On May 14, 2018, JALBCA held its annual Awards Presentation Dinner at the Ziegfield Ballroom in Manhattan. Hon. William C. Thompson, a founding member and long-time Treasurer of JALBCA, was celebrated. Hon. Thompson, or Willie as everyone knows him, is a former Justice of the Appellate Division, Second Department, and had been married to Justice Sybil Hart Kooper, who died of breast cancer in 1991. It was her death that impelled a number of judges and lawyers in New York to form JALBCA. Willie’s son, William Thompson, Jr., introduced his father, regaling us with stories of his father’s rise to prominence – first as a State legislator and then as a judge.
The Honorable Janet DiFiore, Chief Judge of the New York Court of Appeals and Honorary President of JALBCA, presented the Leadership Achievement Award to the Honorable Paul G. Feinman, Associate Judge of the New York Court of Appeals. Judge Feinman spoke about his beloved cousin’s traumatic battle with breast cancer and the vital need for legal assistance for breast cancer victims. JALBCA’s special guest speaker, Yvette Quow, brought Judge Feinman’s words to life for a rapt audience, explaining how her attorney at The Judith S. Kaye Project at The Family Center (a JALBCA grantee) saved her home and her life following a devastating experience with breast cancer.
Former Co-President Sharon Nelles, assisted by Dinner Co-Chairs Richard Edlin and Maura Miller, obtained generous pledges from attendees to fund mobile mammography vans and other JALBCA projects.
The Dinner ended on an inspiring note when we presented The Maite Aquino Memorial Grant Award to the Citi Legal Department, accepted by Ellen Slipp, Managing Director and ICG Litigation Counsel. Ellen summed up the evening with moving words about her sister’s fight against breast cancer, a poem and an expression of Citi’s unwavering support for providing legal services to those in need.
Please save the date for next year’s Awards Presentation Dinner on May 6, 2019.
The Persephone Trial – Can Herceptin Treatment Be Shortened on Early Breast Cancer?
A study paid for by the British government, and reported by the New York Times on May 16, 2018, was described by Dr. Helene Earl, one of the study’s authors, as the first one to show that women with early-stage breast cancer may be able to safely cut back on Herceptin. Dr. Helena Earl is with the University of Cambridge in Britain. Dr. Earl was quoted as saying, “Here we are asking the question whether less is more.” The study had not yet been published in a medical journal, and some experts reserved judgment until the data have been peer-reviewed. The article, “Good News on Early Breast Cancer: Herceptin Treatment Can Be Shortened”, can be found at https://www.nytimes.com/2018/05/16/health/breast-cancer-herceptin-genentech.html.
This trial is one of several efforts in cancer research to explore whether the adverse side effects of treatment can be lessened without reducing efficacy – e.g., avoiding chemotherapy based on tests of gene activity in tumors, lessening the dosage or duration of treatment, or monitoring early cancers without immediate intervention such as surgery. It was noteworthy that the study was financed by the government rather than a pharmaceutical company, since companies are not incentivized to conduct research that could yield results that justify a reduction in the use of their product, thereby hurting their bottom line to the dissatisfaction of their shareholders.
The cited study has not changed the current standard of care. But, as explained in the article, there are recognized side effects to Herceptin – such as congestive heart failure, the risk of which increases the longer the drug is taken. Hence, a shorter treatment period would be beneficial. Reportedly, only15 percent of women with early breast cancer have tumors that respond to Herceptin. These tumors are especially aggressive because they have high levels of the HER2 protein, a protein which promotes cancer growth.
The women in the Persephone study had stages 1, 2 and 3 breast cancer – early-stage, meaning it had not spread to bones or organs. The findings do not apply to women with stage 4 breast cancer, more advanced disease that has spread, who need a longer course of treatment. After peer review and further analysis of the study results, researchers may be able to conclude whether or not there are subgroups of patients with specific levels of risk that would signal different advice about Herceptin.
