Author: George Weiner
Date: 2016-12-07 11:43:34

I just returned from one of my favorite meetings of the year, the annual American Society of Hematology (ASH) meeting that I have attended almost every year since becoming a cancer researcher  in the late 1980s. At the ASH annual meeting, research and clinical advances in blood cancers and other blood disorders are presented and discussed by scientists and physicians. Several presentations at this year’s meeting led me to think about my first ASH meetings.

Back in those days, researchers and physicians (myself included) were excited about scientific discoveries that suggested very novel treatment approaches for blood diseases.  These included…

• Activating the patient’s immune system to kill blood cancer cells by using cancer vaccines.
• Retargeting cells of the immune system to kill blood cancer cells.
• Delivering cancer killing drugs directly to the blood cancer cells through the use of antibodies to enhance the anti-cancer effects of the drugs while sparing other normal cells, thereby limiting side effects.
• Using gene therapy to correct inherited disorders such as the defect in blood clotting that is responsible for hemophilia.

While there was clear scientific rationale behind these approaches, and great enthusiasm for applying them to clinical medicine, our knowledge and our tools were limited compared to those of today. Each of these concepts was explored in the laboratory and eventually in clinical trials. We learned steadily from this effort, but there was frustratingly little to show in applying these ideas to the care of our patients. Indeed, at some point over the past couple of decades, each of these novel concepts was felt to be “a failed hypothesis”. Funding from the government and the private sector to pursue these ideas dwindled. Hopes of researchers, physicians, and most importantly patients, were dashed.

Fortunately, there were persistent researchers, physicians, and patient advocates – true believers - who continued to pursue each of these approaches despite naysayers and limited funding. Such persistent researchers often presented their findings to nearly empty rooms at subsequent ASH meetings or stood alone by their ASH posters as others attending the conference walked by to look at more “cutting edge” posters (or to get to the table with the pretzels). Researchers who kept working on these concepts felt like they had been exiled to the scientific wilderness.

For me, ASH 2016 was notable for the number of such “failed hypotheses” that are now leading to major advances in the clinical care of patients. Multiple exciting presentations in the biggest rooms at ASH were packed to the hilt as attendees learned how these approaches are now helping patients. The treatments have not been perfected, and we still have much to learn as we seek to help as many patients as possible. Nevertheless, the enthusiasm for these approaches has been rejuvenated – indeed multiplied several fold. The naysayers are nowhere to be found (with some now saying “I knew it would work all along!”).

More specifically…

• Advances in our understanding of how cancer hides from the immune system have resulted in new treatments (including antibodies that mediate “immune checkpoint blockade”) that, in some patients, can unleash the ability of the immune system to fight and reject a cancer.
• We can successfully retarget immune system cells towards cancer cells by either reprogramming them genetically to recognize the cancer (CAR T cells), or by using antibody molecules that retarget them to fight the cancer (bispecific antibodies).
• New antibody-drug conjugates cancer deliver incredibly potent chemotherapy drugs directly to cancer cells.
• Gene therapy involving use of a virus to carry a gene to the liver results in liver cells producing a protein that is central to blood clotting, thereby reversing a type of hemophilia.

The basic concepts are no different from where they were 25 years ago, but technical advances and persistence have led to new scientific understandings, new treatments and new levels of acceptance and excitement.

So – a message to those researchers and clinicians who are a generation behind me, and are just starting to attend the ASH conference. Don’t be frustrated because no one seems interested in your idea or progress seems to slow. Don’t get frustrated if many of your colleagues at ASH seem more interested in munching on pretzels than in stopping by your poster to talk. And finally, if I tell you to give up on the idea, and that the concept you want to explore is a “failed hypothesis”, don’t listen to me. If it is a good idea, keep at it. Yesterday’s ignored and failed hypothesis could very well be tomorrow’s breakthrough.