Innovative Gene Therapy for Colorectal Cancer: Viral Vectors and Precision Medicine

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• Gene Therapy for Colorectal Cancer
• Trojan Horse Strategy in Cancer Treatment
• Viral Vectors and Lethal Genes
• Precision Medicine Platform for Cancer
• HIV Enzymes in Cancer Therapy
• Future of Cancer Gene Therapy
• Full Transcript

Gene Therapy for Colorectal Cancer

Dr. Nadir Arber, MD, is pioneering gene therapy for colorectal cancer using viral vectors. This experimental treatment is aimed at terminally ill patients, offering a last resort when other therapies have failed. The approach involves delivering therapeutic genes directly to cancer cells, providing a targeted and potentially more effective treatment option.

Trojan Horse Strategy in Cancer Treatment

Dr. Arber describes the "Trojan horse strategy" as a novel method to combat cancer. This technique exploits cancer's own growth pathways to introduce lethal genes into malignant cells. By targeting pathways unique to cancer cells, this strategy aims to halt tumor growth while minimizing damage to healthy tissue.

Viral Vectors and Lethal Genes

Viral vectors are used to deliver lethal genes specifically to cancer cells. Dr. Nadir Arber, MD explains that these vectors are engineered to express antibodies that recognize cancer-specific markers, such as CD24. This ensures that the therapeutic genes are activated only within cancer cells, sparing normal cells from harm.

Precision Medicine Platform for Cancer

This gene therapy approach represents a precision medicine platform that can be tailored to individual patients and tumor types. Dr. Anton Titov, MD, emphasizes the adaptability of this strategy, which allows for customization based on the genetic profile of the cancer, potentially improving treatment outcomes.

HIV Enzymes in Cancer Therapy

Dr. Arber is also exploring the use of HIV enzymes, specifically integrase, in cancer therapy. This innovative approach involves using the enzyme to create DNA breaks in cancer cells, triggering an immune response that leads to cell death. This method leverages the body's natural defenses to selectively target and destroy cancer cells.

Future of Cancer Gene Therapy

The potential of gene therapy to revolutionize cancer treatment is significant. Dr. Nadir Arber, MD, and Dr. Anton Titov, MD, discuss the promise of these cutting-edge therapies to change the landscape of oncology. By harnessing the power of precision medicine, gene therapy offers new hope for patients facing difficult prognoses.

Full Transcript

Dr. Anton Titov, MD: Gene therapy as a magic bullet against cancer captures the imagination. But progress has been slow. Leading cancer expert and researcher shares new ideas on subverting viruses to treat tumors.

Dr. Anton Titov, MD: You work also on the gene therapy for treating colorectal cancers. You use viral vectors. Could you discuss your gene therapy work in colorectal cancer?

Dr. Nadir Arber, MD: Yes, you just have to emphasize that this is still experimental. This week we are going to do gene therapy on the first colon cancer patients. We're going to give gene therapy for terminally ill cancer patients. It's like mercy therapy. We are going for the last resort of mercy because some colon cancer patients are otherwise going to die.

Dr. Anton Titov, MD: The patient has nothing to lose. It's a lot of hope. But gene therapy for colon cancer expectations are very much conservative. This is, again, we're trying to think outside of the box.

Dr. Nadir Arber, MD: Sometimes you have normal cells turn into malignant cells. They usually have some mutations. One mutation is KRAS. Cancer cells constantly divide and become cancer. It's not controlled divisions, very basically.

With chemotherapy or additional cancer therapy, we are trying to stop these active molecular pathways. They turn normal cells into malignant cells. Usually, cancer therapy leads to tumor growth arrest. Cancer cells stop growing because this active cancer growth pathway was shut down.

Then after a while, the cancer finds some other growth-enabling pathways. Cancer growth bypasses this molecular pathway stop that was put into cancer. Now cancer resumes activity via other different molecular pathways. Usually, we have seen in a clinic. After cancer growth started again, then all of a sudden there is a rapid deterioration. The colon cancer patient dies quickly.

What we tried in my lab is to use a different cancer treatment. I call it the Trojan horse strategy. Instead of inhibiting these active cancer growth pathways that exist only in cancer cells, we are using cancer growth molecular pathways to specifically kill colorectal cancers.

What you use is the strategy that has five components. First, you have to identify these active cancer molecular pathways. Then you have to identify where the cancer pathway attaches to the nucleus. It is the DNA responsive elements. Sometimes cancer growth message comes from the membrane into the cytoplasm. Then the cancer message goes into the nucleus. It is telling the cells to divide.

We can hook to it, you can identify it, and we can hook a lethal gene to the message. It is going to be activated only in the cancer cells and not in the normal cells. In order to improve the strategy, we are using usually viruses to deliver a lethal gene construct into the cancer cells.

We want to selectively bring the gene therapy only to cancer cells. We are expressing on the top of the viruses specific antibodies to CD24. It is, as we spoke before, expressed in malignant cells but not in normal cells. The final component is that we are expressing very lethal genes that are based on the active cancer growth pathway.

We also have the antidote that is regulated by tumor suppressor genes. They are expressed in the normal cells but not in the malignant cells. We can keep the balance of just killing the colorectal cancer cells. As we know, there is also some "leak" in any biological system. We can express antitoxins in the normal cells. In that way, we can use even higher doses of gene therapy to selectively kill colorectal cancer cells. But at the same time, we make sure that healthy cells are going to stay alive.

Dr. Nadir Arber, MD: This is very promising gene colorectal cancer therapy. What is good about it? This is a gene therapy platform for many types of cancer. It's not just for any specific cancer. Because using this gene therapy strategy, you can change every part of it. You can adapt cancer gene therapy to the person or to the tumor. This is precision medicine at its best. It is very promising.

We are looking into the future. This may change the landscape of cancer therapy. And that's clearly the goal of every clinician and clinician-scientist. Absolutely!

Another cancer therapy clinical trial that we are doing now. It's taken a new medication that is used to treat HIV patients. It's using the integrase of the HIV virus. We are using this technology to treat cancer. It is a cancer therapy clinical trial we are starting now. It looks very promising.

Dr. Nadir Arber, MD: This is how we are using some viruses that were developed in my lab as cancer therapy. We specifically target cancer cells, and only the cancer cells. Viruses bring this integrase enzyme. It is causing cuts in the DNA. When there are a lot of cuts in the DNA, the immune system is going to recognize these cells as cancer cells. Immune cells will execute the program of cell death, apoptosis. That selectively kills cancer cells.

This is a fascinating new cancer therapy. That is thinking "outside of the box." Cancer gene therapy might give another hope for cancer therapy. This is certainly interesting. Because cancer gene therapy utilizes true precision medicine. Yes, that's the way!