Combination Therapies and Personalized Medicine

Combination therapy combines two or more treatment regimes or cancer drugs to target cancer-related metabolic pathways in the cell.

Conventional therapies are more likely to fail because a single drug can only target one cancer-related pathway at a time. This often leads to the emergence of drug-resistant cancer cells during the course of treatment. On the contrary, combination therapy simultaneously targets different pathways and different cellular enzymes, thus reducing the chances of drug resistance.

The combination of different drugs also helps to lower their therapeutic dosage as well as increase the treatment efficiency due to a synergistic effect.

It also increases the cytotoxicity specifically in cancer cells while simultaneously reducing drug side effects on the normal cells. For example, caspase inhibitors can enter a normal cell and a cancer cell alike and inhibit apoptosis.

Similarly, the cytotoxic drug flavopiridol can induce apoptosis in both normal and cancer cells.

When both drugs are used together during therapy, the normal cells as well as cancer cells uptake both - caspase inhibitors and flavopiridol. In normal cells, both drugs cancel each other's effect, and the cell survives.

However, in the cancer cells, the overexpression of the ABC transporter selectively pumps the caspase inhibitor out of the cell, leaving behind the flavopiridol that induces apoptosis.

Cancer is a complex disease involving multiple genetic mutations and phenotypes that vary amongst patients as well as in different stages of the disease. Therefore, a patient-specific treatment may be more beneficial than one fit for all treatment.

Personalized cancer treatment is a precise approach that relies on the patients' genetic profile to guide the right therapy for more efficient cancer prevention and treatment.

For example, 15-20 percent of all leukemia cases are caused by a chromosomal translocation between chromosomes 22 and 9. It creates a fusion kinase protein BCR-ABL1 that triggers rapid cell proliferation.

Imatinib is a specific kinase inhibitor that inhibits the activity of BCR-ABL1 protein and slows down the growth of mutant cells. Genetic screening of leukemia patients for this particular mutation helps decide the use of imatinib in such patients and increases the survival rate.