Molecular cancer genomics
There are many types of cancer that appear the same in traditional pathology and we are also becoming aware of tumour heterogeneity, or genetic diversity within a single cancer. This discovery poses the possibility of discovering that drugs that do not work in general populations of cases might be effective in cases with particular genetic profiles.
Oncogenomics, or ”Personalized Onco-genomics”, is the application of personalized medicine to Cancer Genomics. To better understand disease pathology and improve drug development, high-throughput sequencing methods are used to characterize genes associated with cancer. Among the areas of genomics with the greatest potential are oncogenomics, particularly for drug therapy.
Examples of this include:
A monoclonal antibody drug called trastuzumab (trade name Herclon, Herceptin) targets the HER2/neu receptor. It is used primarily in the treatment of breast cancer. Patients are prescribed this drug only if their cancer contains an overexpression of the HER2/neu receptor[22].
Patients are screened for potential benefit from Herceptin treatment based on two tissue-typing tests. Several tissue tests are performed, including immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH). Patients with Her2+ status will receive Herceptin therapy (trastuzumab)[23].
Gleevec (imatinib) is a tyrosine kinase inhibitor developed to treat chronic myeloid leukemia (CML), in which the BCR-ABL gene (a result of a reciprocal translocation between chromosomes 9 and 22) is present in over 95% of cases and produces hyperactivation of abl-driven protein signaling. Based on scientific knowledge of disease pathophysiology, these drugs inhibit the Ableson tyrosine kinase (ABL) protein specifically[24].
Genes identified in tumor biopsies assist in recommending specific drugs associated with immunotherapy response, and specific mutation patterns are linked with previous exposure to cytotoxic cancer drugs [25].
While lung cancer has limited systemic treatment options, targeted treatments are becoming more common. Many new drugs and compounds, such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors, are being developed and approved. More than 70% of these drugs work against epidermal growth factor receptors (EGFRs) [26]. We investigated the pharmacokinetics of targeted drugs, which enabled us to develop new medicines and predict radiolabelled drug binding to tumours. Immuno-PET is primarily used to detect antigens. Immuno-PET has been studied with MAbs, and mAbs have been labelled with radionucleoids such as 89Zr [26].
Melanoma survival rate is just 15-20 percent when it is spread to other parts of the body. About 50 percent of melanomas contained a mutation in the BRAF gene which plays an important role in the overproduction and spread of cancer cells[27]. Based on this information three immunotherapy anticancer drugs are developed which function by inhibiting proteins that prevent the immune system from destroying cancer cells [28].
A new wave of molecularly targeted therapies has transformed chronic myeloid leukemia (CML) from a highly lethal disease into a disease in which patients can live normal, healthy lives. Drug imatinib targets the abnormal proteins that signal cancer cells to divide. Imatinib works by stopping these signals. CML patients now live lives that are similar to the average as a result of the availability of more drugs in this class [29].