A new report says those considering PSA screening need such quantitative information on risks and benefits of treatment if they are to make truly informed decisions. 

Yet leading guidelines do not provide specific estimates of risk.

The risks of adverse effects and complications from treatment for prostate cancer are substantial and continue for years after treatment ends. 

The largest comprehensive analysis reporting long-term risks from such treatment relative to the risks faced by a control group of untreated men has just been published in the journal JAMA Oncology.

In the 12 years following treatment, men whose initial treatment was a prostatectomy (removal of all or part of the prostate) had a risk of urinary or sexual complications more than seven times higher than that faced by untreated men. 

For men whose first treatment was radiotherapy, the risk of such complications was almost three times that of untreated men. Additionally, men in the radiotherapy group faced three times the risk of a bladder cancer diagnosis.

The report—by researchers from the SWOG Cancer Research Network, a clinical trials group funded by NCI, along with researchers from the NCI—argues that men need to have access to risk numbers such as these when deciding whether to even be screened for prostate cancer.

“This study throws down a major gauntlet to all physicians to give patients this information before they even begin the process of drawing a PSA test,” Ian M. Thompson Jr., of CHRISTUS Santa Rosa Health System and The University of Texas Health Science Center at San Antonio, and the paper’s senior author, said in a statement. A PSA test measures the blood level of a protein called prostate-specific antigen.

Roughly 30 million men in the U.S. are in the age range (55-69 years) for which the U.S. Preventive Services Task Force recommends discussing PSA testing with their doctor. Making an informed decision requires that they have a clear understanding of the magnitude of the potential risks and benefits of screening, and of each step that might follow it, which can include a biopsy and one or more treatments if prostate cancer is found.

One challenge in determining the risk of adverse effects from prostate cancer treatment is that for some of these conditions, such as erectile dysfunction, the incidence increases with age.

So, a true measure of risk can be determined only by comparing men treated for prostate cancer with untreated men of similar age in the general population. 

The JAMA Oncology study does just that.

“Past studies of prostate cancer treatment complications have had small sample sizes, limited follow up, or the absence of a valid control group,” lead author Joseph Unger, a biostatistician and health services researcher with SWOG Statistics and Data Management Center and associate professor at Fred Hutch Cancer Center, said in a statement. “Our study is distinguished by long follow-up, out to 12 years, looking at a broad spectrum of key complications. Critically, we were able to compare treated men to a representative control group of untreated men, which prior studies have not included.”

The issue of comparing to a valid control group is key, Unger noted: “Without this, it is difficult to understand the true magnitude of treatment complications.”

The researchers studied almost 52,000 men who had enrolled to one of two large NCI prevention studies—the Prostate Cancer Prevention Study and the Selenium and Vitamin E Cancer Prevention Trial.

To track participants’ diagnoses and treatment, they linked trial data to Medicare claims data, identifying 29,196 participants who had Medicare claims available and met other eligibility criteria. Among these, 3,946 had been diagnosed with prostate cancer, including 655 whose first treatment for the disease was a prostatectomy and 1,056 whose first treatment was radiotherapy.

Participants who had been diagnosed with prostate cancer but had not received treatment (because this cancer tends to grow slowly, many men choose active surveillance), along with those who had not been diagnosed with prostate cancer, served as an untreated control group for comparison.

For both groups, the research team examined the Medicare claims data for instances of 10 potential treatment-related complications and adverse effects: urethral stricture, placement of an artificial urinary sphincter (for severe incontinence), placement of a penile prosthesis, urinary incontinence, erectile dysfunction, radiation cystitis, radiation proctitis, bladder cancer, bladder cancer followed by cystectomy, and rectal cancer.

Those in the prostatectomy group had a 12-year risk of having at least one of these 10 complications that was more than six times (6.57) greater than the risk faced by untreated participants.

For men in the radiotherapy group, their 12-year risk of experiencing at least one of the 10 complications was 3.04 times greater than it was for those who had not been treated.

Moreover, after 12 years, those in the radiotherapy group were almost three times (2.78) as likely as untreated participants to have been diagnosed with bladder cancer, which is often of higher grade in those who previously had radiotherapy.

The authors argue that given the uncertain benefit of prostate cancer treatment for most patients, these findings highlight the importance of patient counseling before treatment and before screening.

They specifically recommend that quantitative information on the risks and benefits of prostate cancer treatment be included in national cancer screening and treatment guidelines. No national organization currently provides such quantitative information in their guidelines.

