From Genghis Khan's Tomb To The Hanging Gardens Of Babylon — 9 Important Archaeological Sites That Still Haven't Been Discovered
Through the centuries, historical sites are bound to disappear. Whether due to climate change, political turmoil, or even grave robbers, there are many reasons why discoveries at notable locations are sparse, but there are still typically traces of the people and customs. Occasionally, though, it's as if they never existed to begin with...
One might believe that, in regard to important historical figures and locations, there would be some form of record, whether written or oral, that would allude to a location. However, that's not always the case...From the Hanging Gardens of Babylon to Cleopatra's tomb, here are 9 important archaeological sites that may never be found:
1.The Hanging Gardens of Babylon:
Considered one of the "Seven Wonders of the Ancient World," the Hanging Gardens of Babylon are the only Wonder that has remained elusive to archaeologists.
Most historians believe that in the sixth century BCE, King Nebuchadnezzar II had the Gardens constructed as a gift for his wife, Amytis, who was homesick for her native Media (modern-day Iran). In that day and age, it would have taken a feat of engineering to ensure the gardens were properly irrigated, leading scientists to theorize that a system akin to Roman aqueducts would have delivered water from the nearby Euphrates River to the Gardens.
While there are many descriptions of the Gardens in Greek and Roman texts, these were second-hand accounts that had been passed down throughout the centuries, as there is no mention of them in any preserved Babylonian texts. Due to the lack of archaeological evidence, some scientists assume the Gardens never truly existed. However, Oxford's Dr. Stephanie Dalley, an Assyriologist, discredited those assumptions: "That's a pretty stupid copout, really. It doesn't make sense to say we couldn't find it, so it didn't exist."
Dalley claims the lack of archaeological evidence is due, rather, to the fact that the Gardens weren't located in Babylon at all, but rather in Nineveh, the capital city of Assyria (modern-day Iraq and Turkey). She believes Assyrian king Sennacherib, not Nebuchadnezzar II, built the Gardens in the seventh century BCE, an entire century earlier than hypothesized in Babylon.
After combing through ancient texts, she noted that Sennacherib described an "unrivaled palace" in his kingdom and a "wonder for all peoples," as well as a bronze water-raising screw, which could have been used to irrigate the Gardens. Dalley explained that confusion over their location might have stemmed from the fact that after Assyria conquered Babylon in 689 BCE, Nineveh was renamed "New Babylon."
Excavations near Nineveh (near modern-day Mosul) uncovered a complex aqueduct-esque system with the inscription: "Sennacherib, king of the world…Over a great distance, I had a watercourse directed to the environs of Nineveh."
It's still unknown who or what destroyed the Gardens. Strabo's writings described "Gardens" that were in ruins by the end of the first century BCE and claimed that Alexander the Great wanted to repair them. However, the Macedonian king died before he could complete his mission, and "none of the persons who succeeded [Alexander] attended to this undertaking."
2.Genghis Khan's tomb:
Before Genghis Khan died in August 1227 CE, he requested that his grave not be marked in any way. However, this hasn't stopped a variety of individuals, from archaeologists to grave robbers, from attempting to find the ruler's final resting place, despite the fact that Marco Polo recounted that even by the late 13th century, the mystery eluded even the Mongols themselves.
Most fieldwork that has taken place to find Khan's tomb has centered around Burkhan Khaldun in northeastern Mongolia, near his birthplace. The location was even mentioned in The Secret History of the Mongols, the oldest surviving work about Khan's final days. According to the text, he declared it to be the most sacred mountain in Mongolia and said, "Bury me here when I pass away." (Historians still don't know what officially caused his demise, but one popular theory is that it was due to injuries sustained from falling off a horse in 1226). Despite this statement, archaeological searches in the area have been fruitless.
The details of Khan's burial have long been shrouded in mystery. In an oft-recounted tale, Marco Polo claimed that after 2,000 slaves finished burying Khan, they were killed by soldiers, who were in turn killed by another group of soldiers, who later killed themselves in an effort to finally secure the privacy of their revered ruler's burial site. However, this legend is not mentioned in contemporary stories.
