Interesting<\/p>\n
Experimental drug shrinks advanced kidney tumors, clears cancer in one patient.<\/a><\/p>\n A new Phase I clinical trial provides proof of concept for a potential therapy for treatment-resistant cancers, particularly kidney cancer. In the new study, published in\u00a0Cell Reports Medicine<\/i><\/a>, researchers tested a novel kind of immunotherapy in individuals with different types of cancer.<\/p>\n In a subset of patients with advanced clear cell renal cell carcinoma, the most common and an aggressive form of kidney cancer, the drug successfully reduced\u2014and in one patient completely cleared\u2014the cancer in a subset of patients.<\/p>\n “We studied a very hard-to-treat population,” says David Braun, MD, Ph.D., assistant professor of medicine (medical oncology), of pathology, and of urology, the Louis Goodman and Alfred Gilman Yale Scholar, and the study’s lead author. “The fact that this drug was clinically active and leading to some responses is really encouraging.”<\/p>\n <\/p>\n Cancer cells are adept at evading the body’s immune system. But emerging therapies harness the power of our natural defenses to fight off tumors. Imagine a car full of immune cells driving toward a cancer.<\/p>\n There are several ways to help these cells reach the invader as quickly and accurately as possible: You can add a steering wheel, hit the gas pedal, or take your foot off the brake.<\/p>\n New immunotherapies\u2014treatments that help the immune system more effectively fight cancers\u2014each fit into one of these three groups, Braun says. Immune checkpoint inhibitors and other new immunotherapies, like the one in this study, fall into the last category.<\/p>\n When you get sick, your body ramps up its immune system response to fight off pathogens. “But you don’t want the immune system to always stay in such a ‘ramped-up’ state because then you have all the negative effects of an overactive immune system\u2014like inflammation or autoimmunity,” explains Braun, a member of Yale Cancer Center.<\/p>\n “So, you ultimately want your immune system to return back to its ‘resting’ state.”<\/p>\n Thus, our body also contains natural brakes that regulate immune response. But cancer can evade our immune system by hijacking these brakes, keeping them pressed so immune cells can’t successfully attack the tumor. Some immunotherapies, such as the one studied here, work to treat cancer by helping release the brakes.<\/p>\n Early\u00a0immune checkpoint inhibitors<\/a>\u00a0have changed how doctors treat cancer and are helping people with previously incurable cases live longer. But while these therapies are now standard for several types of cancer, they still do not work for many patients.<\/p>\n “With current ‘standard’ immune checkpoint inhibitors, I think we are at an inflection point,” Braun explains.<\/p>\n “Advanced kidney cancer used to be a uniformly deadly disease, so the fact that these drugs are helping people generally live much longer and potentially even curing a small number of people is really important. But that enthusiasm must be balanced by the reality that, in 2026, the vast majority of people with metastatic kidney cancer will still die from their disease.”<\/p>\n Scientific and clinical studies of this disease are needed to help researchers develop new and improved versions of these therapies, says Braun, who primarily treats kidney cancer and leads a laboratory that studies immunotherapies.<\/p>\n Hematopoietic progenitor kinase 1 (HPK1) is one of the immune system’s brakes, and it’s found within several types of immune cells, including T cells. Studies in animal models have shown that removing, or “knocking out,” HPK1 in immune cells helps animals generate stronger immune responses against cancer.<\/p>\n “But actually inhibiting HPK1 with a drug has been really hard because, one, it is not on the surface of a cell where you can bind it with an antibody and block it, and two, the molecule looks very similar structurally to other important proteins in the cell, and so it has been challenging to develop a drug that only blocks HPK1 but not the other, similar molecules,” Braun says. “Ultimately, it has been difficult to target.”<\/p>\n In their new study, Braun and the study team tested a new drug designed to enter immune cells and deactivate HPK1. They enrolled more than 100 patients with a range of cancer types between 2021 and 2024, many of whom had their cancer progress after multiple prior treatments. It is one of the first times scientists have tested this HPK1 inhibitor in humans.<\/p>\n “Going into the study, it was an unknown as to what type of cancer would respond, or if any would respond,” says Braun.