The study included 4,089 women in Britain who were picked at random to take the drug for six or 12 months, along with standard chemotherapy. The women were 23 to 82 years old, with a median age of 56. They were followed for a median of more than five years. After four years, the disease-free survival rate was 89.4 percent in those treated for six months, and 89.8 percent in the 12-month group. Disease-free survival means they had no signs of breast cancer; the lack of difference between the two groups suggests that their overall survival should be equal as well. The study participants will be followed for 10 years.
2018 ASCO Annual Meeting
From June 1-5, 2018, the American Society of Clinical Oncologists (ASCO) held its annual meeting in Chicago. The meeting focused on “Delivering Discoveries: Expanding the Reach of Precision Medicine.” To access the meeting’s scientific news, one can visit ASCO’s patient education website – https://cancer.net – which offers complete coverage of news highlights from the event.
Organs-on-Chips – A New Technology
Currently, to obtain FDA approval of a drug, various forms of animal and cell testing are first required. Even after passing the pre-clinical cell or animal testing, approximately 30 percent of candidate drugs have failed because of toxicity. This occurs despite promising pre-clinical studies in animal models. Approximately 60 percent of candidate drugs fail due to lack of efficacy. A substantial amount of time and money is consumed through this process because it takes an average of 12 years and $359 million dollars to obtain FDA approval. It is estimated that close to 75 percent of pharmaceutical research and development expenditures are invested in drugs that do not make it to market. In the end, this drug development paradigm is problematic.
As summarized by the Wyss Institute for Biologically Inspired Engineering at Harvard University (led by Founding Director and Wyss Core Faculty member Donald Ingber), cancer researchers are aware of the need to move past animal experimentation for cancer research. They understand that generating human tumors in mice by injecting cancer cell lines under the skin does not replicate how tumors normally emerge and spread to specific organs in the human body, nor how they respond to anti-cancer drugs. Thus, researchers now inject tumor cells into the same organ sites where they originated in humans, i.e., “orthotopic” sites. Orthotopic tumors, such as those created by injecting breast cancers into the mammary fat pads of mice, exhibit growth and metastatic behaviors more like those seen in patients but, even so, these are dissimilar from the human organ environments. In these orthotopic animal models, researchers are unable to visualize how tumor cells grow, move and respond to therapeutics and this restricts researchers’ ability to understand how different organ microenvironments influence tumor behavior. In turn, it inhibits the ability to develop better drugs. Animal studies are notoriously poor predictors of how a given drug will behave in humans. Similarly, conventional cell culture models with cell lines in dishes do not actually reflect cancer in the human body and have limited predictive value for drug response.
The pharmaceutical industry is moving towards personalized medicine. With personalized medicine, drugs are directed against biological defects underlying the tumor. Researchers search for drugs that specifically target the pathophysiology of an individual patient. To succeed, they need more knowledge about the molecular and cellular mechanisms of tumor development and metastasis, and also about the interaction between cancer cells and the body’s immune system. Hence there is a need for human model systems of cancer to replace conventional testing, i.e., animal models and conventional cell culture models.
Organs-on-Chips: What are They?
Companies are pioneering the modeling of tumors on microfluidic chips – also known as “human organs-on-chips” or “tissue chips” – that are based on primary cancer tissue and will ultimately incorporate the human immune response. As the name suggests, each chip is modeled to replicate the characteristics of a human organ. Two crossing microchannels for liquid transport are separated by a porous membrane on both sides of which cells can be cultured. The resulting organ-on-chip type human cancer models can be used for research of cancer growth and metastasis, drug target discovery (including for immunotherapy), testing drug compounds, and for associated companion diagnostics.