Researchers leading the SWOG S1712 clinical trial have found that adding ruxolitinib (Jakafi) to standard tyrosine kinase inhibitor treatment for patients with chronic-phase chronic myeloid leukemia significantly increased the percentage of patients who had a molecular response deep enough to warrant discontinuing treatment.

Results were presented at the European School of Haematology’s 26th Annual John Goldman Conference on Chronic Myeloid Leukemia held in Prague in September.

Kendra L. Sweet, a SWOG investigator at Moffitt Cancer Center who was principal investigator on the S1712 trial, delivered the results Sept. 27 as an oral presentation in the conference’s first scientific session, which is devoted to the meeting’s top-scoring abstracts.

“Treatment-free remission has become a common therapeutic goal for patients with CP-CML. In spite of this, only approximately 40% to 50% of CP-CML patients achieve molecular responses that are deep enough to qualify them for an attempt to discontinue TKI therapy,” Sweet said in a statement.

“In this study, the addition of ruxolitinib to TKIs resulted in significantly more patients with durable, deep molecular responses. Ultimately, this could lead to more patients successfully discontinuing treatment, which has been shown to significantly reduce healthcare costs and improve health-related quality of life.”

CML is often treated with a class of drugs known as tyrosine kinase inhibitors. But leukemic stem cells can hide from TKIs in a patient’s bone marrow. Preclinical data suggested that a drug

called ruxolitinib can alter the bone marrow microenvironment to sensitize these stem cells to TKIs.

Researchers from the SWOG Cancer Research Network, a cancer clinical trials group funded by NCI, hypothesized that adding ruxolitinib to TKI treatment would make TKIs more effective against leukemic stem cells, eradicating measurable residual disease in more patients.

In clinical trial S1712, they randomized 75 eligible patients with CML whose disease was still molecularly detectable on current therapy and who had been undergoing treatment with a TKI

for at least one year. All patients continued their TKI treatment, but one half of patients also had the drug ruxolitinib added to their treatment.

After 12 months of on-study treatment, all patients had their blood tested for molecular response, a highly sensitive test for RNA from a gene specific to leukemic cells. A score of MR4.0—considered a deep molecular response—indicates a reduction in this RNA to 0.01% or less of the baseline level. A score of MR4.5 indicates that no such RNA has been detected and is considered a complete molecular response.

The rate of S1712 patients scoring MR4.0 by 12 months was significantly higher on the ruxolitinib arm—46% versus 26% on the TKI-only arm. The rate of patients scoring MR4.5 at 12 months was significantly higher on the ruxolitinib arm as well—14% versus 3% on the control arm.

The addition of ruxolitinib also moved more patients to a remission deep enough that they were able to go off treatment. Two years after randomization, the proportion of patients who met the National Comprehensive Cancer Network guidelines criteria for being able to discontinue treatment was 29% on the investigational arm versus 11% on the control arm.

Toxicities were similar on the two arms. Two patients had grade 3 treatment-related adverse events on the ruxolitinib arm. On the TKI-only arm, three patients had grade 3 treatment-related adverse events and one patient had a grade 4 adverse event. Grade 1/2 anemia was more common in patients treated on the ruxolitinib arm of the trial.

Sweet’s team is now working to characterize which patients with CML are most likely to benefit from having ruxolitinib added to their TKI treatment. The authors conclude that further trials are warranted to test whether this combination could increase the percentage of these patients who move to treatment-free remission.

Study S1712 is supported by the NCI, led by SWOG, and conducted by the NIH-funded NCI National Clinical Trials Network.

Quitting smoking within six months after a cancer diagnosis adds an average of two years to a patient’s life, according to a study published inJAMA Oncology, 

With this information in hand, all cancer centers have an obligation to offer evidence-based smoking cessation to all patients, said Graham Warren, vice-chair for Research in the Department of Radiation Medicine. 

He is also the Mary Gilbreth Endowed Chair of Oncology, an MUSC Hollings Cancer Center researcher and senior author of a new paper that demonstrates a broad survival benefit of using evidence-based smoking cessation to help patients quit smoking as soon as possible after a cancer diagnosis.

“This is a survival benefit that we can achieve now. It isn’t something that we need to wait 10 years for trial results. If we miss patients now, well, they’ve missed the benefit that they would gain from it. So there’s an urgent responsibility to make this work,” Warren said in a statement. “It is important to make sure that we give everyone evidence-based care specifically to help them improve survival. This isn’t an optional thing.”