There have also been long-standing rumors of a curse surrounding Khan's grave. In 2002 this theory recirculated after an American expedition, led by University of Chicago historian, John Woods, and former gold trader, Maury Kravitz, abruptly ended after a series of "mishaps," including workers being bitten by pit vipers (it is rumored that a two mile long wall of snakes protects the warlord's final resting place) and vehicles inexplicably rolling down hillsides.
If this didn't deter the mission, the final blow was when Mongolia's prime minister accused the team of desecrating a sacred site, stating: "I regret that our ancestors' golden tomb has been disturbed and the purity of our burial places tainted for a few dollars. This place should remain pure for the souls after death." Despite the team's theory that Khan's tomb was indeed close to their search area, Kravitz told reporters, "In each of the countries and cities and sovereign states he conquered, Genghis Khan brought back the wealth of that culture on two-wheeled wagons. Not one thing has been found. Not a single bejewelled dagger. Not a single necklace. It all went into Mongolia and never exited. (Some believe Khan's tomb contains vast quantities of treasure)."
After that trek ceased in 2002, Khan's palace was discovered by a Japanese-Mongolian expedition in October 2004, 150 miles east of Ulan Bator, which led to academic excitement that his burial site might be situated nearby. Despite this promising theory, nothing was found. There have been other expeditions since that time, but no major breakthroughs have occurred.
3.The Lost Colony of Roanoke:
One of the biggest mysteries of pre-colonial America is the fate of the Lost Colony of Roanoke. While we do know that the colony was located on present-day Roanoke Island off the coast of North Carolina, archaeologists are still unable to pinpoint the settlement's exact location and where/if the colonists resettled elsewhere. In the words of Adrian Masters, a University of Texas historian, "It's the 'Area 51' of colonial history."
The story of the Lost Colony began in 1584 when Sir Walter Raleigh sought permission from Queen Elizabeth I to establish a permanent North American settlement. She approved his request and granted permission for the establishment of "Virginia." Shortly after, over 100 British men, women, and children boarded the ship Lyon, and ten weeks later, landed on the coast of North Carolina.
Roanoke Island was only meant to be a stopping point in the settlers' journey, as records show they intended to move 50 miles into the mainland, eventually making their home in Salmon Creek. But winter derailed their plans, forcing them to settle in Roanoke for longer than intended. The changing seasons, as well as a tenuous relationship with the local Algonquian tribe, the colony's governor John White to return to England to gather supplies. On August 25, 1587, the settlers asked, "...we all of one mind, and consent, have most earnestly entreated, and incessantly requested John White, Governor of the planters in Virginia, to pass into England, for the better and more assured help..." White was reluctant, but realized supplies would be beneficial, so on August 27, he set off for his home country.
His return trip was particularly ill-timed as it took place in the midst of the war between Spain and England. The threat of the fearsome Spanish Armada caused Elizabeth I to prohibit British ships from leaving the port, lest they be needed to face off against the Spaniards. In April 1588, despite the prohibition, White was able to arrange a relief mission. However, a battle with the French forced the ships to return to England.
White was unable to arrange another voyage until 1590, this time with four ships owned by privateers, who agreed to drop him off at the colony. On August 18, 1590, he landed in Roanoke and discovered the settlers had vanished without a trace, leaving behind only the word "Croatan" carved into a wooden post.
Croatan was the name of a nearby island that was home to a Native American tribe of the same name. Hypotheses about the fate of the settlers have ranged from kidnapping or possible assimilation into a tribe to a pandemic. But, nearly five centuries later, these theories are still unproven.
In recent decades, archaeological excavations have turned up few clues as to what took place in White's absence. Many researchers and archaeologists now believe that surviving settlers broke off into smaller groups and migrated to different areas. In 2020, the First Colony Foundation stated that "compelling evidence" had been found that a "satellite site" had been established along Salmon Creek for a period of time, as both excavations and ground-penetrating radar revealed ceramic artifacts that were later identified as being from the Elizabethan period.
The Foundation has also planned an excavation near Fort Raleigh National Historic Site in Manteo, North Carolina, in the hopes of finding the original settlement.