Testing for the chip began with the “Tissue Chip for Drug Screening” program, which was launched by NIH Institutes and Centers as well as pharmaceutical companies in 2012. Traditional pre-clinical cell trials tested drugs on cells that were isolated in a petri dish. Researchers were unable to see what effects the drug would have in an interactive environment in the human body. The new “human organs-on-chips” technology combines 3D configurations of human cells and microfluidic techniques, which improves the predictive value of clinical testing. The new chips, the size of AA batteries, are designed to re-create a dynamic microenvironment, which allows researchers to get a more accurate picture of how drugs would affect the human body. Through its Tissue Chip for Drug Screening program, the National Center for Advancing Translational Sciences (NCATS), along with other NIH Institutes and Centers, the Defense Advanced Research Projects Agency and the Food and Drug Administration, leads the development of organs-on-chips.
Anticipated Benefits of Organs-on-Chips
Human organs-on-chips have significant benefits. First, since they can replicate characteristics of organs, researchers will be able to test early on whether certain drugs are toxic to humans. Animal testing and cell clinical trials often cannot accurately predict reactions of the human body such as liver failure. As previously noted, under the current process, 30 percent of drugs that reach human clinical trials fail because they are found to be toxic. The development of “human organs-on-chips” would pick up the toxic effects drugs have on human organs at an earlier stage and prevent trial patients from having to suffer the adverse effects of these trial drugs. Second, the micro-chips have the potential to reduce drug development costs and failure rates and reduce time-to-market. Finally, this new technology could reduce reliance on animal testing and, thereby, avoid the ethical issues presented by, and cruelties of, such testing. Organs-on-chips would support the 3Rs – reduction, refinement and replacement of animal experimentation. In sum, it would revolutionize drug development, disease modeling, and personalized medicine.¹
1. Sources for this article include the following:
1. About Tissue Chips, https://ncats.nih.gov/tissuechip/about.
2. Bob Woods, It sounds futuristic, but it’s not sci-fi: Human organs on-a-chip, https://www.cnbc.com/2017/08/14/fda-tests-groundbreaking-human-organs-on-a-chip.html.
3. Linda H.M. Van de Burgwal, et al., Hybrid business models for ‘Organ-on-a-Chip’ technology: The best of both worlds, PHARMANUTRITION, Vol.6, Issue 2 (June 2018), 55-63, https://www.sciencedirect.com/science/article/pii/S2213434417301147.
4. Lung Cancer Research Gets A Breath of Fresh Air, Oct. 10, 2017, https://wyss.harvard.edu/wyss-institute-models-a-human-disease-in-an-organ-on-a-chip/.
5. Wyss Institute, Wyss Institute Models a Human Disease in An Organ-On-A-Chip, Nov 7, 2012, https://wyss.harvard.edu/wyss-institute-models-a-human-disease-in-an-organ-on-a-chip/. See also First study of radiation exposure in human gut Organ Chip device offers hope for better radioprotective drugs, Feb. 14, 2018, https://wyss.harvard.edu/a-gut-reaction-on-a-chip/.
6. Cancer on Chip, https://www.hdmt.technology/cancer-on-chip. hDMT is the acronym for the Institute for Human Organ and Disease Model Technologies, which describes itself as a precompetitive non-profit technological R&D institute, initiated in the Netherlands. hDMT is a public-private consortium of nine founding partners, including the three Universities of Technology (Twente, Eindhoven, Delft), the Leiden University and University Medical Centre, Erasmus Medical Centre, the Hubrecht Institute, and two companies Genmab and Galapagos.
7. Wyss Institute, Human Organs-on-Chips, https://wyss.harvard.edu/technology/human-organs-on-chips/.
8. National Center for Advancing Translational Sciences (NCATS), Tissue Chip for Drug Screening, https://ncats.nih.gov/tissuechip.
9. Suzanne Fitzpatrick, Organs-on-Chips’ Technology: FDA Testing Groundbreaking Science, https://blogs.fda.gov/fdavoice/index.php/2017/04/organs-on-chips-technology-fda-testing-groundbreaking-science/.
10. Wyss Institute, Predicting Side Effects Before They Happen, https://wyss.harvard.edu/predicting-side-effects-before-they-happen/.
11. Everything you always wanted to know about organ-on-chip technology and hDMT (but were afraid to ask,) https://www.hdmt.technology/download/?id=2300&download=.