A study on Cancer by Dr. Manuel Freire-Garabal

Dr. Manuel Freire-Garabal is a professor at the School of Medicine of the University of Santiago de Compostela where he directs a research group focused on the discovery of new anti-tumor drugs. He is an enthusiast of personalized medicine, which he defines as a combination of precision and integrative strategies.

It is precisely this vision that has led the American Society of Clinical Oncology (ASCO) to entitle its 2019 annual conference as “Caring for Every Patient, Learning from Every Patient.”

In simple terms, how can you describe what cancer is?

Cancer is not a single disease; the term defines a number of pathologies that share common characteristics in cells that form a malignant tumor. Cancer cells proliferate without stopping and ignore chemical signals produced by our body to stop dividing or to initiate the programmed cell death process that gets rid of those that are not necessary. Differently, healthy cells divide and grow to replace those that get damaged and then stop.

Surprisingly, cancer cells are also able to use healthy cells for their own benefit, for example, inducing them to form new blood vessels to provide the necessary oxygen and nutrients they need to grow and to favor the elimination of waste products that could kill them. Cancer cells can also hide from the immune system or prevent it from destroying them.

Unlike what happens in benign tumors, malignant cells acquire the ability to infiltrate neighboring tissues and even separate from the primitive tumor to enter the blood stream and lymphatic vessels to reach other distant organs and tissues. It is possible to see cells coming from a primitive breast, colon or prostate cancer growing in the lung, liver on in a bone, where they form metastases.

What are the most recent advances in the treatment of cancer?
It is difficult to summarize in a few words more than 2,400 studies presented in the McCormick Convention Center in Chicago, which has gathered more than 32,000 professionals from around the world at ASCO 2019 celebrated a few days ago.

However, the driving element of this Congress has been “Personalized Medicine”, based largely on the use of drugs against cancer-specific targets and tumor immunotherapy.

As I explained earlier, cancer cells have specific genetic characteristics that are not present in healthy cells. If we identify these biomarkers, we can develop drugs or immune therapies that act selectively against the cancer cells without affecting the healthy ones.

In this way, we will avoid undesirable effects that many of the classic anti-cancer medicines which base their effectiveness in destroying cells that reproduce more quickly. But this not so selective mechanism, since other normal cells of the body also reproduce quickly and continuously, like those from the skin or blood. This lack of selectivity is on the basis of well-known side effects of classic chemotherapy like hair loss, alterations in healing, anemia, immune depression, etc.

Some studies presented in ASCO 2019 reflect the idea that cancers of different origin have common targets or biomarkers that can be used to design similar therapeutic strategies.

This is the case of some types of pancreatic cancer, an aggressive type of malignancy lacks of advanced therapies. A number of these cancers express the same mutation in the BRCA gene that appears in some types of breast and ovarian cancer. Therefore, it can benefit from olaparib, a DNA-repair inhibitor drug in cancer cells that have already proven effective in the latter ones. Clinical assays showed that 22% of patients receiving this drug remained free of disease progression after two years in comparison with 10% for placebo

Encouraging results have also been presented after the use of drugs that act against different therapeutic targets in the same tumor. This is the case of a type of refractory central nervous system tumor harboring gene fusions that affect children and adolescents a that was very difficult to treat but seems to respond to a multi-enzymatic inhibitor drug like entrectinib.

With regard to breast cancer expressing hormonal receptors, , the most common one, the one the association of a first-line endocrine therapy and ribociclib, a target driven drug against a tumor cell enzyme, significantly improves survival rates (from 55 to 71% and 43 to 70% depending on the hormonal the anti-estrogen treatment) in pre-menopausal with advanced disease

Immunotherapy seems to be gaining more and more importance…

The relevance of immunotherapy in Oncology has been demonstrated by its recognition with the 2018 Nobel Prize in Medicine. These techniques try to stimulate the patient’s own immune system that it is responsible for destroying cancer cells. This strategy brings less toxicity and better quality of life to the patient. It is not applied in all types of cancer, nor is effective in all the patients in whom it is applied, but it is being very useful in some types of skin cancer – like melanoma-, kidney, lung, breast, gastric or ear-nose-throat (ENT).

The life expectancy of some patients with advanced lung cancer treated with pembrolizumab, a monoclonal antibody against cancer cells expressing the surface protein PD-L1 has now become years and not months.

Triple-negative breast cancer is less frequent but very aggressive one because it traditionally lacked biomarkers on which to direct innovative treatments. Nevertheless, 50% of the patients with inoperable, locally-advanced triple-negative PD-L1 positive breast cancer who received the antibody atezolizumab were alive after 2 years of treatment versus 37% of controls.

CAR-T therapies that are also revolutionizing blood tumors. This type of immune treatment consists on removing T cells (a type of cell from the immune system) from the patient, modify them at the laboratory, and reintroduce them again in the body to selectively attack cancer cells

Is cancer being cured?

Yes, in many cases. But when it is not possible, the goal is to convert it in chronic disease. In this scenario, therapies should produce fewer side effects and allow the patient to have a better quality of life. Different combinations of therapies are assayed, and artificial intelligence can be useful to design strategies. Researchers have presented studies about AI and cancer on patients over 70 years of age.

Are therefore talking about an integrated dimension of medicine?

Yes, of course. Integrative oncology focuses on the people with the aim to optimize health, to prevent cancer and, when it is diagnosed, to make the patient – and also the social environment – active participant before, during and after cancer treatment to improve outcomes and preserve the quality of life.

What can you tell us about the results of your research group?

My research group is mainly dedicated to the discovery and development of new drugs against cancer. We have obtained new compounds, of synthetic and natural origin that seem to be very effective and can be useful in the future of cancer treatment.

We are developing target-driven compounds that selectively affect the cell division of tumor cells. But also, we are identifying compounds present in natural sources, such as marine microalgae, which are capable of blocking the growth and metastatization of breast and prostate cancers under experimental conditions, is even more effective and safe at this stage than many of those used today in patients.

Unicellular organisms found in the sea, like microalgae, have great potential as a source of future medicines. We are identifying some of these compounds and testing them in different pathologies in cooperation with other international research groups.

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