4.Ankhesenamun's (Nefertiti's daughter and King Tut's wife) tomb:
Despite her half-brother/husband, King Tut's final resting place being discovered in 1922, over a century later, the tomb of Ankhesenamun has yet to be uncovered.
Ankhesenamun, Nefertiti's daughter, was married to the "Boy King" when she was 13 years old. The couple had two daughters before Tut died around the age of 18 for causes that are still unknown. Ankhesenamun was featured prominently in the artwork within his tomb, including one scene that shows her assuming the role of priest during his coronation and again on the back of his golden throne.
After Tut's death, not much is known about her life, except for the fact that she initially refused to marry Ay, Tut's successor (and perhaps her grandfather). Instead, asking Suppiluliuma I, a Hittite king, to send one of his sons to marry her and therefore become pharaoh. This request confused the king, but he proceeded to send his son Zannanza, who was killed on the Egyptian border by General Horemheb (who later became pharaoh himself). A ring bearing the name of both Ankhesenamun and Ay seems to suggest that she eventually married him, but evidence supporting this theory has been inconclusive. Some also theorize that she may have been executed after communicating with the Hittites.
Despite her esteemed rank, Ankhesenamun's request to the Hittite king was the final time she was mentioned in the historical record, and her burial site has been lost to the sands of time. In 2016, archaeologists who scanned Tut's tomb believed they had found undiscovered chambers, which could possibly have led to Nefertiti or even Ankhesenamun's tombs. However, a later scan by National Geographic disproved this theory.
In 2017, Owen Jarus of LiveScience reported that archaeologists believed they had found Ankhesenamun's final resting place in the Valley of the Monkeys, which was adjacent to the Valley of the Kings. However, the dig's leader, Zahi Hawass, released a statement, claiming that they were not certain if a tomb existed at all and if it did, whether or not it belonged to Ankhesenamun.
As of 2025, nothing relating to Ankhesenamun's final resting place has been discovered.
5.The Ark of the Convenant:
Despite what one might believe after watching Raiders of the Lost Ark, the Ark of the Covenant has yet to be discovered. Throughout the centuries, individuals have searched for the Biblical artifact to no avail.
According to the Book of Exodus, during Moses' 40-day stay on Mount Sinai, God commanded him to have the Ark of the Covenant built and showed him a blueprint for a tabernacle for the Ark as well as furnishings it should contain. Constructed by Bezalel and Oholiab, the Ark itself was described as being made of acacia wood and overlaid with pure gold, with a crown of gold around it, and fitted with staves (vertical planks) overlaid with gold, so that it could be safely carried (in the books of Samuel and Chronicles, it is written that after a cart carrying the Ark tilted, a man named Uzzah reached out to steady it with his hand, which violated divine law, and was thereby killed by God for his error), and decorated with cherubims. The Ark was also designed to contain the original stone tablets on which the Ten Commandments were written.
The Ark was later lost to the Philistines (a group who had settled in Canaan) for seven months. However, after mishaps began plaguing the Philistines, they returned the Ark to the Israelites. Despite the significance of this artifact, it was last seen in Jerusalem within the Temple circa 586 BCE when the Babylonian Empire conquered the Israelites. To this day, historians are unsure if it was stolen, destroyed, or hidden.
Many believe the Ark made its way to Ethiopia. According to Ethiopian tradition, it was preserved in the Church of Mary of Zion in Aksum, an ancient holy city. Some even claim that Emperor Iyasu viewed and spoke to the artifact in 1691. Now, it supposedly resides in the Chapel of the Tablet, where it was moved during Haile Selassie's reign, and is guarded by a singular monk, who recites the Book of Psalms and burns incense before it. However, the church's authorities have never allowed the artifact to be studied for authenticity.
Another theory is that the Ark was hidden within a network of passages built underneath the First Temple in Jerusalem before the Babylonians destroyed it. However, this hypothesis cannot be tested because the site of the First Temple is now the Dome of the Rock shrine, which is sacred in Islam. Therefore, it cannot be excavated.
