{"id":2243,"date":"2023-05-13T03:55:36","date_gmt":"2023-05-13T03:55:36","guid":{"rendered":"https:\/\/magazines.uthscsa.edu\/cancer-center\/?p=2243"},"modified":"2023-05-19T19:00:17","modified_gmt":"2023-05-19T19:00:17","slug":"the-biology-of-cancer","status":"publish","type":"post","link":"https:\/\/magazines.uthscsa.edu\/cancer-center\/2023\/05\/13\/the-biology-of-cancer\/","title":{"rendered":"The biology of cancer"},"content":{"rendered":"

\u201cWhat inspires me to fight cancer are the remarkable advances in treatment, all of which we owe to cutting-edge basic research carried out by brilliant scientists here and all over the world. With a better understanding of the disease, this is a battle that can be won on many fronts.\u201d <\/em><\/h3>\n
\u2014\u00a0<\/em>Sandeep Burma, PhD<\/strong>,\u00a0<\/span>Professor of Neurosurgery and Biochemistry and Structural Biology;\u00a0Mays Family Foundation Distinguished Chair in Oncology;\u00a0Vice Chair for Research, Department of Neurosurgery<\/h5>\n

<\/h2>\n

Glioblastoma recurrence and clues to blunt it<\/strong><\/h2>\n

Radiation therapy after surgery is the primary treatment for most glioblastoma patients. \u201cIonizing radiation works quite effectively, up to a point,\u201d said Sandeep Burma, PhD, professor of neurosurgery and biochemistry and structural biology at the Mays Cancer Center.<\/p>\n

\u201cSurgical resection of the tumor improves survival by approximately six months. Adding ionizing radiation extends survival to a year or even more. Unfortunately, the tumors always recur, and once they do, they are generally not responsive to therapy,\u201d said Burma.<\/p>\n

Burma and a team of investigators at the Mays Cancer Center are studying companion treatments to see if any can eliminate this Jekyll and Hyde property of ionizing radiation. The team\u2019s research, first published in Cancer Research<\/em>, suggests that the irradiated margin of healthy brain cells becomes a fertile microenvironment for cancer regrowth.<\/p>\n

The role of senescence<\/strong><\/p>\n

If a cell is old, stressed or damaged by radiation, for instance, it may enter a state in which it can no longer divide. This is senescence. Senescence normally serves as an anti-cancer barrier by preventing such damaged cells from proliferating. But during the last decade, it has become clear that senescent cells can accelerate cancer progression by spewing tumor-promoting factors.<\/p>\n

\u201cWhen we irradiate a brain tumor, normal cells like astrocytes in the vicinity of the tumor senesce and just sit there, spitting out growth factors that seem to drive tumor recurrence,\u201d Burma said.<\/p>\n

Radiation therapy of glioblastoma traditionally targets not only the tumor, but a two- to three-centimeter margin of normal brain tissue around it. This is done because glioblastoma cells are so infiltrative. Burma and his colleagues now believe that the irradiated margin of healthy brain cells becomes a fertile microenvironment for cancer regrowth.<\/p>\n

Clearing out senescent cells<\/strong><\/p>\n

The team also administered agents to clear senescent cells. This treatment, still in its infancy, is called senolytic therapy, and it is being tested in Alzheimer\u2019s disease, COVID-19 lung disease and a host of other disease conditions.<\/p>\n

\u201cIn our study, we showed that by using senolytics to clear senescent cells after radiation, we can slow down the growth of implanted tumor cells and improve survival,\u201d Burma said.<\/p>\n

Findings suggest that following radiation, adjuvant senolytic therapy could be a one-two punch against glioblastoma recurrence.<\/p>\n

Eventually, a radiation-senolytic combination could be an answer long sought by oncologists, families and patients alike to blunt glioblastoma recurrence.<\/p>\n

\n

Studies show promise for improving bladder cancer survival<\/strong><\/h2>\n

Bladder cancer is the fourth most-common type of cancer in men. In patients with high-grade cancer in the lining of the bladder \u2014 also called non-muscle invasive bladder cancer \u2014 cancer often comes back within a year following standard treatment. Although there are several approved treatments, none have significantly improved survival rates without serious side effects.<\/p>\n

In a study published in The Lancet Oncology<\/em>, Mays Cancer Center urologic oncologist and study site principal investigator Robert Svatek, MD, and his team evaluated a novel immunotherapy called nadofaragene firadenovec (NF) gene therapy that may offer new hope.<\/p>\n

\u201cThis product is remarkable as one of the first virus-delivered gene therapies to treat cancer,\u201d Svatek said. \u201cNF is a virus that has been altered to transport a genetically modified protein called interferon alfa-2b. Once in the bladder, interferon alfa-2b prompts the cells in the lining of the bladder to make more of this protein to fight cancer, strengthening the body\u2019s immune response.\u201d<\/p>\n

