Liver cancer treatment – what is next?

Modern methodology

The modern drug design approach for anti-cancer products seems to be based on a concept that a disease can be cured if:

  1. The pathological mechanism that causes the disease (i.e something that can be the drug target, usually proteins) is identified
  2. An active chemical substance can inhibit this very mechanism/protein.

 

More details about this here: https://www.youtube.com/watch?v=3GvmOfj-Puk

 

This is by no doubt a very simple and straightforward approach. It does not differ very much from antibiotics development, where the pathogen is most often the obvious target. To treat this kind of disease is therefore a matter of finding a chemical that directly or indirectly kills the bug. However, this might not be the only and probably also not the best approach in cancer of other non-infectious and complex conditions.

 

The creativity in drug development has now narrowed into providing screening processes automatization and methods to identify the target. The success of some few drug candidates and validated targets obtained using this strategy is now being endlessly copied by many “me-too” products in a hope that just “my me-too” product will be better than the original.

Drug

Company

Mode of action

Type

Phase

1. Afinitor

Novartis

mTOR inhibitor

oral

Phase III

2. Brivanib

Bristol-Myers Squibb

VEGFR, FGFR inhibitor

oral

Phase III

3. Linifanib

Abbott

VEGFR, FGFR, FLT3 inhibitor

oral

Phase III

4. Muparfostat

Medigen Biotech

Heparanase, VEGF, FGF inhibitor

injectable

Phase III

5. Orantinib

Taino

VEGFR-2, FGFR-2, PDGFR inhibitor

oral

Phase III

6. Peretinoin

Kowa

TGF-alpha

oral

Phase III

7. Sutent

Pfizer

VEGFR, PDGFR, FLT3, c-kit, RET inhibitor

oral

Phase III

8. Tivantinib

ArQule

c-MET

oral

Phase III

9. TS-1

Taino

Thymidylate synthase inhibitor

oral

Phase III

 

Is it good or bad?

Liver cancer is a cancer with the growing mortality and lack of satisfactory treatment for the majority of patients. The needs are, in other words, still largely unmet. From the business point of view it should be an extremely favorable market both today and in the future for pharma companies to bet on, to be present in, to thrive in. And indeed, it looks like that the interest is high – a lot of products went into the developmental pipeline during the past decade… Until they fail one after one or their development is being discontinued (failed). Why so?

 

Let’s take a closer look into 9 latest products against liver cancer discontinued after phase III of the clinical development, i.e. after the most expensive phase. The modes of action of these compounds were known to be successful in other cancer types, and yet these drugs have failed. Does it mean that liver cancer needs a different strategy? What if all modern methodology of drug design is doomed to failure just in liver cancer due to some special features of this organ?

 

Special treatment

It looks like “one target – one molecule” methodology that is so popular and successful in other cancer types does not work equally well for development of efficient liver cancer products. Tens of target proteins were examined and millions of compounds were tested as potential drug candidates against liver cancer, and failed one after one. Which is why the odds are now very low that another new synthesized chemical compound will magically be very efficient. It looks like liver cancer needs a very special treatment.

But the market is still huge, needs are unmet and conditions for (big or small) pharma are favorable more than ever.

And lucky will be those who can first propose a solution for a more efficient treatment of liver cancer. In baseball it is called the “home run,” and in drug development it will hopefully be called the “BeloGal® track”.

 

Igor.

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