It’s well known that smoking after a cancer diagnosis decreases the effectiveness of treatment and increases the likelihood of certain side effects or complications. 

And some previous papers have looked at the survival benefit of quitting smoking in specific subgroups of patients with cancer, like those with lung cancer.

In this paper, Warren and his collaborators at MD Anderson Cancer Center were able to use data from the Tobacco Research and Treatment Program at MD Anderson to look at long term survival across more than 4,500 patients with a wide variety of cancers.

The records from this program were valuable because they regularly note a patient’s current smoking status and use of a structured evidence-based tobacco treatment program.

Too often, Warren said, cancer centers ask about a patient’s smoking status at diagnosis but don’t follow up throughout treatment to update the electronic health record.

With the detailed records from the TRTP, the researchers were able to subdivide patients into three groups: those who stopped smoking within six months of diagnosis, those who stopped between six months and five years after diagnosis and those who stopped more than five years after diagnosis. 

Quitting smoking after a cancer diagnosis improved survival across cancer as a whole, with the largest benefit among patients who quit within six months following diagnosis.

David Marshall, chair of Radiation Medicine and medical director of the Clinical Trials Office at Hollings, said the clear benefit of smoking cessation after diagnosis across all types of cancer places particular emphasis on the need to improve clinical treatment approaches for all patients. 

Marshall’s expertise is in prostate cancer and clinical trials, and he noted the impact of smoking on outcomes in prostate cancer.

“Most prostate cancer patients don’t die of prostate cancer. It is often smoking-related conditions that contribute to patient deaths,” he said.

Quitting smoking even among patients with non-tobacco related cancers can be one of the biggest contributors to improving overall survival.

Warren said these data likely represent the new gold standard cementing the survival benefit for supporting smoking cessation programs at cancer centers. Unfortunately, he said, while up to 90% of patients are asked about smoking, only about 40% of centers provide smoking cessation assistance.

“This isn’t like developing a new targeted agent. You don’t need new protocols or to buy new drugs,” he said. “If you understand the importance of this, you can start doing it this afternoon. The evidence is there. The treatments are there. It’s just a matter of getting clinicians to put it into practice and patients receiving evidence-based treatment.”

Raymond N. DuBois, director of MUSC Hollings Cancer Center, noted the significance for all types of cancer.

“This research shows in a very clear and straightforward manner what clinicians have often observed—that their patients who continue to smoke fare worse than those who are able to stop smoking,” DuBois said in a statement.

“This is a significant finding for people dealing with any type of cancer diagnosis, not just lung cancer, and for their doctors. Also, we have known that continued smoking after a cancer diagnosis weakens the immune system, making it harder for the body to fight off cancer cells.”

K. Michael Cummings, a colleague at Hollings with an extensive tobacco research record who has collaborated with Warren on other projects but not this paper, said the paper shows the clinical necessity of offering smoking cessation programs.

“Patients and family members need to be informed of the benefits of stopping smoking,” Cummings said in a statement. “Additionally, patients who smoke need to be given real help to stop smoking, recognizing that getting off cigarettes is not easy to do. Cigarette addiction is a chronic relapsing disorder so one-off interventions for patients are inadequate.”

While pancreatic cancer rates are rising in people under age 50, a new survey conducted by The Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute shows that most people continue to believe that pancreatic disease affects only elderly people—and that there is nothing they can do to reduce their risk.

For this survey, respondents were asked about risk factors for pancreatic cancer. More than half (53%) of adults under age 50 said they would not recognize the early signs or symptoms of the disease, and more than one-third (37%) believe there is nothing they can do to change their risk of pancreatic cancer. More than one third (33%) also believe only older adults are at risk.

“Pancreatic cancer rates, however, have been rising by about 1% annually, and we are seeing this disease in people who are in their 40s much more regularly. This is a concerning trend, and one for which research is needed to learn why,” Zobeida Cruz-Monserrate, co-leader of the OSUCCC—James Molecular Carcinogenesis and Chemoprevention Program, said in a statement.

Cruz-Monserrate says reducing risk for pancreatic cancer could start with maintaining a healthy weight. According to the National Institute of Diabetes and Digestive and Kidney Diseases, one in three Americans is overweight, and more than two in five live with obesity. Obesity alone increases a person’s lifetime risk for pancreatic cancer by 20%.

