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2023’s most exciting medical research breakthroughs

MDlinx Dec 22, 2023

As the year draws to a close, MDLinx takes a look at five major research breakthroughs with exciting clinical applications that emerged during 2023. 


mRNA vaccines to treat cancer


mRNA vaccine technology is key to the new COVID-19 vaccinations. And according to Vincent F. Carr, DO, member of the MDLinx medical advisory board, the potential role of mRNA vaccines has expanded into the cancer space.


In a phase 1 study of 16 patients with pancreatic ductal adenocarcinoma (PDAC) who were treated with personalized mRNA vaccine, eight showed a strong anti-tumor response and had longer recurrence-free survival during 2-year follow-up, compared with the participants who did not mount an immune response.

Rojas LA, Sethna Z, Soares KC, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature. 2023;618:144–150.


The study authors concluded that the individualized neoantigen vaccination, in combination with immunotherapy and chemotherapy (atezolizumab and mFOLFIRINOX, respectively) was “safe, feasible, and generates substantial neoantigen-specific T cells in 50% of unselected patients with resectable PDAC.”

PDAC isn’t the only cancer for which mRNA vaccines have shown effectiveness. In February 2023, the US FDA awarded breakthrough therapy designation to the combination of a personalized mRNA vaccine (mRNA-4157/V940) and a monoclonal antibody (pembrolizumab) for adjuvant treatment of patients with high-risk melanoma following complete resection.

Moderna and Merck announce mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with KEYTRUDA® (pembrolizumab), was granted breakthrough therapy designation by the FDA for adjuvant treatment of patients with high-risk melanoma following complete resection [press release]. Moderna, Merck. February 22, 2023. 



The biologicals for cancer have significant downsides, [but] the RNA vaccines, at this point, are not being reported as having the same adverse effects.

Despite this turning point, Dr. Carr tells MDLinx, the "misinformation against the RNA vaccines is severe and very misleading, depriving cancer patients of the benefits.”


Potential tumor treatment of the future



A chemotherapy has been developed to target proliferating cell nuclear antigen (PCNA). The new agent, AOH1996, selectively kills cancer cells and has been shown to destroy solid tumors in a preclinical study.

Gu L, Li M, Li CM, et al. Small molecule targeting of transcription-replication conflict for selective chemotherapy. Cell Chem Biol. 2023;30(10):1235–1247.e6.


“Data suggests that PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells,” said senior author Linda Malkas, PhD, in a press release.

Vuong Z. City of Hope scientists develop targeted chemotherapy able to kill all solid tumors in preclinical research [press release]. City of Hope. August 1, 2023.

Dr. Malkas is a professor at City of Hope’s Department of Molecular Diagnostics and Experimental Therapeutics. 


“Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out,” she said, “only in planes carrying cancer cells. [It] can suppress tumor growth as a monotherapy or combination treatment in cell and animal models without resulting in toxicity.”

MDLinx advisory board member Courtney Manser, MD, CCFP, explains the significance of this research: “There are ongoing phase 1 clinical trials for AOH1996—a medication that has shown promise in preclinical trials, in which it kills solid tumors,” she says.

This may be the cancer treatment of the future.


Ultra-processed food’s effect on mental health


“The role of ultra-processed foods in the development of depression and other psychiatric conditions is an important 2023 breakthrough,” Robert M. Berman, MD, PhD, MBA, a Manhattan-based psychiatrist, tells MDLinx.

Researchers associated with Harvard TH Chan School of Public Health prospectively examined the association between ultra-processed foods (UPF) and its components with incident depression.

Samuthpongtorn C, Nguyen LH, Okereke OI, et al. Consumption of ultraprocessed food and risk of depression. JAMA Netw Open. 2023;6(9):e2334770.

They assessed diet using food-frequency questionnaires every 4 years in 31,712 women (mean age: 52 years at baseline).


Compared with those in the lowest quintile of UPF consumption, those in the highest quintile had between a 1.3- and a 1.5-fold increased risk of incident depression, depending on how depression was defined. 

