The Most Significant Cancer Research Advances of the 2010s – Dana-Farber Cancer Institute

It was a decade that began with the electrifying results of a clinical trial for a revolutionary new cancer therapy and ended with a Nobel Prize in Medicine for very different cancer-related research. In between those dramatic bookends, the 2010s were packed with progress, with discoveries leading to the FDAs 2017 approval of the first CAR T-cell therapy. Additional approvals would follow.

The 2010s started with clinical trial results centered on the use of checkpoint inhibitors, drugs that unleash a powerful immune system attack on cancer cells. The results founded on decades of research by scientists like Dana-Farbers Gordon Freeman, PhD helped usher in a new era of cancer immunotherapy.

Checkpoint blockersare transformational, Laurie H. Glimcher, MD, president and CEO of Dana-Farber and a prominent immunologist, said back in 2017, but they are only the tip of a proverbial immunotherapy iceberg.

On the other side of the last 10 years in cancer research was the Nobel Prize in Medicine, shared by Dana-Farbers William G. Kaelin, Jr., MD, for discoveries into the mechanism that enables cells to sense and adapt to changes in oxygen abundance research that has already led to exciting new treatments for cardiovascular disease and cancer.

As cancer research pioneer and Dana-Farber founder Sidney Farber, MD, said back in 1965, I have never accepted the incurability of cancer. And I have remained hopeful, not because of wishful thinking thats not progress but because of the factual evidence of progress. There is no such thing as a hopeless case.

Aside from these prominent discoveries, what were the most significant advances in cancer research and treatment? Heres what scientists and clinicians from around Dana-Farber said.

William Hahn, MD, PhD, Chief Research Strategy Officer

The sequencing of human cancer genomes over the past decade has demystified the genetics of cancer. We now have a blueprint of cancer genes in every type of cancer and information about the frequency and type of mutations that occur. This has revealed new genes and pathways important for cancer development and in some cases has already led to new approved cancer therapies.

In addition, geneticallysequencing tumor tissue samples guides the therapeutic agents selected for asubset of cancer patients. This tailored approach, termed precision medicine,selects patients most likely to respond and spares those that are unlikely torespond from untoward side effects. Recent discoveries that its possible tosequence DNA in the blood to detect cancers provide hope that this approach canbe used to identify cancers earlier and follow the response to therapy.

Through the study of rare cancers, we have identified mutations in genes that regulate the epigenome, the cells machinery for activating and deactivating genes. These studies have revealed that these same pathways are dysregulated in many common cancers and play key roles in cancer pathogenesis and resistance to therapy.

Sapna Syngal, MD, MPH, Director of Research, Center for Cancer Genetics and Prevention

The realization that upto 10% of many solid tumors have an inherited genetic basis provides us with agreat opportunity for precision prevention and early interception.

Scott Armstrong, MD, PhD, President, Dana-Farber/Boston Childrens Cancer and Blood Disorders Center

Were now able to identify several premalignant states that significantly increase peoples risk of developing certain hematologic cancers. Individuals with clonal hematopoiesis of indeterminate potential (CHIP), for example, have certain genetic mutations in their blood-forming stem cells that are associated with leukemia.

People with CHIP dont have symptoms of disease, but their risk of developing a blood cancer such as leukemia is 10 times higher than average and their risk of cardiovascular disease is elevated as well. Being able to identify high-risk individuals means we can begin to think about early-intervention strategies to prevent these cancers from developing an active area of research.

Ursula Matulonis, MD, Chief, Division of Gynecologic Oncology

The introduction of drugs known as PARP inhibitors has had a major impact on the treatment of ovarian cancer, and now they are showing effectiveness against other cancers including breast and pancreatic. PARP inhibitors work by blocking one of the key routes by which cells repair damaged DNA and are especially effective in cancers with existing DNA-repair deficiencies such as those harboring BRCA mutations.

Also, better understanding of the genomics of gynecologic cancers the set of genetic mutations within the cancer cells is transforming the way we approach treatment and prevention. Its now widely recognized that women with ovarian cancer, regardless of age, histology type, or the stage at which their cancer is diagnosed, should undergo genetic testing. A percentage of them will have a predisposing mutation in one of the BRCA genes. Women with newly diagnosed endometrial cancer should have their cancer tested for mismatch repair deficiencies, which interfere with the proper copying of DNA during cell division.

