Drugs like PARP inhibitors and chimeric antigen receptor (CAR) therapies, and advancements in artificial intelligence in drug discovery, have spurred hope for improved cancer care in the past year. Rigorous research has paved the way for a declining cancer death rate – by 33% to be precise – since the early 1990s, according to a report by American Cancer Society, although the affordability gap still needs bridging. As World Cancer Day was observed on February 4, what does the future of cancer treatment look like in 2034?
“I anticipate that the golden age of immunotherapy will continue to yield new exciting approaches.”
John Maher, CSO of Leucid Bio
Nearly a decade ago, it was thought that immunotherapy and precision medicine were going to be the sought-after approaches to treating cancer, according to the American Cancer Society. Now, ten years down the line, ample research into these fields could set the precedent for cancer treatment in the future.
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Immunotherapy expected to boost cancer care
“I anticipate that the golden age of immunotherapy will continue to yield new exciting approaches,” said John Maher, chief scientific officer (CSO) at U.K.-based Leucid Bio. “We are also likely to witness the development of better off-the-shelf cell therapies that achieve more durable efficacy alongside the development of patient-derived CAR-T drugs that can be produced in an ultra-rapid and more scalable manner. In vivo CAR-T generation is also a potential runner in this field, provided that targeting issues can be addressed.”
With CAR-T cell therapies like Kymriah, Yescarta, Tecartus and Carvykti obtaining the go-ahead from the U.S. Food and Drug Administration (FDA) to target antigens like CD19 and BCMA, which are often expressed in blood cancers, engineering immune cells to battle cancer cells holds promise.
Although, CAR-T does come with its set of challenges and that’s where other cell therapies, like CAR-natural killer (NK), could step in. While still in the clinic, CAR-NK therapies work by alerting NK cells in the body to fight cancer. They do not come with side effects like cytokine release syndrome (CRS) and neurotoxicity, which have been linked to CAR-T. Moreover, CAR-NK therapies have proven their grit in clinical studies, where they have been found to be more effective in attacking cancer cells as they can target cell death independent of tumor antigen, as opposed to CAR-T therapies.
Meanwhile, immunoconjugates are showing substantial promise, according to Liam Tremble, principal scientist at Poolbeg Pharma. These are drugs that are made up of an immune agent like a monoclonal antibody as well as a molecule designed to kill cancer cells. Together, they deliver specific cargo to cancer cells in a precisely targeted way.
“A few years ago, we were still using the ‘one size fits all’ approach. Now we have moved towards a personalized approach, but there is still much further to go if we are to meet the terms of real precision medicine.”
Lars Nieba, CEO of Engimmune Therapeutics
This promise is seen in the case of antibody drug conjugates (ADCs). Touted as the dawn of a new era in cancer treatment, the recent ADC buying spree is telling of the growing interest in the sector. One of the latest ADCs to be approved, ImmunoGen’s landmark ovarian cancer drug Elahere, has now been bought by multinational company AbbVie. Pharma giants Bristol Myers Squibb and GSK have swept up ADCs like ORM-6151 and HS-20089, both of which have been cleared for the clinic.
Maher expects antibody-based therapeutics to continue to yield new drugs like immunomodulatory agents and antibody drug conjugates “that deliver ever more powerful poisons in a selective manner to tumor cells.”
This is a view held by various researchers. Lars Nieba, chief executive officer (CEO) of Switzerland-based Engimmune Therapeutics, believes that ADCs will “play a very important role in solid tumors, thanks to our much-improved understanding of the biology of target and toxin.”
Nieba also thinks that we will see drugs like T-cell receptor (TCR)-based therapies, which can infiltrate solid tumors, shaping the future of cancer care.
“These tumor-infiltrating drugs will be of particular help in tackling advanced cancers, where tumors are bigger and more developed,” said Nieba.
Engimmune’s approach is to employ soluble TCRs to target antigens, which according to Nieba, significantly raises the chance of finding suitable, cancer-specific targets.
Is precision medicine poised to take on cancer?
Besides immunotherapy, precision medicine is a field that is growing rapidly. Precision medicine takes a patient’s genes, environment, and lifestyle into account, to enable doctors to match a patient with the best-suited therapy.
“A few years ago, we were still using the ‘one size fits all’ approach. Now we have moved towards a personalized approach, but there is still much further to go if we are to meet the terms of real precision medicine,” said Nieba, who explained that combination therapies might be a step in the right direction when it comes to tailoring patient-specific drugs.
Echoing these thoughts, Catherine Pickering, said: “We know that some people respond better to targeted therapies depending on the genetic profile of their tumor, but strong advances are being made to analyze other components of the tumor microenvironment such as immune and stromal influences. These are also important factors contributing to innate and adaptive tumor resistance pathways.”
Pickering pointed out that non-invasive multi-omic approaches can help predict the best drug combination to match a particular person’s tumor type. This could give rise to the use of tissue-agnostic therapies, which are drugs that treat cancer based on the genetic and molecular features of the cancerous cells. This way, a single drug can address various kinds of cancer, regardless of the target organ or tumor type.
So far, larotrectinib and entrectinib, which disable the NTRK gene, and the immune checkpoint inhibitor pembrolizumab, known by its brand name Keytruda, are among the various tissue-agnostic therapies cleared by the FDA.
With the global market for precision medicine valued at more than $29 billion as of 2023, according to Markets and Markets, it is poised to cross $50 billion in the next four years.
Patients will have more access to targeted and personalized treatments that are designed specifically for their cancer, explained Tremble.