There are many, many theories about the Ark's current whereabouts. However, it seems unlikely we'll ever know what truly occurred, as archaeologist Fred Hiebert explained to National Geographic, "Even if such an object were discovered, how would one test its Biblical authenticity against that of other ancient artifacts? We are talking about things [at] the crossroads between myth and reality. I think it's great to have stories like [that of] the Ark of the Covenant. But I do not believe, as a field archaeologist, that we can use the scientific method to prove or disprove [them]."
6.Treasures of the Second Temple:
While we're on the topic of missing Biblical artifacts, it goes without saying that one of the biggest archaeological mysteries is the whereabouts of the treasures of the Second Temple.
After the Babylonians plundered the First Temple during their conquest of Jerusalem in 597 BCE, it was noted in the Book of Ezra that most of the stolen items were restored to the Israelites. However, over six centuries later, when the Roman emperor Titus laid siege to Jerusalem in 70 CE, the recovered treasures and many others sacred items (including the Golden Menorah, the Table of Showbread, and the golden altar of incense) that had been gathered over the centuries, vanished from the Second Temple.
When the Arch of Titus was constructed a few years later, the commemorative monument showed the Romans carrying their plundered treasures through the streets of their homeland. It was noted that some of these items were stored in the Roman Temple of Peace, where the Golden Menorah was displayed for centuries.
A little over three centuries later, the Romans were subjected to three days of looting and pillaging by the Visigoths, after which historian Procopius wrote that the invader's spoils contained, "the treasures of Solomon's Temple, a sight most worthy to be seen, articles adorned with emeralds, taken from Jerusalem by the Romans." The Visigoths resettled in the southern region of France, where some believe the pillaged treasures may still lie.
However, another theory states that the Visigoths were not so lucky as to keep their treasures. Many claim the items wound up in the possession of Byzantine Emperor Justinian, who believed them to be cursed and ordered their redistribution to churches in Jerusalem.
After the items were returned to their native land, some believe they were once again seized by either Persian or Muslim invaders and melted down. Others theorize they found their final home inside the mysterious Vatican vaults. However, in 2004, the Israel Antiquities Authority was granted permission to explore the vaults and found no sign of the items.
7.The Akkadian capital of Agade:
In 2334 BCE, Sargon the Great united all of Mesopotamia and developed the world's first multi-national political dynasty, the Akkadian Empire, which would serve as an example to all future Mesopotamian civilizations. At the height of its power, the Empire encompassed a large section of modern-day Iraq and Syria. Its people were known for pioneering innovations such as the world's first postal system and cuneiform writing. Akkadia was also recognized for Sargon's institution of Ishtar, the Semitic goddess of war, who served as the entire dynasty's deity, rather than just a single city.
This is what brings us to the lost city of Agade. Agade (also referred to as Akkade), Akkadia's capital, served as the Eulmash temple, which was devoted to Ishtar. However, when the Akkadian Empire fell around 2154 BCE, Agade had become largely abandoned. Later Mesopotamian rulers still revered the history of the empire, as Benjamin Foster, an Assyriologist, explained, "Their relics were admired, their inscriptions were studied, and their historical memory was kept alive for two thousand years."
Despite Agade's abandonment, the location of its ruins was still known in the 6th century BCE, as Babylonian king Nabonidus claimed to have excavated the site, writing, "I relaid the foundation, the altar, and dais, along with two ziggurats, and made firm its brickwork. I built them up to ground level so that the foundation of Eulmash shall never again be forgotten." Sadly, as is the case with many ancient sites, the location of the Eulmash temple and Agade itself had been mostly forgotten until the mid-1800s.
During the archaeology boom of the 19th and 20th centuries, Assyriologists once again took interest in ancient Mesopotamian culture and recognized Agade as a city of great cultural importance.
Historians today seem to agree that Agade was situated along the banks of the Tigris River, most likely between the modern cities of Baghdad and Samarra. However, due to the Tigris River changing course throughout the millennia, there is concern that Agade might have simply been washed away.
