SAN DIEGO: Dennis Lyon was a genetic train wreck. Cancer was ravaging his liver, lungs, bones and brain, and tests showed so many tumor mutations that drugs targeting one or two wouldn’t do much good. It seemed like very bad news, yet his doctors were encouraged.
The reason: People with the most messed-up genes often are the ones who do best on treatments that enlist the immune system.
“These are the patients we used to be very depressed about,” thinking they couldn’t be helped, said Dr. Razelle Kurzrock at the University of California, San Diego. “Now when we see those types of patients, we’re really excited,” because there are so many ways for the immune system to recognize the cancer cells as abnormal.
Immunotherapy is the hottest thing in cancer care. Drugs called checkpoint inhibitors can vanquish some advanced cancers by removing a chemical cloak that hides them from the immune system. Former President Jimmy Carter got one at age 91 for skin cancer that spread to his brain, and now is in remission.
But they’re expensive, have side effects, and work for only about one-quarter of patients — as few as 5 percent with colon cancer and as many as half with the skin cancer, melanoma. Sometimes the benefits are brief.
Worst of all: For a small number of unlucky folks, treatment can backfire. Their cancer grows exponentially after getting a checkpoint drug.
“We’re going to have to figure out not only who to treat with immunotherapy but who not to treat,” Kurzrock said.
Gene tests are starting to help sort that out. But for patients, the big question is “Will it work for me?“
PREDICTING WHO BENEFITS
The first step is testing for a protein called PD-L1 that’s often involved in forming that chemical cloak. Some checkpoint drugs target this or a related protein, so people with a lot of it should respond to treatment.
That was the hope when Diane Tippett showed up last October at Georgetown Lombardi Comprehensive Cancer Center with a salivary gland cancer that had spread to her liver and lungs.
“Five years ago, I probably would have thrown up my hands and given her standard chemo,” said the center’s director, Dr. Louis Weiner.
Instead, he ordered tests that showed Tippett had a PD-L1 mutation, meaning her cancer made a lot of it. He started the 49-year-old Leonardtown, Maryland, woman on a checkpoint drug, Opdivo, and told her to come back in a few months.
“Quite honestly, I didn’t know if I’d ever see her again,” he said.
Now, Tippett’s lung tumors are gone. Her liver tumor shrank 50 percent and is stable. She got married in July and says she feels great.
“I don’t feel any different than you do. I’m not tired, I’ve got all my hair,” she said. “I want more people to know about it and to ask their doctors about it,” she said of immunotherapy and the testing that led her to it.
NOT THE WHOLE STORY
That protein isn’t a very reliable predictor, though. Some people with a lot of it don’t benefit from the drugs and the opposite also is true. There are other checkpoints besides that one, too.
Researchers increasingly are focusing on something else Tippett had: a high number of flawed genes. It’s a sign that tumors have been evolving over time and are hard to treat with drugs that target a single gene. It sometimes accompanies two other DNA problems that some checkpoint drugs already are approved to treat.
Lyon, the San Diego man, had nearly two dozen different mutations after his skin cancer spread widely. In October 2015, he started on Opdivo and was in near-complete remission within two months. Recent tests showed no active cancer in his spine and lungs, and doctors think small spots in his brain and liver may be scar tissue, though they can’t know for sure. A test for tumor DNA in his blood found none.
“It would appear my cancer is all dead,” he said, and called it “nothing short of miraculous” that gene tests led to successful treatment after years of trial and error. “I’m so grateful. No one’s lucky that gets cancer but I may be in an era where there’s a way through this tunnel.”
Three-quarters of patients who are helped by checkpoint drugs have long-lasting benefits, as Lyon did, said Dr. Steven O’Day, an immunotherapy expert at Providence Saint John’s Health Center in Santa Monica, California.
“When you respond, it’s a home run in terms of long-term survival,” O’Day said. “But we still have to be better at predicting who those patients are.”
THE DARK SIDE
Others have not been so fortunate. In November, French researchers reported that 12 of 131 patients, or 9 percent, got much worse after checkpoint drugs, which seemed to speed their tumor growth.
Kurzrock checked with colleagues and quickly found more cases — a 73-year-old man with bladder cancer, a 65-year-old woman with endometrial cancer, and a 44-year-old breast cancer patient whose tumors “just exploded” in size within two months of immunotherapy.
