New Drugs for Cancer

The long development process of lab screening and animal tests is expensive and weeds out most compounds.  Only about 0.1% of potential medicines eventually make it to clinical trials in human subjects.

The reasons medicines are screened out are many.  Some work to kill malignant cells but are not specific enough for the targets the scientists set for them or are poisonous.  Others are unstable and would break down in any serious clinical use.  Others may work at the cellular level but there is no way to get the medicine to the cells through administration to the body (e.g. oral, IV).

Once medicines make it to clinical trials, most of those are screened out too.  For one reason or another the backers drop development and do not seek to advance the medicine to the next phase.  Reasons include overly severe side effects or too many side effects or ineffectiveness of the medicine.

Future of Chemotherapy

The  drug discovery industry today divides potential new therapeutic compounds into two categories: small molecule and biologics.  Remember when you were in chemistry class and you drew out the structure of molecules?  Any molecule you can draw on a piece of paper is a “small molecule”.  Most medicine are small molecule drugs.  They are often made by chemical synthesis or some are made by fermentation.

Biologics, also called biopharmaceuticals, are enormous molecules.  If you know anything about proteins you know they can have thousands of atoms in a molecule.  Biologics are often, but not always proteins.  They are often referred to as biotech drugs.  They are produced by living cells.  As therapeutics biologics first appeared in oncology medicine in the 1990s.  Under the categories immunotherapy and monoclonal antibodies, they offer greater specificity and fewer side effects.

A larger share of new oncology drugs are biologic than drugs for other diseases.  Going forward, industry observers anticipate new combinations of existing therapeutic products and new solutions such as cancer vaccines, nucleic-acid therapies, and new antibodies.

New Immunotherapy

In recent years, development of new immunotherapy agents has revolutionized cancer treatment. These drugs induce or potentiate the anti-tumor activity of the immune system.

The immune system identifies tumors and triggers an anti-tumor response. Such response, however, is modulated by stimulatory and inhibitory factors. The new immunomodulating agents are based on inhibition of immune system inhibitors and on enhancement of stimulatory factors. The novelty of this approach stems from the fact that the drug targets the host immune cells and not the tumor itself.  Antibody-drug conjugates are related avenue of research that is yielding promising results.  Following significant therapeutic and commercial successes, a lot of efforts are being put in the development of new ADCs. With milder side effects, ADCs promise to substantially expand the medical oncologist’s toolkit for fighting cancer.

More on immnotherapy.

Notch Inhibitors

It is known that some genes cause or contribute to the initiation and/or growth of cancer, and one are of research is whether blocking the action of those genes can stop or prevent the cancer. The Notch gene was first found in 1917 and now it turns out that the gene is implicated in a signaling system that is part of tumor growth.

Cell membrane surfaces have receptors now referred to as Notch receptors. In scientific literature there are referred to as Notch1 (or more formally Notch homolog 1 translocation-associated receptos), Notch2, Notch3, and Notch4.

A bunch of potential notch inhibitors are being investigated for their effects on cancer proliferation. There is an interest in combining them with hedgehog inhibitors. Cancer stem cells – aka tumor-initiating cells – are an area in which scientists think notch inhibitors might be helpful. There are no notch inhibitor therapies in clinical use at this time.

Consequences of Disrupted Notch Signaling in Bladder Cancer.

Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer.

NOTCH pathway inactivation promotes bladder cancer progression.

NOTCH Decoys That Selectively Block DLL/NOTCH or JAG/NOTCH Disrupt Angiogenesis by Unique Mechanisms to Inhibit Tumor Growth
.

Changes in the regulation of the Notch signaling pathway are temporally correlated with regenerative failure in the mouse cochlea
.

Notch inhibitors for pulmonary arterial hypertension – SciBX Science Business Exchange

Notch inhibition reverses kidney failure – Nature

PARP Inhibitors

PARP Inhibitors (PARPi) are a promising group of drugs with a wide potential as sensitizers for chemotherapy and radiotherapy. However, more research is needed in order to demonstrate their complete potential.

A Shortage of Test Patients

There is so much interest from pharmaceutical companies in developing new immunotherapy treatments and personalized therapy that experts worry there aren’t enough cancer patients to fill up the openings in clinical trials needed to test the new therapies.