As Nele Ziegler, an Assyriologist for the French National Center for Scientific Research, explained, "We don't have many clues to where it is. There's no text that tells you, for instance, how much time it took to go from Sippar to Agade." She continued, "We'd really like to find it. There was a cultural revolution going on when the Akkadians came to power. It would be really interesting to see what they imagined as their ideal capital city." As of now, the city still remains lost.
8.The Heirloom Seal of the Realm:
In 221 BCE, the Heirloom Seal of the Realm (aka the Imperial Seal of China) was allegedly carved out of a sacred piece of jade, known as the Heshibi, under the orders of Qin Shi Huang, the first emperor of China, after he united the nation and destroyed the remaining Warring States.
When China's second emperor, known as Ying Huhai, died, the seal was gifted to the Han dynasty's new emperor, thereby becoming known as the "Han Heirloom Seal of the Realm." Years later, the sole emperor of the Xin dynasty forced the Han empress dowager to hand over the Seal. The Seal survived this and many more centuries of political turmoil; in all, it was passed through six dynasties before becoming "lost" during the Five Dynasties and Ten Kingdoms period, which lasted from 907 to 960 CE. While it is not known what specifically happened to the Seal, there are three prominent theories that allude to its disappearance, with one of the most prominent being that Yuan emperors acquired it.
However, that theory is slightly discredited after one learns that when Ming armies captured the Yuan capital in 1369, they gained ownership of only one out of the emperor's eleven seals. When Ming armies invaded again the following year, the Seal was still missing. Once the Ming dynasty began, the Seal was officially considered lost, and over six and a half centuries later, it still is.
Several ancient seals have been discovered in the Chinese countryside in recent decades, which have drawn many excited hypotheses that they could have been the long-lost Heirloom Seal. However, these theories have been disproven.
9.Cleopatra's tomb:
On August 10 (or possibly 12), 30 BCE, after Egyptian forces were crushed by the Roman army in the Battle of Actium, Cleopatra killed herself. Despite it being over two millennia since the queen was found lying, lifeless, on her golden couch, we still do not know where her final resting place is. According to ancient historians, Octavian, the Roman ruler, allowed Cleopatra and her husband, Mark Antony, who had killed himself nine days prior, to be buried together.
In his writings, Plutarch stated that Cleopatra's tomb was located near a Temple of Isis (the Egyptian goddess of healing and magic), as both he and fellow historian Cassius Dio noted that in her final days, she had frequently traveled from her palace to the tomb. Dio further supported the claim that she and Antony "were both embalmed in the same fashion and buried in the same tomb."
In 2004, Kathleen Martínez, a lawyer-turned-archaeologist, began searching for the tomb. After studying Ancient Roman texts, Martínez investigated 21 temple sites she believed could house Cleopatra's remains, leading her to primarily focus on Taposiris Magna, a ruined temple which lies 25 miles west of Alexandria.
She told National Geographic, "What brought me to the conclusion that Taposiris Magna was a possible place for Cleopatra's hidden tomb was the idea that her death was a ritual act of deep religious significance carried out in a very strict, spiritualized ceremony. Cleopatra…wanted to be buried with [Antony] because she wanted to reenact the legend of Isis and Osiris. The true meaning of the cult of Osiris is that it grants immortality. After their deaths, the gods would allow Cleopatra to live with Antony in another form of existence, so they would have eternal life together."
In December 2024, her team discovered a small marble bust that the Egyptian Ministry of Tourism and Antiquities claimed Martinez told them might bear the resemblance of Cleopatra, however, in the press release, the Ministry noted that other archaeologists disagreed with her theory, claiming the "facial features differ from known depictions of Cleopatra VII. It is more likely the statue represents another royal woman or princess."
Despite some impressive findings, Martinez and her team have yet to locate Cleopatra's final resting place. Zahi Hawass, an early supporter of Martinez's work and the former secretary-general of the Supreme Council of Antiquities, told Live Science, "There is no evidence at all that Cleopatra's tomb could be in [Taposiris Magna]. I believe now that Cleopatra was buried in her tomb that she built next to her palace and it is under the water. Her tomb will never be found."
Did any of these "lost" historical sites surprise you? Can you think of any other important historical locations that haven't been discovered? Let us know in the comments!

