How to beat cancer: five scientifically based reasons for optimism

In 2018, 9,6 a million people in the world died from cancer. Cancer is the cause of about one in six deaths in the world, according to the World Health Organization (WHO). Research centers, pharmaceutical companies and governments are investing billions of dollars in the search for new methods of treatment, and each year they are moving toward a goal: to learn how to prevent and heal cancer.

Фото: Depositphotos

Ко World Cancer Daywhich is celebrated on February 4, Present Tense chose important scientific advances of the past year, which help in the fight against cancer - based on annual report The American Society of Clinical Oncology (AOAC), the resulting annual review in the journal “Oncology” and other sources.

Reaching the year in the USA: treating rare forms of cancer

The American Society of Clinical Oncology called the achievement of the year success in treating rare forms of cancer. In the USA, this is approximately one in five of the detected cases, and, as a rule, progress in treating these diseases has not kept pace with the development of therapy for more common cancers. For clinical studies of rare forms of cancer, it is much more difficult to find the right number of participants, and therefore to test new treatments. Nevertheless, the past year was marked by several successes in this area.

In 2018, the first treatment in 50 years for a rare form of thyroid cancer, anaplastic carcinoma with the BRAF V600E mutation, was found. The tumor, which responded poorly to standard treatment methods, nevertheless turned out to be sensitive to targeted therapy with the drugs Dabrafenib (commercial name Tafinlar) and Trametinib (Mekinist) - 61% patients in clinical trial the tumor partially decreased in size or completely disappeared.

The first remedy for improving survival without signs of progression in desmoid fibroma, a rare form of sarcoma, and a malignant tumor, sorafenib (Nexavar), has also appeared. A positive reaction was recorded in 87% of patients from the group who received this medicine.

Rare earth lutetium, or rather its radioactive isotope (177Lu) in the new drug “177Lu-dotatate” (Lutathera) successfully fights gastroenteropancreatic neuroendocrine tumors (Apple creator Steve Jobs died from this) in the later stages: the risk of developing the disease or death in patients who received the drug was reduced by 79%. The medicine uses a combination of special peptides, analogues of the hormone somatostatin, with a radioactive isotope. The peptide finds cancer cells that are destroyed by radiation.

Such treatment is called targeted radio receptor therapy, and it has been offered in the EU and Israel for several years. Interested the creation of domestic analogues of similar therapy and the Russian Ministry of Health.

Scientists also found a way to extend the life of patients with serous carcinoma of the uterus, in whom excessive production — expression — of the HER2 protein was found (approximately 30% of cases). To do this, to their standard chemotherapy was added trastuzumab, which made it possible to increase the duration of survival without progression by almost half.

In 2018, American scientists also found the first effective ways to combat tenosynovial giant cell tumors, a rare form of joint cancer that usually affects young people. In 39% of cases, the tumor response to treatment with pexidartinib was recorded.

Determine cancer by blood test

Early detection of cancer usually determines the success of further treatment. But it is in the early stages that it is difficult to find cancer. The emergence of cheap, simple and universal ways of detecting cancer could turn the whole industry.

Recent studies have shown that a blood test that studies multiple markers — both genes and proteins — can be a fairly accurate way to determine cancer.

One of the promising options CancerSEEK, allows you to identify up to eight common cancers based on biomarkers and individual gene mutations characteristic for them. The tests showed that the CancerSEEK technique revealed signs of cancer with 69-98% sensitivity (i.e. the probability that a positive result actually indicates cancer) and 99% specificity (i.e. the probability that a negative result really means no cancer).

Australian scientists were able to determine universal DNA trait immediately for several types of cancer (breast, prostate, intestines), which can then be used to conduct quick and simple tests.

Statements on the topic of revolutionary universal methods of cancer detection by blood analysis done before, but the case has not yet reached the existing and clinically confirmed results.

Immunotherapy: breakthrough direction

In 2018, the Nobel Prize in Medicine got two scientists who studied the mechanisms of immune response checkpoints: special receptors and molecules with the help of which the body - and, as it turns out, many tumors - suppresses the excessive activity of T-lymphocytes, the “killer cells” of the immune system, so that did not destroy normal cells (and tumor cells masquerading as them).

