 7 other genes that form signalling pathways for cancer have been discovered in ER+ patients. The presence of these genes can also make the use of tamoxifen fail.
Drug resistance in cancer warrants further clinical studies and much are being undertaken. Scientists in Tel Aviv University discovered that the use of Prozac (fluoxetine) most certainly blocks the drug doxorubicin from leaving the interior of cancer cells up to 1000%. This finding is worth a celebration! Scientists in Florida and China are investigating the use of gold nanoparticles (nanotechnology) to identify p-glycoprotein on cancer cell surfaces. By identifying p-glycoprotein on cells before treatment begins, doctors can assure the correct treatment being given from the very beginning. This should promise far less disappointment amongst patients and doctors during the course of managing the cancer. Another finding is that by doing aneuploidy (numeric aberrations in chromosomes) screening (under a microscope) at the diagnosis of cancer, the correct drug could be chosen from the start. ‘Diploid’/normal cells have 23pairs/46 chromosomes. In solid tumours there are up to 90 chromosomes – making them ‘aneuploid’/abnornal. It is still debated whether aneuploidy is a consequence or a cause of cancer.
The main aim for cancer patients, there caregivers and scientists are to successfully reach apoptosis – the death of cancer cells. The days of drug resistance are hopefully now coming to its own ‘suicide’!