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In recent decades, scientists have approached the problem from another angle: experiments in cells and animals. These have revealed important mechanisms by which stress can alter tumors, says Julienne Bower, a health psychologist at UCLA who coauthored a 2023 article on the connection between the brain and the immune system in diseases, including cancer, in the Annual Review of Clinical Psychology. Such studies are showing that "psychological factors can influence aspects of actual tumor biology," she says. On the flip side, studies in people and animals suggest that blocking the chemical signals of stress may improve cancer outcomes. Today, a growing number of researchers think that psychological factors can influence cancer's progression once someone has the disease. "I don't think anyone appreciated the magnitude by which even mild stress, if it's chronic, can have such a negative influence on cancer growth," says Elizabeth Repasky, a cancer immunologist at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. New interest in the relationship between stress and cancer growth emerged in part from research into how stress affects the body's response to human immunodeficiency virus (HIV). In the 1990s and early 2000s, genomics researcher Steve Cole and his team at UCLA investigated why people infected with HIV who were under high stress tended to have worse outcomes, including larger viral loads and poorer responses to antiretroviral drugs. Cole's team discovered several routes through which stress could worsen HIV infections. In monkeys, they found, the lymph nodes of stressed animals had many more connections to sympathetic nerve cell fibers—which execute the body's fight-or-flight response—than the nodes of unstressed monkeys. Lymph nodes contain immune cells, and the nerve fibers reduced the antiviral function of these cells, which, in turn, led to an increase in the replication of a version of HIV that infects monkeys and apes. Lymph nodes, in addition to housing immune cells, also act as the body's drainage system, flushing away toxins through a network of tissues, organs and nodes called the lymphatic system. Importantly, cancer cells can hijack this system, using it to travel through the body. Erica Sloan, a postdoctoral trainee of Cole who was involved in the HIV work, wondered whether stress, via the sympathetic nervous system, might also affect lymph nodes in those with cancer. Sloan, now a cancer researcher at Monash University in Australia, went on to discover in mice that chronic stress increases the number of connections between the lymphatic system and breast tumors, making the cancer cells more likely to spread. Strikingly, treatment with a drug—a beta blocker that blunts the activity of key molecules of the sympathetic nervous system such as norepinephrine—prevented these effects. Research by other groups has shown that stress can lead to molecular changes, particularly within the immune system, that influence how cancer progresses. Some of this work suggests that, when stress leads to inflammation—a broad immune reaction typically brought on by injuries and infections—it can boost the growth of tumors. Stress can also impair the activity of immune cells that play an active role in fighting cancer. In the early 2000s, research by University of Iowa behavioral scientist Susan Lutgendorf and her colleagues found that in patients with ovarian cancer, depression and anxiety were associated with impaired tumor-fighting immune cells. In another study of people with ovarian cancer, the researchers found that poor social support was linked to higher levels of a growth factor that stimulates blood vessel growth around tumors. This growth, called angiogenesis, enables new blood vessels to supply nutrients to tumors and—like the lymphatic system—provide pathways through which cancer cells can spread to other parts of the body. Lutgendorf and her colleagues have since found that stressful situations have a similar effect on mice with ovarian cancer, enhancing tumor angiogenesis and cancer spread. Equally important, they've found that these effects can be reversed with beta blockers. Other groups have found similar effects of blocking stress signals on other types of cancer in rodents, including blood and prostate cancer. In addition, researchers have found that increasing levels of stress hormones such as norepinephrine and cortisol in mice can make previously dormant cancer cells more likely to divide and form new tumors. Studies like these are revealing that stress can trigger a cascade of biochemical changes and alter a cancer cell's environment in a way that may promote its spread. "Stress signaling and stress biology really have an impact on most—if not all—of these processes," says Jennifer Knight, a cancer psychiatrist at the Medical College of Wisconsin. If stress can make cancer worse, how can the process be stopped? Little by little, new treatments are emerging. For about half a century, clinicians have used beta blockers to treat hypertension. By scouring data from patient registries, researchers found that people with cancer who already had been taking certain kinds of beta blockers at