Personalized Cancer therapy in Hilly Clinic

Tailor made health care and treatment

Genetic and genomic profile of each human being is unique. About 0.5% of DNA sequence of genome of human beings is different from each other. This difference in genetic sequence (so called “SNP”) decides difference of each people, for example, color of skin, eye, height, etc. It also decides how each individual reacts to diet, environment and drug.

For example, regarding diet and nutrition, we know that omega-3 is good and protects from a lot of diseases (such as cardiovascular diseases). However, depending on genetic profile of each people, some people (e.g. with specific genotype of ALOX5 gene) actually show higher risk of developing cardiovascular diseases if they are given too much omega-3.

Some people show decrease of body weight with exercise, but others never lose weight despite exercise, for whom diet and calorie restriction is mandatory. These examples show that tailor made diet/ life style/ exercise care depending on genomic test of each individuals is mandatory to make human beings healthy and live long time.

Regarding disease, for example, cancer, each cancer is different from each other. Cancer is the uncontrolled growth of abnormal cells. Genetic tests for targeted cancer therapy detect mutations (changes) in the DNA of cancer cells. Some of these genes are involved in controlling cell growth and maturation. Knowing whether the cancer has a particular mutation in the gene can help guide the type of treatment that a person receives. The presence or absence of certain mutations can predict who may benefit from certain drugs and who is not likely to respond. Medical researchers have long studied these changes in genes in order to better understand cancer and to develop drugs to fight it. Their goal has been to create drugs that disrupt a specific step in cancer growth, while doing minimal damage to normal cells. These are called targeted drugs or targeted therapy. What researchers have noted is that specific types of cancer are frequently associated with specific genetic mutations. Not every cancer will have them, but a significant percentage will, and cancers with these mutations usually have a more predictable response to certain drug treatments compared to cancers without these mutations.

Lung cancer is different from colon cancer. Lung cancer of patient A is different from that of patient B. Cancer cells in same patient are also different depending on whether they are in lung or spread to bone or brain. Even cancer cells in same location (e.g. lung) of same patient are composed of so many different clones. Each clone of cancer cells act differently to chemotherapy. This is the reason why doctors fail by blind chemotherapy (i.e. chemo drugs are given in combination and in high dose even without knowledge they are effective and more importantly safe) and fail again even after success by initial chemotherapy. These show need of genomic test which can guide adequate, tailor made chemotherapy of advanced cancer. Thus, these are the modalities we suggest based on the tests we run even before the patient arrives based on paraffin-embedded blocks of cancer tissue we acquire even before the patient comes in.

(GROUP 1 TREATMENT MODALITIES) Tailor made drug therapy by using conventional chemo drugs selected by gene test. These drugs will be purchased from drug companies in USA and, if possible, be administered in a way that it can be reimbursed by insurance in USA. 

• Genetic tests to detect the presence of mutations in cancer tissue that tell a healthcare practitioner whether the person being tested is likely to benefit from a specific therapy

(GROUP 2 TREATMENT MODALITIES) Tailor made drug therapy by using molecular targeting drug & targeted antibodies. such as erbitux, avastin, herceptin, iressa, tykerb, etc.

• Cancer drugs that inhibit or target very specific proteins associated with certain cancers (Two examples are tyrosine kinase inhibitors and epidermal growth factor receptor (EGFR) antibodies.)

 (GROUP 3 TREATMENT MODALITIES) Native immune cell therapy, including natural killer (NK) cell and NK/T cell or cytokine induced killer (CIK) cell.

 (GROUP 4 TREATMENT MODALITIES)  Adaptive immune cell therapy, including dendritic cell and CAR-T cell. 

 (GROUP 5 TREATMENT MODALITIES) Genetic vaccines  

(GROUP 6 TREATMENT MODALITIE) Cytokine gene drug

 (GROUP 7 TREATMENT MODALITIES) Tumor suppressor gene drugs 

(GROUP 8 TREATMENT MODALITIES) other treatment methods not included above. 

  These include stem cell therapy, radiation therapy, surgical therapy, special means of gene therapy such as antisense gene therapy, etc. 

Type of Cancer

Gene Tested*

Interpretation of Test Result

Breast cancer

Her2/neu

When present, likely response to trastuzumab

Chronic myelogenous leukemia (CML)

ABL1

Nonresponsive to imatinib when mutation(s) present

 

BCR-ABL

When present, can be measured periodically to monitor response to targeted drug

Colon cancer

KRAS

When mutation present, likely resistance to tyrosine kinase inhibitor

 

BRAF

Poor prognosis when mutation present

Gastrointestinal stromal tumor (GIST)—rare tumors of the digestive tract

KIT

Depending on mutation present, better response to imatinib therapy, increased dose of imatinib likely necessary and better response to sunitinib, or possible resistance to imatinib

 

PDGFRA

When mutation present, less likely to respond to imatinib

Melanoma

BRAF

Better response to vemurafenib when mutation present with metastatic melanoma

Myeloproliferative neoplasms (MPNs)

JAK2

When mutation present, may be measured periodically to monitor responsiveness to treatment (e.g., Ruxolitinib)

Non-small cell lung cancer (NSCLC)

EGFR

Best response to tyrosine kinase inhibitors such as gefitinib and erlotinib in those with certain mutations

 

EML4-ALK

If ALK is present, may respond to ALK kinase inhibitors, such as crizotinib

 

ROS1

If ROS1 is present, ALK kinase inhibitors, such as crizotinib

 

KRAS

Poorer prognosis when certain mutations present, resistance to tyrosine kinase inhibitors, and poor response to platinum/vinorelbine therapy

 

PDL1

Likely response to immunotherapy

Cancers of unknown origin—cancers detected in unusual body sites and thought to have spread (metastasized) from another location

Several genes evaluated together (genomic array or profile)

Helps determine the organ or body part in which the cancer originated in order to help guide treatment

Q & A

1. Should everyone with cancer have genetic testing performed?
Testing is only required if a patient has a specific type of cancer for which targeted therapies have been identified as being useful and the health care practitioner is considering starting the patient on one of these therapies.
2. Can I receive one of these therapies and still not benefit from it?
Yes, most people whose cancer matches up with the “likely to benefit” criteria will respond, but a percentage will not. Each person and each cancer is different.
3. Can I take a targeted therapy drug without being tested?
In most cases, this is not recommended. The drugs have been developed with specific associations and your cancer is not likely to respond if you do not meet the identified criteria.
4. Can molecular testing be performed in my healthcare provider’s office or my local hospital laboratory?
Testing requires specialized equipment and is not offered by every laboratory. In most cases, samples will be sent to a reference laboratory.

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