Later scientists have understoodthat if these blocking “checkpoint” mechanisms are blocked, then T-lymphocytes begin to actively fight cancer cells. More than 15 years after this important discovery, immunotherapy—that is, using one’s own immunity to fight cancer—is becoming an increasingly promising treatment for cancer, and drugs (called “checkpoint inhibitors”) are becoming more and more available.

Activation of T-lymphocytes does not affect all tumors yet, its effectiveness depends on the genotype of each patient. Moreover, such treatment is expensive and is not used everywhere.

The American Society of Clinical Oncology notes that the past year has brought not only new immunotherapy drugs, but also several confirmations of the effectiveness of immunotherapy at the early stages of treatment and in combination with other methods of cancer therapy.

So, inhibitors of checkpoint atezolizumab (Tecentriq) and pembrolizumab (Keytruda) showed effectiveness as a means of first-line treatment against non-small cell lung cancer in the later stages. Renal cell carcinoma with an unfavorable prognosis responded well to treatment with nivolumab (OPDIVO) and ipilimumab (Yervoy), checkpoint inhibitors, commonly used to treat melanoma.

By the way, the combination of these drugs in patients with melanoma, metastasizing to the brain, showed the disappearance of the tumor in a quarter of cases (26%) and its decrease by almost a third (30%). At the same time, 82% of patients who received these drugs remained alive after a year from the start of treatment, whereas earlier they could count a maximum for weeks or months.

The disadvantages of such “cocktails” are serious side effects. They were noted in 55% of clinical trial participants with metastatic melanoma.

But immunotherapy involves not only checkpoint inhibitors. In 2017, the US FDA regulator (Food and Drug Administration) approved the revolutionary immunotherapy method: gene CAR-T. Officially, this method is called “adoptive immunotherapy with genetically modified T lymphocytes expressing chimeric antigen receptors”.

The medicine, called Tisagenlecleucel-T (Kymriah), is prepared separately for each patient with a particular form of acute lymphoblastic leukemia. T cells of the immune system are taken from a person, modified to effectively “attack” cancer cells (using the biomarker CD19) and reintroduced.

The therapy was extremely successful and very expensive - about half a million dollars per course. A little later, another similar medicine, Yescarta, Was approved for another type of cancer, aggressive B-cell lymphoma in adults (the most common form of non-Hodgkin's lymphoma) - if the tumor does not respond to another therapy. Later, Kymriah was approved for the treatment of this cancer.

Clinical trials show long periods of survival (complete remission for half of the participants in the Yescarta test) and confirm the effectiveness of this therapy. The main disadvantages, in addition to cost, are serious side effects, including high fever, difficulty breathing, severe nausea or diarrhea. Another problem is the complexity in the production of medicines, which is why sales of Kymriah were far below expected.

Microbes and cancer: a promising direction

The human body is home to a huge variety of microorganisms, and it is even sometimes referred to as a “superorganism” made up of human cells and microbes. Laboratory and clinical studies show that changes in individual microbiome organisms (the “ecosystem” of all human microorganisms) can lead to the development of diseases, including cancer.

And although individual microbes can accelerate the growth of tumors, others seem to help a person’s immune mechanisms more effectively deal with them. Researchers are paying more attention to this area.

In two large studies, scientists found that, for example, an abundance of corynebacteria (Corynebacterium) and Kingella in the oral cavity indicated less dangerous forms of head and neck squamous cell carcinoma, while for example the presence of tannerella (Tannerella forsythia) was associated with more dangerous forms of cancer esophagus - esophageal adenocarcinoma. Scientists are only exploring the possibility of using this knowledge to prevent or treat certain head and neck cancers, but they note that further analysis of the microbiome of each patient may be necessary in the treatment of cancer.

Targeted therapy: new drugs

In the 2018 year, new types of targeted cancer therapy were actively developing. This method of treating cancer, unlike chemotherapy, does not hit all the cells at once, but acts selectively, only on tumor cells marked with “targets” - certain genetic mutations. Targeted therapy has been developing for over a decade; last year, new promising drugs appeared.

