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].