How does cancer's resistance overwhelm targeted therapy?

Oncogenic kinase inhibitors, once hailed as miracle drugs, represent a $42B annual market. After a period of “miraculous results”, many kinase inhibitors are being overwhelmed by cancer’s resistance. The DNA SEQ Alliance was formed to address that problem.

What are kinases?

A kinase is an enzyme that attaches a phosphate group to a protein. Kinases serve as mobile transfer stations in a sprawling network of intracellular communications. Many of the messages they transmit tell the cell when to grow and divide. Some kinases initiate the signals; others act as receptors, receiving the messages and forwarding them. What transpires between the enzymes is an elaborate relay race, with each protein passing a “baton” of information to the next molecule in the chain.

The communication comes through a process called phosphorylation: one kinase transfers a phosphate group -a compact ring of oxygen surrounding an atom of phosphorus - to a second molecule, giving the latter a jolt of chemical energy, and setting it into motion.

Kinases can be viewed as the universal ON/OFF switches that regulate numerous functions.

The critical role of kinases in cancer cannot be overstated. Kinases participate in diverse cellular pathways and their misregulation leads to many human cancers. In particular, mutant kinases drive the behavior of malignant cells in many cancers. Mutant kinases that drive malignancy are the focus of a concerted worldwide effort to specifically target and inhibit them. This effort of the pharmaceutical industry addresses the $42 billion annual market of the kinase-based therapeutic portfolio for cancer. The mechanism of resistance that develops to overcome currently available inhibitors is the focus of DNA SEQ’s scientific work and patented discoveries.

Today there are over 35 FDA approved kinase-targeted therapies, yet many of the patients on these, initially effective therapies, will be overwhelmed by cancer’s resistance to these very same drugs.
The MISSION of the DNA SEQ Alliance is to discover how the resistance overwhelms these drugs, how to better fight the resistance, and how to develop therapies that will overcome the resistance.