For example, FDA approved osimetinib (Tagrisso) for the treatment of lung cancer with an EGFR mutation - a drug almost doubles the survival time without signs of disease. There are new ways to treat certain types of advanced breast cancer (Abemacyclib, Verzenio) and acute myeloid leukemia in the elderly (venetoclax, venclexta).

New Goals for Researchers: Nine Directions

The American Society of Clinical Oncology has named nine areas in which scientists should focus their work. According to the AACO version, they should:

1. Find ways to better predict the response of cancer to immunotherapy,
2. To learn to better identify patients who really need postoperative (adjuvant) therapy,
3. Transfer the achievements of cancer cell therapy to solid tumors,
4. Strengthen research on targeted therapies for the treatment of children with cancer,
5. Optimize the treatment of older people with cancer,
6. Increase equitable access to clinical cancer research,
7. Reduce the long-term effects of cancer treatment
8. It is better to investigate the effects of obesity on cancer occurrence and its treatment,
9. Create strategies for the detection and treatment of precancerous conditions.

“These priorities are consistent with our vision to find the next generation of cancer cures and reduce the negative impact cancer has on patients' lives,” said Richard L. Schilsky, senior vice president of AOCO. “These priorities are intended to highlight the areas where progress is most needed and where it will be most promising.”

Фото: Depositphotos

Reasons for pessimism

Many scientific advances and new methods of treatment so far only slightly improve the prognosis and are not always able to lead to a complete or even prolonged deliverance from tumors and metastases. It seems that in the short term such achievements are not foreseen, especially if one does not pay attention to loud statements without sufficient scientific and clinical evidence.

Another problem: modern drugs for the complex therapy of cancer are very expensive - from tens to hundreds of thousands of dollars - and are far from being available everywhere. Not everywhere can take part in the trials of new experimental anti-cancer drugs and treatment regimens.

In this case, according to who, almost 70% of all cancer deaths occur in low- and middle-income countries, where there is a shortage of opportunities not only for treatment, but also for the diagnosis of cancer.

“A new miracle cure for cancer”

In addition to serious scientific research in peer-reviewed journals and clinical trial results, every year there are stories of a “magic” new cancer drug or treatment that is about to revolutionize oncology.

This announcement has already happened in 2019: Israeli startup Accelerated Evolution Biotechnologies Ltd. (AEBI) He pledged the world will be “completely cured of cancer” within the next year.

In an interview with The Jerusalem Post CEO Dan Aridor (Dan Aridor) said that their anti-cancer therapy “MuTaTo” (multi-target toxin, “multi-purpose toxin”) - based on a combination of several peptides and peptide-toxin for cancer cells - will be effective from the first day, the course treatment will take only a few weeks and it will be beneficial to differ from competitors not only by the absence of side effects, but also by price. The authors are talking about successful studies in mice and are about to begin clinical trials soon, which they say will take several years.

“Unfortunately, according to the experience of other similarly loud announcements of breakthrough technologies for the treatment of cancer, most likely [the current announcement] will also not be successful, - считает deputy director of the American Cancer Society Leonard Lichtenfield. - We all hope that a cure for cancer will be found and will be found quickly. It is certainly possible that this approach [of Israeli scholars] might work. But experience has shown us many times that between successful experiments on mice and the effective, beneficial use of laboratory discoveries for treating real patients lies a long and difficult road, full of unforeseen and unexpected obstacles. ”

The Head of the Cancer Center at NYU Langone Health Hospital, Dr. Benjamin Niil, spoke out more rigidly: “I really think it is very unfair and almost cruel to give such – most likely false – hopes to cancer patients.”

be healthy

While the perfect cure for all forms of cancer is not invented, try to reduce the risk of cancer by changing your lifestyle. WHO experts believe that this can be prevented from 30 to 50% of cancers.

Quit Smoking: Tobacco Use Who calls the most important risk factor. Every fifth death from cancer is associated with smoking.

Scientists attribute about a third of all cancer deaths to obesity, inadequate consumption of fruits and vegetables, alcohol and tobacco use, and lack of physical activity.

WHO recommends doing vaccinations against infections caused by the human papillomavirus (HPV) and the hepatitis B virus, are less affected by ultraviolet radiation (for example, sunbathing), monitor workplace safety and reduce the effects of ionizing radiation.

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