Question

1.Review how patients who might benefit from Targeted therapies are identified.
2. Select one currently approved targeted therapy and describe it's mechanism of action and which cancer it is used to treat.
Include the reference.

Answer 1

Target therapies are different from the conventional chemotherapies. Chemotherapies work on the principle that cancer cells divide and grow quickly that healthy body cells and target on the dividing cells. But the side effect of the chemotherapy is that it can also eliminate the healthy proliferating cells of our body.

Target therapies explore the differences in the metabolism and the genetics of healthy cells and cancer cells, and thus targets these differences. For example, if a cancer cell overexpresses some protein or some receptor than the normal healthy cells can be targeted through the therapy.

We can compare the gene expression of a healthy person, a cancer patient, and a patient underwent targeted therapy by following ways:

1. For example, a particular cancer cell overexpresses a protein on its cell surface. So, by performing different assays using techniques such as microarray we can check the protein expression level.  

• healthy person's protein expression will be taken as control
• overexpression of protein will show the cancer patients protein expression.

And if the treated patient shows lower expression of protein than the cancer patient and the protein expression is near about normal, we can state that the patient has benefited from target therapy.

2. Target therapies are of two types:

1. monoclonal antibodies
2. small molecule drug

There are targeted therapies approved for many cancers like breast cancer, colorectal cancer, lung cancer, melanoma etc.

Recently ivosidenib has been approved by the FDA against relapsed or refractory acute myeloid leukemia (AML) in adults.

This drug which is used in target therapy is a mIDH inhibitor.

mIDH is a metabolic enzyme isocitrate dehydrogenase 1 which undergoes somatic point mutation within its active site at Arginine 132 (R132) resulting in gain of function in the cancer cell.

This mutated mIDH the produces D 2-hydroxyglutarate, competatively inhibit 2 Ketoglutarate dependent dioxygenase enzyme which lead to inhibition of normal cell differentiation process.

REFERENCE- FDA government approved drugs.