On the flip side, the American Cancer Society estimates that just 10% of pancreatic cancers are linked to heredity risk (genetic markers passed down through families), including the BRCA genes, Lynch syndrome, and others.

“You can’t change your genes, but you can change your lifestyle. For most people obesity is within someone’s power to change. It also increases a person’s risk for type 2 diabetes, other cancers and cardiovascular disease,” said Cruz-Monserrate.

More than 66,000 Americans will be diagnosed with pancreatic cancer in 2024, with less than 13% reaching five-years of survival, according to ACS estimates.

Other modifiable lifestyle factors believed to reduce your lifetime risk for pancreatic cancer include limiting or eliminating alcohol consumption, regular moderate exercise, and a plant-based diet with limited red or processed meat.

More than half of survey respondents (54%) knew that genetic testing helps people understand if they should be screened for pancreatic cancer.

OSUCCC—James researchers are conducting studies to identify ways to screen for early signs of pancreatic cancer, including minimally invasive ways of screening pancreatic cysts, and understanding the roles of diabetes and chronic pancreatitis in pancreatic cancer risk. Until science provides more answers, however, Cruz-Monserrate says taking action to change lifestyle factors—especially maintaining a healthy weight—and understanding your family history are key for risk reduction.

“This disease is too often a silent killer, with no symptoms until it has progressed to less treatable stages. We must continue to aggressively pursue research that will help us prevent, diagnose and treat this disease more effectively,” said Cruz-Monserrate, who is conducting research on the prevention of obesity-related pancreatic cancer and on the impact of exercise on the development of this disease and pancreatitis.

For localized prostate cancer, multimodal artificial intelligence models have revealed a more accurate way to assess prostate cancer risk. 

By combining advanced artificial intelligence with digital pathology images and clinical data, researchers developed a way to approach risk classification that outperforms traditional methods.

These findings were published in JCO Precision Oncology.

The research found that the MMAI risk classification system reclassified 42% of patients compared with NCCN risk groups, accurately identifying more patients as low-risk and fewer as high-risk.

Key implications:

• Reduced overtreatment: This new AI-powered system can identify more patients as low-risk, preventing unnecessary and potentially harmful treatments.
• Improved patient outcomes: By accurately assessing risk, doctors can tailor treatment plans to each patient’s specific needs, leading to better outcomes and fewer side effects.
• Enhanced precision medicine: This technology represents a significant step forward in precision medicine, allowing for more personalized and effective cancer care.

An international, multidisciplinary team of leading neuro-oncology researchers and clinicians has released new recommendations for good clinical practice—a set of guidelines that helps ensure clinical trial results are reliable, and patients are protected—regarding the use of artificial intelligence methods to more accurately diagnose, monitor, and treat brain cancer patients.

The team recently published two companion policy reviews in The Lancet Oncology, on behalf of the clinically authoritative Response Assessment in Neuro-Oncology cooperative group, which is a collaboration of international experts who develop standardized criteria for evaluating treatment response in clinical trials for brain cancer.

Indiana University School of Medicine’s Spyridon Bakas is the lead author on the second policy review, which establishes guidelines for standardization, validation, and good clinical practice of AI for neuro-oncology. He said the new recommendations are a much-needed update to the current standard of care in which individual radiologists measure tumor size, which dictates treatment options. This is not ideal, Bakas said, because the assessment is often subjective. Each radiologist can interpret imaging scans differently, leading to treatment strategies that fluctuate based on who views the scan.

“We can use AI to look at images of the tumors more objectively,” Bakas, the Joshua Edwards Associate Professor in Pathology and Laboratory Medicine and the director of the Division of Computational Pathology at the IU School of Medicine, said in a statement. “AI programs can help determine quickly what type of disease it is, what subtype of tumor and what particular grade it is, in addition to helping track the progress of a lesion during treatment.”

According to the team, there are predictive, prognostic, and diagnostic AI models and solutions that are becoming available for healthcare practitioners, but how they are used varies widely at different institutions.

“Thanks to new technology, there are ways to use AI to help assess whether a tumor is progressing or is stable,” Raymond Y. Huang, associate professor at Harvard Medical School and neuroradiology division chief at Brigham and Women’s Hospital, said in a statement. “However, there needs to be a standardized way to use AI to accurately diagnose and treat patients.”