<\/p>\n One of the primary goals of a Phase I clinical trial is to evaluate the safety of new drugs and identify a tolerable dosage. The researchers started participants on a low dose of the drug and gradually increased it until side effects arose, thus identifying the highest dose that was still safe.<\/p>\n “For Phase I studies, the main thing we’re trying to establish is if there is a safe dosage,” says Braun. “Beyond that, demonstrating some clinical activity is an encouraging step.”<\/p>\n Among the cancer types studied, clinical activity was seen specifically in patients with clear cell renal cell carcinoma (ccRCC).<\/p>\n Among the 22 participants with this kind of cancer, all of whom had previously received standard treatments for kidney cancer and had their cancer progress, the drug completely cleared the disease in one individual and reduced tumor size in two others. In three other participants, the cancer remained stable for many months, and in one individual, up to 25 months.<\/p>\n “And these are all patients that have been heavily pretreated,” Braun says. “They have all had a number of different therapies, in some cases three, four, or five different types of treatments and had cancer progression through each of them.”<\/p>\n They also assessed whether the drug was actually reaching HPK1 inside the T cells. Using blood samples from patients, they developed a test that measured biological indicators of HPK1 inhibition. The approach confirmed that the drug was successfully inhibiting its target.<\/p>\n Furthermore, the team took biopsies of tumors from participants before and after starting the treatment. The samples showed that certain populations of immune cells increased in the tumor post-treatment. “This drug is doing what we think it should both biologically and molecularly,” Braun says.<\/p>\n The team isn’t sure why the drug appeared most active in clear cell kidney cancer. “There was no specific reason that we could tease apart about why kidney cancer specifically would be susceptible to this drug,” Braun says. “That is still an open question, and more studies are needed to know whether this approach might be helpful for other cancer types.”<\/p>\n Doctors have historically considered many advanced cancers, or cancers that have spread to other parts of the body, as incurable. Immunotherapies indicate that one day doctors may be able to cure previously incurable cancers.<\/p>\n “But we have a huge way to go from proof of concept to making this the common outcome,” Braun says.<\/p>\n “Through both laboratory-based and clinical studies, we hope to chip away at this. Bit by bit, as a field, we will get closer and closer to immunotherapies that control cancer and even cure more people.”<\/p>\n <\/p>\n","protected":false},"excerpt":{"rendered":" Interesting Experimental drug shrinks advanced kidney tumors, clears cancer in one patient. A new Phase I clinical trial provides proof of concept for a potential therapy for treatment-resistant cancers, particularly kidney cancer. In the new study, published in\u00a0Cell Reports Medicine, researchers tested a novel kind of immunotherapy in individuals with different types of cancer. In … Continue reading “”<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[41],"tags":[],"class_list":["post-116811","post","type-post","status-publish","format-standard","hentry","category-health-medicine"],"_links":{"self":[{"href":"https:\/\/milesfortis.com\/index.php?rest_route=\/wp\/v2\/posts\/116811","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/milesfortis.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/milesfortis.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/milesfortis.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/milesfortis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=116811"}],"version-history":[{"count":1,"href":"https:\/\/milesfortis.com\/index.php?rest_route=\/wp\/v2\/posts\/116811\/revisions"}],"predecessor-version":[{"id":116812,"href":"https:\/\/milesfortis.com\/index.php?rest_route=\/wp\/v2\/posts\/116811\/revisions\/116812"}],"wp:attachment":[{"href":"https:\/\/milesfortis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=116811"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/milesfortis.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=116811"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/milesfortis.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=116811"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}What is immunotherapy?<\/h2>\n
HPK1 inhibitor successfully treats kidney cancer<\/h2>\n