In a report on 155 patients, she tied several gene mutations to this risk. Kurzrock has consulted for some gene-medicine makers and co-founded a company using a software program to determine best treatments for patients depending on their tumor genes.
The unfortunate cases are a reality check, said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society.
“We are not paying close enough attention to those people” and need to know whether they fared badly because of their treatment or for other reasons, he said.
SHOULD WE BE DOING ‘IMMUNOGRAMS’?
That’s the question Dr. Eric Topol, director of the Scripps Translational Science Institute, posed a gene medicine conference he organized in March at the suburban San Diego research center. Should there be baseline tests to map what patients’ natural defenses look like? For example, how many immune system soldiers called T cells do they have in the area of the tumor?
Max Krummel is working on a roadmap to do that. The University of California, San Francisco, scientist heads a project with $10 million from three companies that make checkpoint drugs. He is analyzing hundreds of tumor samples to see what immune system features spell success or failure.
“We’re not looking at how the immune system changes,” but for what starting point works best with the drugs, he said. “What we’re seeing is that the kinds of cells you have in a tumor predict who’s going to respond.”
Krummel, who was involved in work that led to Yervoy, the first checkpoint drug, has started a company to try to tune up one part of the immune system he thinks is key to maintaining a healthy balance.
Cancer exists because the immune system isn’t working as it should, he said, so successful immunotherapy may require “treating the immune system, not treating the tumor.”
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Marilynn Marchione can be followed on Twitter: @MMarchioneAP
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This Associated Press series was produced in partnership with the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.
The big question: Will cancer immune therapy work for me?
The big question: Will cancer immune therapy work for me?
Where We Are Going Today: ‘UPPER’ – burger spot in Jeddah
- The yellow cheese burger sticks to familiar toppings like iceberg lettuce, grilled onions, and a standard sauce
Located in the Al-Zahra District of Jeddah, UPPER is a burger spot that focuses on a small menu built around quality ingredients and generous portions.
While the menu is limited, the flavors are solid, and the casual setting makes it a decent option for those who enjoy burgers.
The wagyu beef burgers are the main draw. Served on a pretzel bun with either white or yellow cheese, the patties are juicy and well-prepared.
The yellow cheese burger sticks to familiar toppings like iceberg lettuce, grilled onions, and a standard sauce. The white cheese version offers a slightly different mix with baby rocca, onion jam, Dijon pepper sauce, and goat’s cheese.
Chicken options include both crispy and grilled versions. The crispy ones — including zesty and chipotle — come with American cheese and a mildly spicy sauce. The grilled chicken burger is lighter, with Emmental cheese and ranch dressing.
Among the sides, the grilled corn with spiced sour cream sauce stands out, and the fries are crisp and satisfying. Lamb chops are also on the menu, but they feel more like an add-on than a core item.
Desserts like tiramisu and molten chocolate cake are straightforward and familiar.
House-made sauces like the smoky chipotle mayo and zesty lemon sauce add a nice touch. For more, check the location’s Instagram @upper.sa.
Where We Are Going Today: ‘Layali Al Iraq’ in Jeddah
- Layali Al Iraq has an enclosed grilling room where the signature grilled carp (shabout) is cooked upright over a fire
Layali Al Iraq restaurant in Jeddah offers authentic Iraqi cuisine in a traditional setting.
The restaurant’s spacious interiors feature classic Iraqi elements including mashrabiya woodwork, stone walls, murals, and a central fountain. Soft Iraqi music adds to the calm atmosphere.
While browsing the menu, guests are offered complimentary lentil soup, lemon slices, and saj bread — a nice touch.
I tried the tabbouleh, Mosuli-style kibbeh, and a cold mezze platter. The tabbouleh was large — enough for several people — and all the ingredients were fresh and flavorsome.
Layali Al Iraq has an enclosed grilling room where the signature grilled carp (shabout) is cooked upright over a fire. I ordered a 1 kg carp, which arrived nicely crisped and served with fresh vegetables.
The lamb shoulder came with both plain and tomato-based rice, plus pistachio-stuffed kebabs — hearty and well-seasoned.
