Why New Targeted Drugs Are Unlikely To Solve The Problem Of Cancer?

The possibility of getting cancer sends shivers down most people’s back. This afflictive ailment can knock on the door of individuals of all ages and is responsible for the death of millions every single year. Management options for cancer are diverse, but most of them are well recognized for their serious adverse events. This happens because anti-cancer substances (collectively known as chemotherapeutic agents) act on cells that have a singular trait: they divide rapidly. Unfortunately, this trait is not exclusive of cancerous cells. Healthy cells, such as cells in the digestive tract, blood and hair follicles, also have this property. Therefore, the usefulness of chemotherapy is limited due to its toxicity and, in some cases, its limited efficacy.

Targeted anti-cancer therapy – new approach to treat cancer

The development of therapeutic approaches that avoid chemotherapy’s terrible side effects and maximize the probability of cure is an ongoing effort. Current cancer research is now focusing on a very specific approach to treatment: targeted drug therapy. Today’s technologies and knowledge have allowed researchers to get a clear view of the genetic mutations and other modifications that underlie cancerous diseases. It is thought that by creating molecules that go after these specific modifications, new drugs that attack cancer cells and do less damage to normal cells can be developed. Some examples of targeted therapies already available on the market include gefitinib to treat non-small cell lung cancer and bortezomib to treat multiple myeloma that does not respond to other treatments.

However promising these drugs might be, they should not be regarded as an infallible solution. They are still far from being the indisputable cure for cancer. But if they’re targeted and highly specific, why is it that they are not as good as we thought them to be?

Cancer cells constantly change in the course of tumor growth

Cancerous growths usually begin as single cell, which suffers various mutations and ends up starting dividing uncontrollably. If that were to be the only mutation, targeted therapies would have no reason to fail. But cancerous cells mutate almost continuously in the course of disease progression, and these consecutive mutations make them more and more aggressive and drug resistant.

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At best, targeted therapies attack one group of mutated cells. While this might help slow down the progression of the disease, it does not put an end to it – precisely because it leaves many subgroups of cancerous cells undamaged. Many researchers have looked into this problem and there is plenty of evidence supporting its veracity.

New Mutations In The Cells Of Tumor Are The Biggest Tumbling Block For Anti-cancer Therapy

A recent study, published in the beginning of this year, analyzed the genetic heterogeneity (variations) of multiple myelomas, the second most common type of hematological cancer. The study revealed that this sort of cancer is deeply affected by significant genetic events, thus rendering genetic variability among the cancerous cells a normal situation in patients with this condition. The final conclusion? Genetic diversity in multiple myeloma is a strong obstacle to the effectiveness of targeted therapy and a study of the heterogeneity of this category of cancer is of high importance for future treatment guidance.

The problem of so-called subclonal populations, presence of cells with different genetic make-ups, is not unique to multiple myeloma. Practically all types of cancer have this feature. Researchers are now studying the other forms of cancer to look for populations of genetically diverse cells within a single tumor. This knowledge will help to select the most appropriate targeted therapy.

The fact that cancer changes during disease progression is known for almost 30 years

The acknowledgement of genetic diversity within tumors as a promoter of carcinogenesis is not exactly new. Back in 1984, a study was published addressing the issue of the generation of diversity within a tumor and how that was related to the best therapeutic options available at that time.

This can be explained by plain randomness or by more complex mechanisms of therapeutic resistance. It was concluded that the heterogeneous nature of malignant cells that composed the same cancer with respect to radiation sensitivity, susceptibility to cytotoxic or cytostatic drugs or hyperthermia could pose a problem during and after cancer treatment is terminated. This means the disease can come back after being eliminated almost completely.  A while later, in 1997, an analysis of the genomic alterations behind the human breast cancer was conducted. This examples show that understanding of mutations causing cancer and its importance in outlining the treatment strategy was a well-regarded problem way before the launch of the first targeted therapies.

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Targeted therapy can only be given to patients with specific genetic alterations

The problem of genetic and phenotypic diversity within tumors is a transversal problem, i.e., it affects all sorts of cancer: lung cancer, colorectal cancer, melanoma, and so on. Targeted therapies do not stand against this powerful mechanism of differentiation that all cancer cells appear to have. As such, they should not be regarded as a “cure” and a “fit for all”. Targeted therapies may be very useful and even induce remission in some patients whose cancers have very specific properties. Consulting with an experienced oncologist is key in identifying the best therapeutic approach to each patient’s own tumor – for some surgery is enough, for others chemotherapy does the job. For others, targeted therapy or various treatment combinations might be advised. Meanwhile, research into the cancer’s intricate inner working continues and the hope for a better understanding of said mechanisms stands.