AACR 2015: Progress, Promises and Future Challenges in Cancer Research

The American Association for Cancer Research (AACR) hosted its 106th Annual meeting April 18-22 in Philadelphia, PA.

AACR’s annual meeting, the largest cancer research gathering in the world, attracts basic and clinical scientists, as well as representatives from industry, patient advocacy and governmental regulatory agencies. This year’s meeting attracted more than 19,200 attendees and included over 700 presentations covering the spectrum of cancer research from population science, cancer biology and clinical trials to survivorship.

The first thing that strikes anyone attending the meeting is the sheer enormity and diversity of the program.   While it is physically impossible to attend all the talks, posters and events, BCRF came away with a big picture of advances in breast cancer research as well as some the major challenges that lie ahead. Many BCRF grantees were in attendance, moderating sessions and presenting their research in oral presentations or poster sessions. BCRF congratulates the researchers who were recognized by AACR this year.

Nancy Davidson, MD, a BCRF grantee since 1998 and member of the BCRF Scientific Advisory Board, was elected 2015-16 President-elect of AACR. Other BCRF grantees who have led AACR are Carlos Arteaga (immediate past-president), Judy E. Garber, Geoffrey Wahl and Susan B. Horwitz.

Lewis Cantley, PhD. A BCRF grantee since 2009, Dr. Cantley was honored with the AACR Princess Takamatsu Memorial Lectureship for his discovery of the protein PI3K (Phosphoinositide- 3- Kinase). Today we know that the PI3K gene is one of the most commonly mutated genes in cancer.   Ongoing clinical trials are testing PI3K inhibitors in combination with other targeted therapies in breast and other cancers.

Elizabeth Jaffe, MD was honored with the AACR Joseph H. Burchenal Memorial Award for Outstanding Achievement in Clinical Cancer Research for her work in the development of immunotherapies for breast and pancreatic cancers.

Carlos Arteaga, MD. Outgoing AACR president and BCRF grantee since 2004, Dr. Arteaga was named a Fellow of the AACR Academy.

The theme of this year’s meeting was precision medicine, specifically translating discoveries in basic science to the development and clinical testing of molecularly targeted anti-cancer therapies.

Precision medicine is based on understanding the unique make-up of each individual to better understand his or her risk for disease as well as how best to treat the disease when it occurs. This has always been the goal of medical research, but technological advances in deciphering the tumor genome are bringing this vision into focus.  During an AACR –ABC News Twitter chat, Dr. Arteaga spoke of the ability to identify gene mutations in tumors as one of the major breakthroughs in cancer research. Examples of this include the HER2 protein in breast cancer, EGFR in lung cancer and BRAF in melanoma – all of which now have targeted therapies.

In spite of these discoveries, many challenges remain before precision medicine will be fully achieved. Clinical trials of targeted therapies in breast cancer often fail to achieve the desired results.  New approaches to the clinical trial process, as well as understanding why tumors become resistant to drugs and metastasize, are active areas of discussion and research.

It is widely recognized that no two breast cancers are alike. In addition to distinct subtypes of the disease that can be identified by molecular markers such as the estrogen receptor and HER2 protein,  there is a large degree of genetic diversity within individual tumors – intratumor heterogeneity –meaning that many tumors are made up of different tumor cells with unique gene mutations. We are just beginning to understand the many influences on and consequences of breast tumor heterogeneity, which will be an important piece in achieving precision medicine. Some of the things we’ve learned are:

– Breast tumors contain a variety of tumor cells with unique genetic profiles, some of which are capable of metastasis even before exposure to drugs.

– The genetic profile of a breast tumor changes during tumor progression and these genetic changes may predict the risk and location (organ) of metastasis.

– The environment around the tumor (tumor microenvironment) including immune cells can influence whether a tumor will respond to therapy or is likely to metastasize.

– One targeted therapy is not sufficient to treat most breast cancers.  Combination approaches of multiple targeted therapies with or without chemotherapy are likely to be more effective.

The technologies that have advanced the fields of genomics (the study of genes) and proteomics (the study of proteins) are the foundation of precision medicine and continue to evolve.  Emerging technologies in tumor metabolomics (the study of how tumors utilize energy) and liquid biopsy methods (measuring tumor proteins or genetic material in blood or other bodily fluids) will further enhance our ability to individualize screening and diagnosis, treatment and tumor monitoring.

One of the breakthroughs arising from molecular profiling of tumors is a better understanding of how the immune system interacts with tumor cells. The re-emergence of anti-cancer immunotherapies and the development of targeted drugs to enhance the body’s own immune response to cancer have generated much excitement.  Results from clinical trials in advanced lung cancer and melanoma have shown promise for a class of drugs called PDL-1 inhibitors. While response rates ranged from 15-20 percent of study participants, researchers are encouraged by a sustained effect in some patients who responded to the therapy.

Similarly, BCRF grantee Leisha Emens reported results from a phase I clinical trial of anti-PDL-1 therapy in patients with metastatic triple negative breast cancer (TNBC). Dr. Emens and others believe that TNBC may be a good candidate for immunotherapy because these tumors attract immune cells called lymphocytes,  a sign of an active immune response. PDL-1 inhibitors act to prevent the tumor cells from shutting down that response.  As with other studies, patient numbers and response rates in Dr. Emens’s study were low, but they present an opportunity to learn from those who show a prolonged response.  Studying the biology of the tumors in the “exceptional responders” may provide valuable insight into potential predictive biomarkers as well as clues on combination therapies that could improve response to immune-based strategies.

Other immune targets, as well as vaccine development and combination strategies, are being pursued in breast and other cancers. In closing remarks, Dr. Arteaga expressed measured hope for the current state of anti-cancer immunotherapy, emphasizing that much work needs to be done in identifying biomarkers of response and in making treatments affordable.

Looking to the future, the promise of precision medicine cannot be realized without an overhaul of the clinical trials process, which has not kept pace with technology. New trial designs such as Lung Map, ISP-2 and MATCH utilize tumor genomic information to match patients to targeted therapies with the opportunity to identify biomarkers that can be used to predict which patients will not respond to a particular drug. Last fall, the FDA hosted a workshop attended by scientists, pharmaceutical representatives and patient advocates that was focused on developing a biomarker-driven master clinical trial protocol to accelerate transfer of new drug discoveries to the clinic, particularly for metastatic breast cancer.

Note: BCRF was a co-sponsor of this important meeting along with AACR and the American Society of Clinical Oncology (ASCO).

Of course the most promising future is one without breast cancer. A study from the National Cancer Institute predicted a 50 percent increase in breast cancer incidence by 2030, tempering hopes for quick resolution. The study author, Philip Rosenberg, noted that most new breast cancer cases are expected to be estrogen-receptor (ER) positive, the most treatable form of breast cancer. Dr. Clifford Hudis, Chairman of the BCRF Scientific Advisory Board, lauded the report as a signpost to help breast cancer researchers plan ahead.

In order to plan effectively, scientists and clinicians must have the resources to continue their progress and to cultivate the next generation of scientist and clinicians to carry it forward. This has become increasingly challenging with declining government support for cancer research, which is about 25 percent of what it was in 2003.  This topic is mentioned  at every cancer conference. In an essay in the New York Times, former US Representative Newt Gingrich looked back to the 1990s when Democrats and Republicans in Congress came together to double the NIH budget for medical research. He called for renewed bi-partisan support of a similar effort for the fiscal year beginning in October. We are at a pivotal point in cancer research and it is up to all of us to show support for increased funding.

Note: September 18, 2015 is Rally for Medical Research Day on Capitol Hill.