To finish, traditional Iraqi tea istikanah is served in authentic cups by staff in traditional dress.
Service was quick, and prices are reasonable given the portion sizes. Visit @layali_al.iraq_restaurant on Instagram for more information.
Where We Are Going Today: ‘The Door’ restaurant in Riyadh
- Scallops and an accompanying sauce were also good, and the smoked baba ghanouj was particularly memorable
The Door restaurant in Riyadh has a cozy atmosphere that enhances the overall dining experience for food lovers.
We started with the lemon garlic pasta, which was bursting with flavor. A beef burger, topped with caramelized onion, was delicious, but the large serving may be too much for some. Fried cauliflower with sauce is also a standout dish.
We also tried the duck pate, which was elegantly served on a wooden spoon, and garnished with pistachios and raspberry preserves — a true treat.
Scallops and an accompanying sauce were also good, and the smoked baba ghanouj was particularly memorable.
The glazed shrimp was soft and perfectly cooked, although some may find the sauce a bit overpowering. However, the mushroom steak that I ordered medium-well arrived well done, and the chicken skewers we tried were not very impressive.
Pricing is reasonable. We spent only SR109 (roughly $29) for two. Service is excellent, with meals arriving within minutes, and the staff are friendly and attentive.
The Door is a small venue with limited seating, so booking is essential. The casual and relaxed ambiance makes it an ideal spot to enjoy a good meal.
Recipes for Success: Chef Davisha Burrowes offers advice and a tasty recipe
RIYADH: The Mediterranean dining venue The Lighthouse, founded in the UAE, recently opened its first Saudi outpost in Riyadh’s Diplomatic Quarter.
“I like to describe the Lighthouse menu as a celebration of fresh and seasonal ingredients that represent the Mediterranean culturally as a whole,” says its executive chef Davisha Burrowes. “I think it’s a perfect balance between East and West.”
Burrowes — who grew up in Barbados — caught the culinary bug early.
“I was around nine years old when I started cooking,” she says. “And that just grew around the age of 14 or 15. I did a few competitions in Barbados, and from there, I took my degree in culinary arts, worked around the world in different cuisines, then finally landed with the Lighthouse.”
When you started out, what was the most common mistake you made?
I think all young chefs tend to seek perfection. I was definitely overthinking the little things. And when you overthink, you tend to overcomplicate and overseason. and throughout the years, with growth from maturing as a chef, I will tell anyone that lasts this morning.
What’s your top tip for amateur chefs?
Experiment. Don’t be afraid to try new things — new flavors, new blends. Go with the flow a little bit, and don’t be so hard on yourself. Some of the best recipes, by a lot of chefs around the world, have been born through mistakes.
What one ingredient can instantly improve any dish? And why?
Probably a fresh squeeze of lemon. It brightens, it lifts, it cuts through very rich flavors as well. But personally, I think the best ingredient you can put in a dish is love, cooking with your heart, with your passion, just enjoying it and giving respect to each ingredient, whether it’s something as humble as an onion or a piece of foie gras.
When you go out to eat, do you find yourself critiquing the food?
It depends. If I go to somewhere casual, you know, I take it for what it is. I manage my expectations. I also work within hospitality, so I know there can be certain challenges within the back of house and within the operation. But if I’m going somewhere where I have high expectations, then I hold them to a certain level.
What’s your favorite cuisine?
I love Japanese cuisine. I worked in Japanese cuisine for two years, so I love a good selection of Nigiri platter. It needs precision, but it’s very, very simple.
What’s your go-to dish if you have to cook something quickly at home?
I love cooking spaghetti carbonara. It has very few ingredients, it takes minimal effort, but it also has its intricacies.
What’s your favorite dish to cook?
If time’s not a factor, then it’s a barbecue. Going back to my roots, I’m from the Caribbean, and we do a lot of barbecue — it’s always summer in the Caribbean, so we do a lot of cooking outdoors. So, definitely a barbecue feast or a grazing plate.
What customer behavior most annoys you?
I wouldn’t say it necessarily “annoys” me, but I do get a little disappointed when some ingredients are swapped out of dishes — especially ingredients that are essential to the harmony of the dish. As chefs, we spend a lot of time curating dishes, making sure the flavors are balanced, so when ingredients are swapped out, it just changes the whole experience that we’re trying to offer.