The team reviewed existing research articles and publications related to current advancements of AI in the field to develop the guidelines, which were presented at this year’s American Society of Clinical Oncology meeting in Chicago, Illinois, and the annual meeting of the European Association for Neuro-Oncology in Glasgow, Scotland. The guidelines will also be presented at the Society for Neuro-Oncology meeting in November in Houston, Texas.

Some of the authors’ guidelines include:

• Using software that has been developed using large and importantly diverse cohorts of patient data.
• Ensuring the AI models for defining a tumor follow World Health Organization criteria.
• Considering how the tumor images are obtained, processed and segmented before analyzing them.

“These guidelines are critical for ensuring that AI tools developed in the U.K. and beyond meet rigorous standards and improve patient outcomes,” Thomas Booth, a co-author from King’s College London, said in a statement. “With these recommendations, we can move towards more accurate, standardized AI applications that benefit both clinicians and patients across the U.K. and internationally.”

Because AI is still new, these recommendations are among the first in the world regarding its proper use in cancer care. However, further study is necessary.

“It is important that we continue our study of these AI models on large, diverse patient populations to continue extending our understanding of disease and improving the way we use them,” Bakas said.

New preclinical data for PHST001, an anti-CD24 antibody drug candidate that is designed to block a key macrophage “don’t eat me” signal on cancer cells, were presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer. The meeting is taking place both virtually and at the George R. Brown Convention Center in Houston from Nov. 8-10, 2024.

PHST001 is sponsored by Pheast Therapeutics.

The presented data show that PHST001, through potent CD24 binding, promotes macrophage-induced phagocytosis in a number of cancer cells and significantly shrinks tumors in vivo. In addition, PHST001 has a favorable PK profile in non-human primates and does not induce immune-mediated toxicity in vitro.

“These data build on the results we presented earlier this year at PEGS showing that PHST001 can powerfully induce an anti-cancer immune response and drive therapeutic efficacy in challenging mouse model systems,” Roy Maute, co-founder and CEO at Pheast Therapeutics, said in a statement. “Macrophage checkpoint therapies such as PHST001 have the potential to expand clinical options for patients in high unmet need oncology indications where other immunotherapies have not yet been successful.”

CD24 is highly expressed by many human cancers, including ovarian and triple negative breast cancer, and high expression of CD24 is a negative prognostic factor in multiple cancer indications. CD24 interacts with the macrophage receptor Siglec-10, and shields cancer cells from attack by macrophages. Pheast has engineered PHST001 to bind CD24 on the surface of cancer cells with high affinity and specificity and to block Siglec-10 binding. 

“The preclinical data demonstrate the potential of PHST001 to address multiple cancer types, and its differentiation as a novel macrophage checkpoint inhibitor with potent inhibition of CD24,” Suzana Kahn, senior director of biology at Pheast Therapeutics, said in a statement. “PHST001 does not have a toxic preclinical profile, which, combined with its superior efficacy in our preclinical models, supports the initiation of first-in-human clinical trials.”

Kahn presented these data in a poster presentation entitled, “PHST001, a humanized anti-CD24 antibody, induces phagocytosis of human tumor cells in vitro and tumor clearance in vivo.”

Scientists at the Johns Hopkins Kimmel Cancer Center have identified 16 genes that breast cancer cells use to survive in the bloodstream after they’ve escaped the low-oxygen regions of a tumor. 

Each is a potential therapeutic target to stop cancer recurrence, and one—MUC1—is already in clinical trials.

The research was published online Sept. 28 in the journal Nature Communications.

Deep in a tumor, full of rapidly dividing cells, cancer cells are faced with a lack of oxygen, a condition called hypoxia. Cancer cells that survive these tough environments end up seeking what they missed, slowly making their way to the oxygen-rich bloodstream and often seeding metastasis elsewhere in the body, said lead study author Daniele Gilkes, an assistant professor of oncology at Johns Hopkins.

The team identified 16 genes responsible for this protection from reactive oxygen species, “which is a stress that occurs when the cells enter the bloodstream,” Gilkes said in a statement. 

“Although the hypoxic cells are localized in what we call the perinecrotic region of a tumor—meaning they’re sitting right next to dead cells—we think that they’re able to migrate into higher [oxygen] levels where they can actually find the bloodstream,” she said. “Cells able to survive super-low oxygen concentrations do a better job of surviving in the bloodstream. This is how, even after a tumor is removed, we sometimes find that cancer cells have set up elsewhere in the body. Lower levels of oxygen in a tumor correlate with worse prognosis.”