As a lot of current treatments that are trumpeted as revolutionary, unfortunately, don’t work for everyone, Tremble said: “By personalized, we mean selecting a treatment based on the genetic and protein profile of a tumor. Using these profiles, we can enhance the number of patients for whom a therapy is successful, and we can increase its effectiveness.”
Where do cancer vaccines stand?
This might also hold true for personalized vaccines. Hailed as a step forward in cancer research, cancer vaccines are a form of immunotherapy that trains the body to protect against cancer cells. Personalized vaccines, which intertwine the science behind vaccine technology and personalized medicine, will be a significant advancement in cancer research, according to Pickering.
The investigational vaccine mRNA-4157/V940, born out of a collaboration between Moderna and pharma giant Merck, was awarded breakthrough designation last year. The vaccine contains a synthetic mRNA that codes for up to 34 neoantigens, and can stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient’s tumor.
To add to that, German immunotherapy company BioNTech’s expansion of its oncology program has boosted its cancer vaccine to phase 2 in the clinic. Its investigation vaccine autogene cevumeran exhibited vaccine-induced immunity, which aided the delayed tumor recurrence in patients with pancreatic cancer, in a phase 1 trial.
“There have been some really exciting early-stage results for personalized pancreatic cancer vaccines in 2023, and I hope these continue to show good efficacy in later-stage trials over the next few years,” said Pickering.
CRISPR and the future of cancer treatment
While precision medicine is gaining ground, CRISPR technology seems to be living up to the hype lately. In cancer, gene editing tools aim to fix harmful mutations and thereby control tumor progression.
“Techniques such as CRISPR-Cas9 may play a role in cancer therapy by editing or repairing faulty genes linked to cancer,” said Jason Loveridge, CEO of German cancer drug company 4SC. “With further research and refinement, gene editing could offer targeted treatments or cures for specific types of cancer” in the future.
A study published in Nature revealed that with the help of CRISPR, researchers were able to genetically redirect T cells to mutant neoantigens. The non-viral gene editing approach that was performed in the study was designed to knock in and out genes in order to improve T cell function. Plus, the edits helped circumvent immunosuppression, and so, the T cells could elicit a response despite many antigen encounters.
The future of cancer diagnosis: AI, virtual biopsies, and molecular profiling
In addition to CRISPR and precision medicine, approaches to imaging and detection could also shift in the future, in an effort to speed up diagnosis and cancer treatment.
Some experts think that artificial intelligence (AI)-based profiling can help guide the therapeutic approach that is right for a patient. And, virtual biopsies based on AI-read scans and liquid biopsies based on circulating tumor cells or genetic material, “will likely replace physical biopsies,” according to Germo Gericke, chief medical officer at German company Ariceum Therapeutics.
Sparing invasive procedures, virtual biopsies aim to reduce the number of biopsies and improve their accuracy. However, liquid biopsies, which is generally a blood draw, may miss certain mutations sometimes, and test sensitivity challenges could affect a diagnosis. So, further research and development may be needed to convince patients of their boon.
Nevertheless, liquid biopsies could help monitor disease progression, explained Loveridge. This could lead to biomarker-driven and personalized treatments based on the kind of tumor.
Like with virtual biopsies, Pickering foresees that AI will become an increasingly important tool in cancer research.
“From modeling drug discovery targets, to drug-drug interactions, to image analysis, the potential opportunity of AI is huge. It ultimately promises to cut down time to getting successful drugs into the clinic,” said Pickering.
Moreover, in diagnostics, we now have “techniques that allow us to interrogate malignant tumors with much greater depth than ever before,” according to Maher.
Stressing how the molecular profiling method of spatial transcriptomics can give more of an idea of the metropolis of tumor microenvironment, Maher said: “This provides a more holistic and integrated view of how malignant and stromal cells communicate with and support each other, guiding us as to which nodes are vital to the persistence of the malignant state.”
Can the U.S. combat rising cancer death rates and treatment costs?
Now, with initiatives like the U.S. Cancer Moonshot program reignited by President Biden in 2022, there is more emphasis on widening treatment options. Although the aim of the program to halve cancer death rates in 25 years might seem far-fetched to some, the grants offered to some studies, which include an mRNA-cancer vaccine project, could hold out hope to patients.
“Frequent hospital visits, including to high-tech centers that may be very far away from some patients’ homes, is a major burden… As we move to oral and subcutaneous treatments, patients will be able to treat themselves at home.”
Liam Tremble, principal scientist at Poolbeg Pharma
However, this would only be truly impactful if the financial burden were to be reduced drastically. In the U.S., the national economic burden associated with cancer care was $21.09 billion, out of which patient out-of-pocket costs were a whopping $16.22 billion, back in 2019. And, the rest – $4.87 billion – amounts to patient time costs, according to a report by the National Cancer Institute. Patient time costs reflect the value of time that patients spend traveling to and from hospitals, waiting for care, and receiving care.
Besides, if patients were to have fewer hospital visits, this could improve their quality of life, Tremble pointed out.
“Frequent hospital visits, including to high-tech centers that may be very far away from some patients’ homes, is a major burden. It will always be crucial to visit hospitals for scans during and post treatment, but many patients have to attend frequently and for prolonged inpatient stays just to receive their therapy,” said Tremble. “As we move to oral and subcutaneous treatments, patients will be able to treat themselves at home.”
While the financial challenges prevail, as more drugs hit the market and more insurance plans cover additional cancer care expenses, there might be some hope for more affordable cancer treatments in the future. And, with further strides in personalized medicine, minimizing overtreatment, could help cut costs as well. Still, we will have to be on the lookout for whether these advances make it to the bedside or not.
This article was originally published by Jim Cornall in February, 2023, and has since been updated by Roohi Mariam Peter in February, 2024.
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