The presence of these genetic features not only influences the treatment patients receive, but, because they can be inherited, often enable us to identify family members who are also at risk and can benefit from more intensive monitoring or preventive treatment.

Richard Stone, MD, Program Director in Adult Leukemia

Morethan 10 drugs have been approved for acute leukemia in the past three years,whereas there had been very few new agents in the previous 25 years.

DNA sequencing of patients leukemia cells to identify mutations is being used to help guide treatment decisions.

Eric Winer, MD, Senior Vice President for Medical Affairs and Faculty Development; Chief, Division of Breast Oncology

In the treatment of breast cancer, we now know for a certainty that one size does not fit all. This allows us to personalize therapy to a much greater extent than ever before. In some patients, this means we can treat them with less-intensive therapy and still obtain excellent results. Others may require more extensive therapy or benefit from a different therapeutic approach. For all patients, this means better, more effective care, fewer side effects, and, for many, a longer life.

Kimberly Stegmaier, MD, Vice Chair of Pediatric Oncology Research

There have been multiple approvals of new targeted drugs in adult acute myeloid leukemia (AML) in the past two years, as well as TRK inhibitor approval for adult and pediatric patients with TRK fusion-positive cancers.

Bruce Johnson, MD, Chief Clinical Research Officer

Addingthe kinase inhibitor midostaurin to standard chemotherapy significantlyprolonged overall and event-free survival in patients with acute myeloidleukemia whose cancer cells have a FLT3 mutation.

Enzalutamide,an androgen receptor inhibitor, was associated with significantly longer progression-freeand overall survival than standard care in men with metastatic,hormone-sensitive prostate cancer receiving testosterone suppression.

Dana-Farberscientists reported on the feasibility, safety, and immunogenicity of apersonalized cancer vaccine that caused immune T cells to recognizecancer-related neoantigens on tumor cells. These results have promptedfurther development of a neoantigen vaccine approach.

Nadine Jackson McCleary, MD, MPH, Gastrointestinal Oncologist

Weve made strides in ensuring that evidence from cancer research studies actually makes its way into clinical practice. For too long, research findings often seemed to remain in academia without being translated to clinical medicine.

Professional and patient advocacy organizations have undertaken a variety of steps to not only implement these advances in the clinical setting but also to make sure theyre sustainable. For example, organizations such as the American Society of Clinical Oncology (ASCO) and cooperative research groups regularly inform the broader public about research results and work at the state and federal level on behalf of patients. The development of implementation science is having a sizable impact on clinical practice.

Were also making progress in improving equity in cancer care delivery. Where equity issues have traditionally involved issues such as race, gender, and socioeconomic status, were broadening the focus to include considerations of gender identity, patient location (where patients receive treatment may affect their outcome), and treatment of the very youngest and oldest patients. These efforts will help ensure that advances in cancer medicine reach all populations.

Toni Choueiri, MD, Director of the Lank Center for Genitourinary Oncology

An important ongoing approach is liquid biopsies obtaining tumor-related DNA in the blood as a means of early cancer detection. Liquid biopsies also have the potential to detect minimal residual disease in the body following surgery to predict the risk of relapse.

Rameen Beroukhim, MD, PhD, Physician-Scientist in Neuro-Oncology

This decade is the first in which targeting collateral vulnerabilities in cancer cells has become an important strategy. Most efforts at treating cancer focus treatment on the genetic changes within cells that cause them to become cancer. But along the way, many genes that have nothing to do with cancer are also affected, and scientists have found that targeting these genes on which the cancer cells depend can be an effective way of attacking cancer. Immunotherapy, for example, detects cancer cells based on this collateral damage.

I predict that targeting collateral vulnerabilities will become increasingly important in future decades. Another recent strategy is based on the emerging technology of protein degradation, which removes cancer-related proteins from cells rather than simply binding to these proteins to inhibit their activity.

Link:
The Most Significant Cancer Research Advances of the 2010s - Dana-Farber Cancer Institute