The scientists sought to learn what helps these post-hypoxic cells survive in an environment that would kill other cancer cells, and which genes were being turned on to facilitate survival.

In laboratory studies, Gilkes’s team color-coded hypoxic cells green, then applied a technique called spatial transcriptomics to identify which genes were turned on in the perinecrotic region, and that stayed on when the cells migrated to more oxygenated tumor regions. 

They compared cells in the primary tumors of mice with those that had entered the blood stream or the lungs. A subset of hypoxia-induced genes continued to be expressed long after cancer cells escaped the initial tumor.

“The results suggest the potential for a sort of memory of exposure to hypoxic conditions,” said Gilkes.

The new research showed a disparity between what occurs in laboratory models and what happens in the human body, solving a mystery that was puzzling scientists. 

When cells in a dish are hypoxic and returned to high levels of oxygen in a short time, they tend to stop expressing the (hypoxia-induced) genes and go back to normal. However, in tumors, hypoxia can be more of a chronic condition, not acute. 

When Gilkes’s team exposed cells to hypoxia for a longer period—five days was usually enough—they mimicked what was happening in the mouse models.

Results were particularly predictive for triple-negative breast cancer, which has a high rate of recurrence. The researchers found that patient biopsies from TNBC that had recurred within three years had higher levels of a protein called MUC1.

As part of their research model, Gilkes and team blocked MUC1 using a compound called GO-203 to see if it would reduce the spread of breast cancer cells to the lung. Their aim was to specifically eliminate aggressive, post-hypoxic metastatic cells.

“If we reduced the level of MUC1 in these hypoxic cells, they were no longer able to survive in the bloodstream or in presence of reactive oxygen species, and they formed fewer metastases in mice,” said Gilkes. 

However, there are other factors at play, she said, and additional research will be needed to see if this finding is true across cancer types.

A phase I/II clinical trial targeting MUC1 for patients with advanced cancers across a variety of solid tumor types—including those found in breast, ovarian, and colorectal cancer is ongoing, Gilkes said.

Research from the Icahn School of Medicine at Mount Sinai provides new insights into acute myeloid leukemia and its resistance to a common treatment. 

The study, published Oct. 30 in Nature, was led by Eirini Papapetrou, professor of oncological sciences at Icahn Mount Sinai.

Acute myeloid leukemia is a devastating blood cancer that starts in the bone marrow, where blood cells are born. Although AML is a rare disease, approximately 20,800 people will be diagnosed with AML in 2024 in the United States, according to the American Cancer Society.

In this study, researchers found that certain genetic changes, known as RAS mutations, can make leukemia stem cells resistant to drugs. The RAS gene family includes KRAS, HRAS, and NRAS, which encode proteins that control cell signaling, growth, and death. Mutations in these genes typically appear later in the disease and specifically target certain blood cell types, making them more aggressive and harder to treat, the researchers found.

“We discovered that these RAS-mutant leukemia stem cells behave differently from other leukemia stem cells,” Papapetrou said in a statement. “This could explain why some patients do not respond well to the widely used drug venetoclax, which the Food and Drug Administration approved for AML treatment in October 2020.”

This study used innovative genetically engineered models and patient-derived cells, combined with advanced genomic technologies, to investigate the role of RAS mutations in leukemia and their impact on drug response. 

The researchers discovered that RAS mutations specifically target granulocyte-monocyte progenitors that have already acquired early mutations, transforming them into RAS-mutant leukemia stem cells. 

This leads to leukemias with distinct characteristics, including resistance to venetoclax. This resistance is caused by changes in proteins that control apoptosis, a form of cell death, impacted by RAS mutations.

“This study has implications for patients with RAS mutations,” Papapetrou said. “It suggests that treatment with venetoclax might not be effective for these individuals and could even worsen their condition. For these patients, providers should consider a combination of therapies that include new RAS inhibitors, which could improve treatment results.”

The findings highlight the importance of personalized medicine, where treatments are tailored to the specific genetic characteristics of each patient’s cancer. 

This approach could lead to better outcomes and improved quality of life for those battling leukemia.

“Our study supports the rationale of testing combinations of venetoclax with RAS inhibitors, as well as MCL-1 and/or BCL-xL inhibitors,” Papapetrou said. “Such inhibitors are currently at different stages of preclinical and clinical development and, based on our results, could be tested in combination with venetoclax in patients with AML with RAS mutations.”