Louisville Medicine Volume 68, Issue 11 | Page 14

PRACTICAL GENETICS
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and prostate cancers .
The presence of certain mutations in certain cancers can be associated with better or worse outcomes in response to therapy . For example , patients with acute myeloid leukemia ( AML ) with a mutation in the FLT3 gene have a poorer prognosis than patients without this mutation , requiring more intensive treatment including hematopoietic stem cell transplant .
Similarly , mutations in the P53 and Rb genes in many cancers are associated with poor prognosis . On the other hand , AML patients with NPM1 gene mutation ( in the absence of other defects ), non-small cell lung cancer patients with certain EGFR / ALK / ROS mutations are known to have overall better prognosis requiring less intensive treatment .
Newer genetic tests , called gene expression panels , look at multiple genetic defects to predict the risk of cancer relapse after treatment . These are now available for some of the solid organ cancers including breast , colon and prostate cancers . Out of these tests , the 21 gene panel assay in patients , commonly known as the Oncotype Dx ® breast cancer assay for patients with hormone receptor-positive breast cancer , is most commonly used in clinical practice . It ’ s helpful in predicting benefit from chemotherapy in addition to hormone therapy for these patients .
Genetic information in cancer patients carries an increasing role in treatment decisions . Molecular targeted therapies and immunotherapy have gained a significant foothold in the management of almost all types of cancers at various stages . Targeted therapy uses drugs to target specific genes and proteins that are involved in the growth and survival of cancer cells . Usually , the target is a protein coded for by a gene which has undergone mutation in some form . Once this mutation is identified , the drugs targeting either that specific mutation or the protein can be developed . The most commonly used targeted drugs are in the form of monoclonal antibodies or small-molecule drugs .
Some examples of extremely effective targeted therapies include Trastuzumab targeting the Her2 mutation in breast cancer , Imatinib targeting the BCR-ABL mutation in chronic myeloid leukemia
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( CML ), Osimertinib targeting the EGFR mutation in lung cancer , and Dabrafenib targeting the BRAF mutation in melanoma and other cancers .
Immunotherapy drugs utilize the specific genetic expression inside cancer cells and various immune cells to help the immune system fight the cancer . They release the brakes on our immune system to attack cancer cells . These immune-checkpoint inhibitors have revolutionized cancer therapy in many cancers such as melanoma , lung , kidney and bladder cancers .

The known association between certain hereditary cancer syndromes and genetic mutations can be helpful to assess the risk of a particular cancer in family members of a patient . Genetic testing is now available for a number of rare hereditary cancers especially those associated with single gene disorders .

One of the more recent advances targeting genetic alterations associated with cancer is CAR-T therapy which uses T-cells , the patient ’ s own immune cells , to search out and destroy leukemia and lymphoma cells . The process involves first removing , then reprogramming these cells . These T-cells are re-programmed to identify , then kill , the patient ’ s cancer cells , in children and adults with all and also patients with some types of Hodgkin ’ s and non-Hodgkin ’ s lymphoma . Stem cell therapies aim at replacing abnormal / mutated cells with cells having a “ new normal ” genome . An antitumor vaccine known as Sipuleucel-T has recently been approved for advanced / unresectable prostate cancer . This is designed to work through antigen-presenting cells to stimulate a T-cell immune response targeted against prostatic acid phosphatase ( PAP ), an antigen that is highly expressed in most prostate cancer cells .
We have learned a lot about how genetic changes affect cancer development . This knowledge has led to improvements in cancer care , including earlier detection , risk reduction , the use of targeted therapy and survival . However , many cancers are not linked with a specific gene and likely involve multiple gene mutations . Moreover , some evidence suggests that genes interact with their environment . This further complicates our understanding of the role genes play in cancer . We need many more resources devoted to research , pharmacogenetics and the invention of effective gene therapy for as many cancers as possible .
Dr . Singh is a practicing oncologist at UofL Health - James Graham Brown Cancer Center .
Dr . Sidhu is a first-year fellow at the UofL Department of Medical Oncology & Hematology .