What has happened in the past 20 years of fighting cancer

For the international day against cancer, we remind Airc what progress has been made in research, from the human genome to immunotherapy

February 4 is the International Cancer Day and this year marks the twentieth anniversary. It was in fact established in 2000 in Paris, on the occasion of the World Summit Against Cancer for the New Millennium . Like every year, Airc Foundation participates in the campaign, and has decided to remember what happened in these 20 years. Here the information for donations.

Because if it is true that the search for the cure (indeed, of the cures) does not stop, the progress has been made . Anyone who has been close to a patient who has lost his life can certainly say that they have not been enough. Especially if we consider that in the media, often and willingly, preliminary and incomplete (if not fraudulent) results are exalted which feed unjustified hopes. But taking a look at the progress actually achieved only in the last twenty years there is reason to continue to trust scientific research: cancer becomes increasingly treatable .

2000 – 2005: the genetic revolution begins

The first draft of the human genome was completed in the same year that this day was established. Someone could say that it was destiny: it was probably genetics, more than any other discipline, that dragged the research against tumors. The following year the imatinib , the first anti-tumor drug to target

would be approved

molecular developed with a rational approach. It means that the drug, effective against chronic myeloid leukemia , was designed starting from the molecular mechanism that caused the disease. In chronic myeloid leukemia, a chromosomal alteration leads to a mutated gene , from which derives an abnormal protein capable of producing the tumor. The drug binds to this protein, inhibiting its action. Thanks to this type of therapy, today it survives until 95% of patients.

The draft of the genome was published simultaneously in the most popular scientific journals in the world: Nature and Science

The principle is similar to that of anti-angiogenic drugs (which block the formation of blood vessels, starving the tumor) and anti-EGFR (block the receptor, on the cell surface, by the growth factor of the epidermis). Approved in 2004, in both cases custom molecules are used, such as monoclonal antibodies, to block the action of specific proteins that help the tumor. A step forward is also made in surgery . In 2002 a study by Umberto Veronesi proves that the quadrantectomy , where only a part of the breast affected by cancer is removed, is as effective as mastectomy, with total removal.

Progress is also made with prevention. Despite the denial pressures, in 2005 the ban on smoking in public places becomes a reality. It is indeed increasingly clear from studies that many cancers could be avoided by adjusting diet and other behaviors. The Airc also recalls the Nobel prize for the discovery that the bacterium Helicobacter pylori can cause, in addition to the ulcer, also the stomach cancer . Of the 2005 also the first nanopharmaceutical , consisting of a small biological envelope, called a liposome, used to transport a chemotherapy drug (doxorubicin) directly to cancer.

2006 – 2010: vaccines and Nobel Prize

In this luster is approved, in 2006, the vaccine against papilloma virus , the virus that causes cervical cancer. The vaccine allows not only to prevent this cancer, but also others caused in part by the virus itself (anus, vagina, penis, oropharynx). In 2008 the discovery of the causal link and between the virus and the disease is awarded the Nobel prize . In 2010 it is approved, in the United States , another vaccine : sipuleucel-T . In reality in this case it is a therapeutic vaccine , not preventive. It should train the immune system to attack prostate cancer . Survival is low, and has not been approved in Europe, but later the same rationale will be used successfully in other cancers.

In 2007 trabectedin , a new anticancer drug developed in Italy by Maurizio d'Incalci and collaborators, used in the treatment of sarcomas is approved. It also continues to deepen the role of diet and exercise in prevention, but also aspirin seems to have a protective effect for colorectal cancer, according to a study of the 2010. Diagnostics also make progress thanks to genetics, for example for breast cancer a rapid test called GeneSearch BLN Assay is born which allows, during the same surgery, to know if the lymph nodes have been infiltrated by metastases, and must therefore be removed, or not.

Another Nobel , in 2009, goes to the discovery that the telomeres , structures at the end of the chromosomes that regulate cell life: duplication after duplication shortens until the cell dies. Cancer cells, on the other hand, are immortal because an enzyme, telomerase, is kept active, which keeps the length intact.

2011 – 2015: immunotherapy arrives

The first attempt to use the immune system against cancer is from the 19th century . The Dr. William B. Coley healed a patient by deliberately infecting him with a bacterium: he injected streptococcus directly into the tumor. The following immune reaction got rid of streptococcus and also of the tumor. The advent of the first chemotherapists made forget the Coley experiment , but in the last decade scientists have recovered. In 2011 it was approved by the FDA for melanoma the drug ipilimumab , a monoclonal antibody that binds to the cells of the immune system preventing their inhibition by the tumor. In other words, cancerous cells, previously immune, become attackable . immunotherapy , together with surgery, radiotherapy and chemotherapy, will soon be considered the fourth weapon against cancer .

The following year Crispr makes genomic editing within everyone's reach , opening up new possibilities also for cancer therapies. In this period there are also two major media cases, which make it clear how complicated it is to communicate some issues. Angelina Jolie in 2013 makes public her choice of undergo a double preventive mastectomy, as it carries genes that greatly increased the risk of developing breast cancer. In the 2015 instead there is the case of the Iarc ( International Agency for Research on Cancer) which classifies red meat as probably carcinogenic , and carcinogenic sausages. The debate that followed has not yet ended, but advice on cancer and diet always apply.

Another important Italian discovery: Dr. Lucia del Mastro shows that triptorelin maintains the fertility of women undergoing chemotherapy.

2015 – today: Car-t cells and Big data

Over the past five years Car-t has become a family name. Together with immunotherapy, awarded in 2018 with the Nobel Prize in Medicine, it is among the most commented advanced therapies. Wired has often dealt with this procedure, in which the patient's lymphocytes are taken, genetically modified in the laboratory to attack the cancer cells, multiplied and then reinfused in the patient. Since last year tisagenlecleucel , a Car-t therapy for acute lymphoblastic leukemia and diffuse large B-cell lymphoma, it is also available and refundable in Italy. They are extremely expensive therapies, and efficacy varies according to the type of cancer, but complete remission from the tumor can also be obtained. There are no such therapies for solid tumors yet, but they are under study.

(infographic: Malaghan Institute / Aifa)

Knowledge of cancer as a complex biological entity has meanwhile continued to increase. Thanks to an Italian team we know that pancreatic cancer has four subtypes, essential information for therapies that are increasingly tailored . From a regulatory point of view, Airc underlines the approval agnostic in the 2017 of pembrolizumab , a monoclonal antibody. Agnostica means that it does not matter where the cancer develops, but the presence of a specific molecular marker . It means that the same drug can be used for many cancers , in adult and pediatric patients. In 2018 and 2019 two other drugs have been approved by the FDA in this way: larotrectinib and entrectinib.

Big data have also been applied to the study of cancer. For example, last year the Cancer Dependency Map project used Crispr to deactivate over 20000 genes in 300 cancer models, of 30 different types. In this way they managed to identify 600 among the most promising targets for future precision therapies, that is, the genes that seem indispensable for the survival of the tumor. In this way it is hoped to accelerate the discovery of new drugs .

A year earlier, however, the genetic Atlas of tumors was born. 11000 tumors, gods 33 more types widespread, they have been studied to understand how and where they are born, thanks to the homic disciplines . The 27 research produced by this project has been possible thanks to years of collaboration between several American research institutes, including the National Human Genome Research Institute which, together with Craig Venter, sequenced our genome twenty years ago.

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