Innovating Prostate Cancer Care: SYNC-T, Proteogenomics, and Culturally Tailored Education at AACR 2024

Exciting advancements in prostate cancer research, shared at the AACR 2024, are transforming the outlook for patients grappling with the disease. Cutting-edge developments such as SYNC-T, a novel treatment, are offering newfound hope for an illness marked by limited options and high mortality rates. Additionally, proteogenomic studies are unraveling the complexities of prostate cancer progression, particularly across diverse ancestries. Moreover, targeted interventions like culturally tailored educational videos are playing a pivotal role in heightening awareness and promoting early screening practices, particularly within vulnerable communities.

Promising Results in Biologic Drug-Device Combination Immunotherapy

A novel treatment, SYNC-T, offers hope for patients with metastatic castrate-resistant prostate cancer (mCRPC), a condition with limited treatment options and high mortality rates. Prostate cancer presents a challenge with its immunologically “cold” tumor microenvironment, hindering the effectiveness of existing immunotherapies due to their low response rates and high toxicity levels among patients. Therefore, an innovative treatment approach has been developed to stimulate a systemic antitumor immune response for mCRPC. Known as SYNC-T, this treatment, pioneered by Dr. Charles Link and his team, combines a two-step strategy targeting the tumor directly. Firstly, a cold-temperature probe induces oncolysis of cancer cells, prompting the release of tumor-specific neoantigens. Following this, a fixed-dose multitarget biologic drug named SV-102 is infused into the tumor, activating the immune system. SV-102 comprises active pharmaceutical ingredients, including anti-PD-1 and anti-CTLA4 antibodies, alongside CD40 and TLR9 agonists.

Safety and efficacy results of a Phase I Clinical Trial, presented at the AACR Annual Meeting 2024 showed promising clinical responses, with 11 out of 13 evaluable patients experiencing positive outcomes, including complete and partial responses. Moreover, SYNC-T demonstrated lower toxicity compared to existing immunotherapies for prostate cancer. Dr. Link highlighted the potential of SYNC-T to expand the role of immunotherapy in mCRPC treatment, especially given its compatibility with standard medical procedures.

“Our results indicate that SYNC-T is associated with a high response rate without generating severe toxicity in this initial group of patients, which opens up opportunities to expand the role of immunotherapy in mCRPC,” he summarized. “Further, this approach uses standard procedures already employed by urologists and radiologists, which means the treatment could potentially be rapidly adopted by treating physicians.”

Proteogenomic Signatures in Prostate Cancer Progression by Ancestry

A study also presented at the AACR 2024 found that certain proteogenomic signatures in prostate cancers of men from African and European ancestries were linked to a higher risk of metastasis and/or recurrence of the disease. Researchers in the field of proteogenomics, which uses a combination of proteomics and genomics, have conducted a proteogenomic analysis on tissue samples from early-stage prostate cancer in order to better understand the disease development. Tissue samples from 57 patients of African ancestry and 55 patients of European ancestry, obtained from the Center for Prostate Disease Research (CPDR), were analyzed. Differences in protein expression and DNA mutations associated with disease progression were discovered. Essentially, their findings included mutation signatures and recurring changes in DNA copy numbers, as well as heightened protein expression in both groups. These changes were associated with an elevated risk of disease progression, characterized by biochemical recurrence (BCR) and/or metastasis following surgery.

Some specific examples were listed: proteins linked to the risk of disease recurrence and metastasis varied between patients of African and European ancestries. Patients of African ancestry showed higher expression of certain proteins related to oxidative phosphorylation, while those of European ancestry had increased expression of apolipoproteins in cholesterol metabolism. Additionally, prostate cancer in European ancestry patients exhibited more frequent gene alterations at chromosomes 3p, 17p, and 18q, while African ancestry patients showed alterations at chromosomes 1p, 1q, 3q, 13q, and 19p. Furthermore, mutations associated with aging were more prevalent in European ancestry patients, while signatures related to DNA repair deficiency were more common in African ancestry patients.

Culturally Sensitive Video to Boost Prostate Cancer Awareness in Black Men

Findings of an investigation have revealed that a culturally sensitive video targeting Black men increases awareness and knowledge of prostate cancer. The video resulted in 97% of surveyed participants recognizing a higher prostate cancer risk in Black men, with a further 93% expressing willingness to undergo screening. 

In the United States, Black men experience the highest incidence of prostate cancer, with 184.2 new cases per 100,000 individuals, contrasted with 111.5 new cases per 100,000 individuals among white men, as reported by the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program. Additionally, Black men are 2.2 times more prone to prostate cancer-related mortality compared to their white counterparts, according to data from the National Center for Health Statistics.

Developed by Mallorie C. Jones and colleagues, the 10-minute video (a snippet of which was presented at the AACR Annual Meeting 2024) debunked common myths and was well-received at local community events. Jones emphasized that research suggests this gap may stem from limited healthcare access and the perpetuation of misconceptions. “Our study aimed to address these barriers by providing education from trustworthy and reliable sources in settings that were easily accessible to members of the community.” Of 619 men aged 40 and above surveyed, 97% correctly identified that Black men are more likely to develop and die from prostate cancer compared to 74% at baseline. Moreover, 98% found the information provided useful, 97% deemed it credible, and 94% believed the video could enhance awareness about prostate cancer among Black men. Additionally, 93% expressed interest in getting screened, with the majority opting for on-site screening. 

Transformative Advances in Prostate Cancer Care

These breakthroughs highlight the need for varied approaches in tackling prostate cancer. SYNC-T offers a significant stride in immunotherapy, providing tailored treatment with promising results. Additionally, proteogenomic research illuminates genetic factors driving disease progression, enabling personalized interventions. Together with culturally sensitive education efforts, such as the video for Black men, these advancements aim to revolutionize outcomes and address disparities in prostate cancer care.

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Author

Bernice Lottering