As a leader, what are you like? Are you a disciplinarian? Or are you more laid back?
I prefer to inspire rather than intimidate. I’m very hands-on in the kitchen. I like to lead by example. I think that as a chef — or as a leader in any field — it’s important that the team see you do it, so they can have the encouragement to do it on their own.
Chef Davisha’s charred aubergine with labneh and hot honey harissa
(Serves 2)
Ingredients:
For the Charred Aubergine:
1 large eggplant (aubergine)
1 tbsp olive oil
2 tbsp labneh (or see Labneh Mix below)
1 tbsp hot honey harissa (see Hot Honey Harissa below)
1 tsp toasted pine nuts
A few fresh chives, finely chopped
Salt and pepper to taste
For the Labneh Mix (optional, for a more flavorful labneh):
60g labneh
0g Greek yogurt
Pinch of table salt
1 tsp fresh lemon juice
For the Hot Honey Harissa:
20g butter
10g olive oil
3g harissa paste (or more for extra heat)
1g crushed chili flakes
5g smoked paprika
10g honey
INSTRUCTIONS:
Char the Aubergine: Preheat a grill pan or BBQ to high heat. Brush the aubergine halves with olive oil and season with salt and pepper.
Place cut-side down on the hot grill and cook until charred and softened (about 6-8 minutes per side). For a true smoky flavor, roast directly over a gas flame or in a preheated oven at 220°C for 20 minutes.
Prepare the Labneh Mix (optional): In a bowl, whisk together labneh, Greek yogurt, salt, and lemon juice. Adjust seasoning to taste.
Make Hot Honey Harissa: In a small saucepan, melt the butter and olive oil over medium heat.
Add the harissa paste, chili flakes, smoked paprika, and honey. Stir well and cook for 2 minutes until fragrant. Remove from heat.
Assemble: Place the charred aubergine on a serving plate. Dollop with labneh (or labneh mix), drizzle generously with hot honey harissa, and scatter toasted pine nuts and chopped chives on top.
At-home tips
Labneh Substitute: If you don’t have labneh, use thick Greek yogurt, strained through a cheesecloth or coffee filter for a few hours to mimic labneh’s rich texture.
Char at Home: If you don’t have a grill, broil the aubergine in your oven or cook it in a cast-iron pan to achieve a similar smoky effect.
Harissa Hack: No harissa paste? Mix 1 tbsp tomato paste with 1 tsp chili flakes, ½ tsp cumin, and a pinch of smoked paprika for a quick substitute.
Honey Choices: Use mild, floral honey for a more balanced sauce or a spicy honey to really turn up the heat.
Where We Are Going Today: Korean Palace Restaurant in Riyadh
- The cheese tteokbokki came bubbling in a hot stone bowl, spicy and rich, with gooey cheese melting into the sweet chili sauce
Tucked away on Al-Takhassusi Street, Korean Palace is one of Riyadh’s oldest spots for Korean cuisine, and a nostalgic throwback for those who value flavor over flash.
It’s visibly dated, with worn interiors and a lingering scent that suggests it could benefit from a deep renovation. Still, what it lacks in ambiance, it more than makes up for in taste.
We started with complimentary Korean sides, pickled radish, kimchi, and marinated greens, a generous and flavorful tradition that sets the tone. Then came a table full of classics, each arriving surprisingly fast.
The highlight of the evening? The transparent glass noodles, chewy, perfectly seasoned, and bursting with umami. This was hands down the best dish, and one I’d return for.
The cheese tteokbokki came bubbling in a hot stone bowl, spicy and rich, with gooey cheese melting into the sweet chili sauce.
We also ordered the bibimbap, served hot with colorful vegetables and beef, and the beef sizzling plate, which was tender and satisfying.
The dumplings, delicately wrapped in cabbage leaves, were comforting but mild. The only miss was the tofu soup, which fell flat in flavor and didn’t deliver the depth I expected.
Despite the outdated setting, the overall food quality was impressive. It’s a place that reminds you why people still queue up for spots like this, for food that feels home-cooked, unapologetically traditional, and generously portioned.
Don’t come expecting a trendy hangout. Come for hearty Korean food that gets the job done.