Notably, “models were not materially altered after inclusion of potential confounders,” the researchers emphasized. Artificial sweeteners and artificially sweetened beverages were particularly implicated. 

Similar findings were obtained by a group of Australian researchers who studied data from 23,299 adults in the Melbourne Collaborative Cohort Study.

Lane MM, Lotfaliany M, Hodge AM, et al. High ultra-processed food consumption is associated with elevated psychological distress as an indicator of depression in adults from the Melbourne Collaborative Cohort Study. J Affective Disorders. 2023;335:57–66.

They found increased odds of “elevated psychological distress” (an “indicator of depression”) with the highest compared to the lowest intake of UPF—even after adjusting for age, sex, and BMI. 


Dr. Berman elaborates on this study, saying that further data on the physical and mental health effects of UPF “could ultimately lead to potential treatment enhancements using a more holistic approach involving nutrition, diet, and exercise in addition to traditional medications and psychotherapy.” 


Mobility in patients with spinal cord injury


Researchers in Switzerland used artificial intelligence (AI) to enable a man with spinal cord injury (SCI)–induced tetraplegia to walk.

Lorach H, Galvez A, Spagnolo V, et al. Walking naturally after spinal cord injury using a brain-spine interface. Nature. 2023;618:126–133.

SCI “interrupts the communication between the brain and the region of the spinal cord that produces walking, leading to paralysis,” the researchers explained.



In their groundbreaking study, communication was restored by creating a “digital bridge” between the brain and the spinal cord. This “brain-spine interface” (BSI) consists of implanted recording and stimulation systems that directly link cortical signals and analogue modulation of epidural electrical stimulation, targeting the specific spinal cord regions that play a role in walking.

For over a year, the patient maintained his ability to stand, walk, climb stairs, and even traverse “complex terrains.” Additionally, the BSI improved neurological recovery achieved during neurorehabilitation, such that he is able to walk with crutches—even when the BSI is switched off.

Rex Marco, MD, Chief of Reconstructive Spine Surgery and Orthopedic Oncology at Houston Methodist, calls this innovation “exciting and filled with potential.”

Dr. Marco himself lives with quadriplegia as a result of an SCI sustained during a biking accident. “Until now, I thought that research could help people with SCI to have a better life. But the word ‘cure’ wasn’t in my vocabulary,” he tells MDLinx. “This innovative approach can pave the way for more people with SCI to regain use of their arms and legs. The ‘cure’ for paralysis may actually be on the horizon.”


Neurostimulation to aid stroke recovery


Deep brain stimulation (DBS) has been used in a phase 1 study of patients with moderate to severe upper extremity hemiparesis resulting from stroke.

Baker KB, Plow EB, Nagel S, et al. Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial. Nat Med. 2023;29:2366–2374.

DBS was applied to the dentate nucleus of the cerebellum.



Of the 12 patients in the trial, 9 showed improvements in motor impairment and function. Among the participants with some preservation of distal motor function at baseline, the improvements almost tripled their initial scores. In this study, improvements were achieved regardless of the amount of time that had elapsed since the stroke—in some cases as long as 3 years.

The clinical improvements were corroborated by findings of positron emission tomography (PET) scans that showed significant increments in brain metabolism in the areas of the brain that had been impacted by the stroke. The authors called DBS a “promising tool for modulation of late-stage neuroplasticity for functional recovery,” and noted it was both safe and feasible. 

Steven Cramer MS, MSc, who is a professor in the Department of Neurology at the David Geffen School of Medicine, UCLA, regards this as an “important and exciting” advance in treating patients with stroke.

“Unfortunately, at present, there are few options to boost recovery for patients who experience disability following stroke, although a number of restorative therapies are under study to improve outcomes,” he tells MDLinx. “[The] encouraging data presented in this study, coupled with favorable PET biomarker data, lay the groundwork for a phase 2 controlled clinical trial of this promising approach.”

What this means for you

MDLinx advisory board members note some of 2023's most exciting medical research breakthroughs, including those related to advancements in mRNA technology for cancer treatment and AI for neurorehabilitation. Also of note includes research into the role of "ultra-processed" foods on mental health and DBS for improved stroke recovery.


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