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Cancer advances: Dr. William G. Nelson discusses genome sequencing and immunotherapy

Dr. William G. Nelson is the director of the Johns Hopkins Kimmel Cancer Center, in Baltimore, MD, and a professor of oncology. In this article, he discusses two rapidly developing approaches to cancer treatment: Genome sequencing and immunotherapy.

Dr. Nelson is also the editor-in-chief of Cancer Today, the magazine of the American Association for Cancer Research (AACR). What follows is a lightly edited version of Dr. Nelson’s response when we asked him which areas of cancer research he was most excited about. He particularly focuses on data presented at this year’s AACR Annual Meeting, held virtually.

Cancer medicine is in the midst of a fast-paced transformation that is starting to produce clear improvements in disease outcomes, with cancer death rates down 27% over the past 20 years.

Some of the decline in cancer deaths can be attributed to smoking cessation and some to the broader adoption of established cancer screening approaches, but innovations arising from cancer research have really started to impact cancer care.

Researchers have long known that all cancers fundamentally arise as a consequence of acquired defects in genes and in gene function that propel rogue cells in the body to replicate wildly.

Now, with advances in genome sequencing technologies, all of the aberrant genes in any cancer can be inventoried, allowing existing treatment approaches to be tailored to individual cancer cases. This opens the door to the discovery and development of scores of new cancer treatments aimed directly at the products of defective genes.

For example, during the Clinical Trials Plenary Sessions at the AACR Annual Meeting 2021, researchers presented data from a phase 3 trial in patients with relapsed, slow-spreading non-Hodgkin lymphoma.

The researchers showed that combining the standard-of-care drug rituximab with copanlisib — a therapeutic that targets the PI3K cell-signaling pathway, which lymphoma cells rely on for survival — could reduce the risk of disease progression or death by half, compared with a placebo and rituximab.

In another trial, selpercatinib, a first-in-class, highly selective, and potent RET kinase inhibitor that is approved to treat some lung and thyroid cancers, showed promise for several other cancer types, including pancreatic cancer, colon cancer, and breast cancer.

Genome sequencing approaches are also increasingly used to detect cancer DNA shed into blood and body fluids, giving rise to what will be a new generation of cancer screening and monitoring tests.

Several presentations from the meeting showcased multicancer early detection tests that utilize machine learning and cell-free DNA from liquid biopsy samples to search for abnormal patterns of DNA methylation.

Few areas of cancer research have created as much excitement as deciphering ways to harness the potential of the immune system to fight cancer. The immune system can discriminate “friend from foe” anywhere in the body, recognizing bacteria and viruses as foreign, even distinguishing infected, diseased cells from noninfected, healthy cells.

What has become clear is that the immune system “sees” cancer cells as different from normal cells but all too often fails to respond in such a way as to eliminate the threat. Some cancers, like certain melanomas, lung cancers, and others, appear to hold the destructive power of the immune system in check as they grow ever more malignant.

For these cancers, immune checkpoint inhibitors can unleash the immune system to attack the cancer cells, providing stunning benefits when used in cancer treatment.

A type of immunotherapy called CAR T-cell therapy is currently approved to treat certain leukemias, lymphomas, and multiple myeloma, and researchers are trying several different approaches to improve their efficacy and durability and to expand their applicability to solid tumors.

Cancer vaccines are another form of immunotherapy that indirectly attack cancer by training a patient’s immune cells to recognize and destroy cancer cells. Oncolytic virotherapy utilizes a virus to selectively infect and destroy cancer cells; the resulting cancer cell debris can also trigger an antitumor immune response.

Clinical trial data from such approaches were discussed at the AACR Annual Meeting.

In the future, ongoing cancer immunology research will provide even more opportunities to activate the immune system against all types of cancer, driving cancer medicine toward more and more cancer cures.

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