By piggybacking the protein and delivering it with a virus in a liquid placed in the bladder through a catheter, the protein is contained in the bladder for an hour \u2014 long enough to provide a significant immune response.<\/p>\n

\u201cNF has fewer and less serious side effects than other treatments approved for this type of cancer. NF also allows patients to avoid surgery to remove the bladder, which is the next treatment to consider if the current standard treatment fails,\u201d said Svatek.<\/p>\n

About 75% of bladder cancer cases are classified as non-muscle invasive, which means the cancer affects the tissue lining the inner surface of the bladder, but not the bladder muscle.<\/p>\n

According to the study, 53.4% of participants receiving NF were free of cancer at three months and 45.5% of patients continued to be cancer-free for at least 12 months.<\/p>\n

The phase 3 study included 153 patients from 33 U.S. institutions, including the Mays Cancer Center. Svatek and his team will continue to follow patients for four years to learn more about how they respond long term.<\/p>\n

Understanding survival discrepancies<\/strong><\/p>\n

In another study published in Bladder Cancer<\/em> by researchers at the Mays Cancer Center, bladder cancer was found to be more aggressive and more advanced in residents of South Texas than in many parts of the country.<\/p>\n

According to the study\u2019s findings, the disease is also deadlier in Hispanics and women, regardless of where they live nationwide.<\/p>\n

For this study, the research team compared bladder cancer cases in the Texas Cancer Registry with cases in the Surveillance, Epidemiology, and End Results (SEER) program. SEER, which collects data on cancer cases from various locations across the U.S., does not include Texas statistics.<\/p>\n

\u201cAlthough South Texas and Texas had lower bladder cancer incidence rates than SEER, the region and state had significantly worse five-year survival rates for bladder cancer compared to SEER. This was regardless of gender,\u201d said the study\u2019s first and corresponding author Shenghui Wu, MD, PhD, assistant professor of population health sciences at UT Health San Antonio.<\/p>\n

\u201cWe also found that Latinos, both men and women, had lower incidence but worse survival than non-Latino whites in each geographical area,\u201d Wu said. \u201cAnd women had significantly lower bladder cancer incidence but worse survival rates than men, regardless of race or ethnicity, in each area.\u201d<\/p>\n

Svatek, a study coauthor, said the findings reveal the complex variations among diverse groups in their responses to cancer. The Texas population, which is 40% Hispanic, \u201cis uniquely different than the rest of the United States in the biology of bladder cancer,\u201d Svatek said. \u201cIt means we really need to understand what is going on locally and study our patients to understand why there is a difference.\u201d<\/p>\n

Smoking contributes to bladder cancer development, but other factors aren\u2019t known. The study authors note that residents in South Texas have lower per capita personal incomes; higher rates of unemployment, poverty and lack of insurance; lower educational attainment; less access to health care services; and higher obesity prevalence than the state as a whole, all of which may uniquely impact both incidence and survival rates for cancer patients.<\/p>\n

\n

Detecting cancer\u2019s spread before it happens<\/strong><\/h2>\n

Cancer that spreads to another area of the body is typically less treatable as the primary tumor from which it has originated. Survival from metastatic disease is generally poor.<\/p>\n

But what if a daily or weekly blood sample could monitor each patient\u2019s risk of metastasis, indicating the need for aggressive therapy before cancer spread is established?<\/p>\n

That\u2019s the goal of researchers at the Mays Cancer Center. In the journal Cancer Research<\/em>, authors including Maria E. Gaczynska, PhD, and Pawel Osmulski, PhD, report that blood-borne seeds of cancer, called circulating tumor cells (CTCs), have specific properties that can be measured.<\/p>\n

For example, CTCs are sticky and glom onto other cells called macrophages while hurtling through the bloodstream. Macrophages are infection-fighting cells that can be either pro- or anti-inflammatory.<\/p>\n

The study, conducted in human prostate cells provided by the Mays Cancer Center, indicated that the presence of macrophages, along with properties such as stickiness, can be an accurate biomarker of risk for metastasis.<\/p>\n

\u201cWhat is completely new, what we found here, is that both pro- and anti-inflammatory macrophages can be bad for the patient,\u201d Gaczynska said. \u201cBoth can help circulating tumor cells to survive.\u201d<\/p>\n

\u201cActually, this is like a crystal ball,\u201d said Gaczynska. \u201cWhen we are looking at the nanomechanical properties, and when we are asking how many macrophages there are, we can tell if this patient is at risk of metastasis very soon.\u201d<\/p>\n

The finding about the role of macrophages in cancer is a key building block discovery.<\/p>\n

\u201cBecause the majority of cancer patients die of metastasis, this is of very high medical relevance,\u201d Osmulski said. \u201cThe interactions between CTCs and macrophages can be the target of anti-metastasis drugs.\u201d<\/p>\n

Current studies use an atomic force microscope at UT Health San Antonio and are technically demanding, but the researchers seek to streamline the process to make it a bedside diagnostic.<\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

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