Amaia Lujambio Goizueta, PhD

Amaia Lujambio Goizueta, PhD, an assistant professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, discusses the unanswered questions currently circulating the hepatocellular carcinoma (HCC) field.

While many studies have been performed in the HCC space, unmet needs still exist and oncologists are left with questions regarding how to treat this disease. Some of these frequently asked questions pertaining to patients with liver cancer include understanding which therapy is best to use for each patient, and how to address heterogeneity which differs among individuals.

Because patients who undergo procedures are at an added risk due to their health, more studies focusing on the genetic makeup of tumors would help to guide researchers in understanding the best ways to treat their patients.

We get new questions every time we get new answers, so it's a never-ending process. But 1 of the biggest questions is which therapy is appropriate for each patient? Even if there are challenges in trying to address that question, there are also advances. There was an interesting study this year where they found out that those patients that have a liver associated with non-alcoholic steatohepatitis, those patients in general respond worse to monotherapy. That was a great discovery this year, but then that begs the question of, what therapy should we use with those patients. Combining research with mouse models and with knowledge from patient samples again will be critical to address this question.

Another interesting question that we are discussing right now is that heterogeneity is different among patients, which is critical, but also a liver tumor within a single patient, they can also be very diverse. Not all the tumor cells within a tumor are identical. That means that you may have some cells that respond to therapy, but others that don't, and the tumor will develop resistance to the therapy. That's going to be another important challenge and a question to address in the next few years. Luckily, now we have technologies based on single-cell analysis of either DNA or mRNA, or proteins that are going to enable us to study this a little bit more.

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Amaia Lujambio Goizueta, PhD, discusses the unanswered questions currently circulating the hepatocellular carcinoma field.

Studies in the Hepatocellular Carcinoma Space Leave Unanswered Questions

Amaia Lujambio Goizueta, PhD, an assistant professor of oncological sciences at the Icahn School of Medicine at Mount Sinai, discusses a new approach to overcoming resistance to immunotherapy for patients with hepatocellular carcinoma (HCC).

Lujambio Goizueta says that overexpression of the Notch receptor proteins may be linked to an oncogene in HCC that prevents cancer from being attacked by the immune system, and also makes the disease resistant to immunotherapy. Researchers are investigating the mechanism of the Notch oncogene in helping tumor cells avoid T cell regulation that would target them. Dysregulation of the Notch pathway is associated with cancer and other conditions.

In patients with HCC that is resistant to immune response, even T cells that reach tumor cells do not attack the cells, she says. Identifying the mechanism of resistance is necessary for immunotherapy to be effective.

According to Lujambio Goizueta, research is currently being done in mouse models to identify the resistance related to Notch signaling. If this research can be transferred to human cells, immunotherapies can be designed to overcome immune escape and induce T cell regulation of tumors.

We have found that tumors that present genetic alteration, which is overexpression of Notch, which can be an oncogene in HCC—they are very good at hiding from the immune system. That makes the tumors with a Notch overexpression be resistant to immunotherapy. I keep coming and repeating the word in immunotherapy because this is one of the therapies that is most promising right now in HCC. So, we are trying to decipher the mechanism by which the Notch oncogene is inducing immune escape.

So, we have found that there are the tumors that have a lower ability to attract T cells, which are cells of the immune system that can recognize specifically the tumor cells and basically kill them. There is a definitely a defect in the ability of those cells to recruit the immune T cells, but also, we are seeing that [even] those T cells that actually managed to get to the tumor, they are not able to kill the tumor cells.

If we are successful with our research, which is conducted mainly in mouse models, and we find a similar mechanism in [patients in] HCC, then that the therapies that we are testing in mice could be used in patients.

Amaia Lujambio Goizueta, PhD, discusses a new approach to overcoming resistance to immunotherapy for patients with hepatocellular carcinoma.

Investigating the Role of the Notch Pathway in HCC Immune Resistance

Amaia Lujambio Goizueta, PhD, an assistant professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai, discusses the challenges and strategies for patients with hepatocellular carcinoma (HCC).

Oncologists make sure to study their patients as much as they can and use strategies such as liquid biopsies which can detect mutations from tumor cells within an individuals blood. Basic and translational research also can help oncologists come up with the best therapy options for each genetic alteration as these implementations are key to providing patients with the best treatments.

Still, more research is needed in the liver cancer field, especially due to the fact that patients who undergo procedures are at an added risk because of their health. Studies focusing on the genetic makeup of individualized tumors would help researchers further understand how to test patients with HCC.

Ideally, we would like to study the genetic makeup of the tumors of every patient and how they respond to each therapy that patient is receiving, so that we have a more complete picture. This is all very challenging because of this fact.

There are other strategies that people are developing such as liquid biopsies, which basically means that you can detect the mutations from the tumor cells in the blood of the patient. It is much safer and less traumatic than getting a biopsy and it may offer a similar level of information in terms of choosing the best therapy. Whenever possible, we need to study as much as we can, every single aspect of the tumors. If that's not possible, then implementing liquid biopsies could be a great strategy as well. Then we need to combine basic and translational research, so that we come up with the best therapy options for each genetic alteration or each mutation.

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Amaia Lujambio Goizueta, PhD, discusses the challenges and strategies for patients with hepatocellular carcinoma (HCC).

Amaia Lujambio Goizueta, PhD | Authors

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Studies in the Hepatocellular Carcinoma Space Leave Unanswered Questions

Investigating the Role of the Notch Pathway in HCC Immune Resistance

More Research Needed for Patients With Liver Tumors