Sunday, November 17, 2024

Path to precision: Targeted cancer drugs go from table to trials to bedside

Very recommendable, but also a very long overview and history article! Cancer is history (soon)!

Hopefully, machine learning & AI will accelerated the development of effective new treatments of cancer!

"[Janet] Rowley had the first evidence that genetic abnormalities were the cause of cancer. She published her findings in 1973, with the CML translocation published in a single-author study in Nature. In the years that followed, she strongly advocated for the idea that the abnormalities were significant for cancer. But she was initially met with skepticism. At the time, many researchers considered chromosomal abnormalities to be a result of cancer, not the other way around. ...

By the mid-1990s, researchers had developed a drug that blocks the BCR-ABL protein, a tyrosine kinase inhibitor (TKI) called imatinib. For patients in the chronic phase of CML—about 90 percent of CML patients—imatinib raised the 10-year survival rate from less than 50 percent to a little over 80 percent. Imatinib (sold as Gleevec or Glivec) earned approval from the Food and Drug Administration in 2001, marking the first approval for a cancer therapy targeting a known genetic alteration. ...

The development of gene-targeting cancer therapies skyrocketed. Classes of TKIs, like imatinib, expanded particularly fast. There are now over 50 FDA-approved TKIs targeting a wide variety of cancers. For instance, the TKIs lapatinib, neratinib, tucatinib, and pyrotinib target human epidermal growth factor receptor 2 (HER2), which runs amok in some breast and gastric cancers. The TKI ruxolitinib targets Janus kinase 2, which is often mutated in the rare blood cancer myelofibrosis and the slow-growing blood cancer polycythemia vera. CML patients, meanwhile, now have five TKI therapies to choose from. ..."

Path to precision: Targeted cancer drugs go from table to trials to bedside - Ars Technica "What started in a scientist's dining room is now in tissue-agnostic combo trials."


Schematic of the 9;22 translocation and the creation of the BCR::ABL fusion gene.


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