the time of diagnosis often had better outcomes, including longer survival times, than those who were not on the medicines. Over the past few years, several clinical trials—most of which are small and early-stage—have directly tested whether beta blockers could benefit people with cancer. In one pair of studies, a research team led by neuroscientist Shamgar Ben-Eliyahu at Tel Aviv University, administered the beta blocker propranolol along with an anti-inflammatory drug to people with colorectal or breast cancer five days before surgery. The team chose this timing because earlier research had shown that while surgery is an opportunity to remove the tumor, it can also paradoxically provide the chance for the cancer to spread. So blocking any potential effects of stress on cancer spread, they reasoned, could be crucial to a patient's long-term prognosis. These trials, which involved dozens of patients, revealed that the tumor cells of those who received the drugs showed fewer molecular signs of being able to spread—a process known as metastasis—less inflammation, and an increase in some tumor-fighting immune cells. For colorectal cancer patients, there were also hints that the intervention could reduce cancer recurrence: Three years after the procedure, cancer returned in two of the 16 patients who received the drugs, compared to six of 18 patients who didn't receive those meds. Other studies have assessed the effect of using beta blockers alone, without anti-inflammatory drugs. In 2020, Sloan and her colleagues published a study including 60 breast cancer patients, half of whom were randomly assigned to receive propranolol a week before surgery, while the other half received a placebo. They, too, found that tumor cells from patients who received beta blockers had fewer biomarkers of metastasis. Stress-reducing beta blockers may also benefit other cancer treatments. In a 2020 study, Knight and her team looked at the effect of beta blockers in 25 patients with multiple myeloma who were receiving blood stem cell transplants. Patients who took beta blockers had fewer infections and faster blood cell recovery—although the study was too small to properly evaluate clinical outcomes. And in a small study of nine people with metastatic skin cancer, Repasky and her colleagues found hints that beta blockers might boost the effectiveness of cancer immunotherapy treatments. While studies on beta blockers are promising, it's not clear that these drugs will improve outcomes in all kinds of cancers, such as lung cancer and certain subtypes of breast cancer. Some patients can react badly to taking the medications—particularly those with asthma or heart conditions such as bradycardia, in which the heart beats unusually slowly. And, crucially, the drugs only block the endpoint of stress, not its cause, Repasky says. They will therefore likely need to be combined with mindfulness, counseling and other stress-reducing strategies that get closer to the root of the problem. Such interventions are also in the works. Bower and her team have conducted clinical trials of mind-body interventions such as yoga and mindfulness meditation with breast cancer survivors, to improve health and promote lasting remission. They've found that these therapies can decrease inflammatory activity in circulating immune cells, and they speculate that this may help to reduce tumor recurrence. Ultimately, bigger clinical trials are needed to firmly establish the benefits of beta blockers and other stress-reducing interventions on cancer survival outcomes—and determine how long such effects might last. The timing of treatment and the type of cancer being treated may play a role in how well such therapies work, researchers say. But lack of funding has been a barrier to conducting the larger follow-up studies needed to answer such questions. The work isn't yet backed by pharmaceutical companies or other organizations that support large studies in oncology, Knight says. And for now, whether stress can increase a person's risk of developing cancer in the first place, as the ancient Greeks once postulated, remains a mystery. Population studies linking stress to cancer risk are often complicated by other factors, such as smoking, poor nutrition and limited access to health care. "We have no definitive way of saying, 'If you're stressed out, you're going to develop cancer,'" says Patricia Moreno, a clinical psychologist at the University of Miami Miller School of Medicine and coauthor of an article in the 2023 Annual Review of Psychology about stress management interventions in cancer. But for people who already have a cancer diagnosis, many researchers argue that the evidence is strong enough to include stress management in clinical practice. On average, cancer patients do not receive psychological therapies that can reduce stress at the level for which they are needed, says Barbara Andersen, a clinical psychologist at Ohio State University. Although they won't be necessary for every patient, many can benefit from mind-body interventions, she says. "I'm not saying they should be a first priority, but they shouldn't be the last." This story was produced by Knowable Magazine and reviewed and distributed by Stacker.