Cancer Cell Biology – New Theory of Cancer https://www.newtheoryofcancer.com Recent & Emerging Research Elucidations Fri, 17 May 2024 19:54:04 +0000 en-US hourly 1 https://wordpress.org/?v=6.7.1 Neospora caninum, a Protozoan Killing Dogs, “Might Be Key” to “Total Regression of Tumors” https://www.newtheoryofcancer.com/2024/05/17/neospora-caninum-a-protozoan-killing-dogs-might-be-key-to-total-regression-of-tumors/ Fri, 17 May 2024 19:54:02 +0000 https://www.newtheoryofcancer.com/?p=153

Neosporosis, caused by the intracellular parasite Neospora caninum, presents a significant challenge in veterinary medicine, leading to serious and life-threatening neurological issues in dogs, and costing the industrial cattle industry billions each year. N. caninum does not infect humans, making […]

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Neosporosis causes paralysis and death in canines. This dog’s symptoms began in the hind legs, requiring a wheelchair for mobility.

Neosporosis, caused by the intracellular parasite Neospora caninum, presents a significant challenge in veterinary medicine, leading to serious and life-threatening neurological issues in dogs, and costing the industrial cattle industry billions each year. N. caninum does not infect humans, making it a potentially safe therapeutic agent.

The study, “Neospora caninum: a new class of biopharmaceuticals in the therapeutic arsenal against cancer“, published in the Journal for ImmunoTherapy of Cancer in 2020, brought to light the game-changing potential of N. caninum in cancer therapy.

The study reported N. caninum effectively destroyed cancer cells and stimulated the immune system to fight tumors. In experiments using a mouse model of thymoma (a type of cancer that affects the thymus gland), researchers observed that injections of live N. caninum tachyzoites, either directly into the tumor or at a distant site, led to significant tumor regression and, in many cases, complete eradication.

Unleashing the Power of the Immune System

The study’s findings point to several key mechanisms by which N. caninum exerts its anti-cancer effects:

  • Direct Cytotoxic Activity: The researchers observed that N. caninum tachyzoites can directly infect and kill cancer cells.
  • Immune System Activation: N. caninum effectively stimulates the immune system, prompting the recruitment of immune cells to the tumor site, effectively transforming what would normally be “cold” tumors (tumors that are not infiltrated by immune cells) into “hot” tumors (tumors that are heavily infiltrated by immune cells).
  • Reprogramming the Tumor Microenvironment: N. caninum alters the tumor’s microenvironment, reducing the presence of immunosuppressive factors that can hinder the immune system’s ability to fight cancer.

The study also highlights the critical role of natural killer (NK) cells, CD8+ T cells, and macrophages in the N. caninum-mediated anti-tumor response. Depleting these immune cell populations through specific antibodies completely abolished N. caninum‘s antitumor activity, underscoring their importance in the process.

NC = Neospora caninum (included a “distant” test)

Advantages Over Existing Therapies

The researchers contrasted N. caninum‘s potential as a cancer therapeutic with the limitations of currently available agents, such as viruses and bacteria, which are sometimes associated with toxicity and safety concerns.

The study authors emphasized these advantages of N. caninum:

  • Safety: Unlike viruses and bacteria that can persist in the body and potentially cause harm, N. caninum is naturally cleared from the system after initiating an immune response, making it a safer alternative.
  • Targeting Efficiency: N. caninum exhibits a remarkable ability to penetrate tumors and cancer cells. This is attributed to its unique apical complex, a specialized structure that allows it to effectively invade a wide range of cell types.
  • Genetic Engineering Potential: N. caninum has a large genome capacity, meaning it can be genetically engineered to carry therapeutic payloads. This opens up possibilities for creating “armed” strains that can deliver additional anti-cancer agents directly to tumor cells.

Promising Results with Human Tumor Model

To further explore the potential of N. caninum for treating human cancers, researchers conducted experiments using a mouse model of Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer. The results were highly encouraging, demonstrating that treatment with N. caninum led to a significant regression of MCC tumors.

Engineering an Enhanced Strain: NC1-IL15hRec

Recognizing the need for even more potent anti-tumor responses, particularly in advanced or refractory cancers, the researchers engineered a strain of N. caninum called NC1-IL15hRec. This strain secretes a human form of interleukin-15 (IL-15), a cytokine that plays a crucial role in stimulating the immune system, particularly NK cells and CD8+ T cells.

Experiments showed that NC1-IL15hRec induced a robust increase in the proliferation and activity of human immune cells. When tested in the mouse model of thymoma, NC1-IL15hRec exhibited superior anti-tumor efficacy compared to the unmodified strain, demonstrating the potential of enhancing N. caninum‘s therapeutic properties through genetic engineering.

A New Frontier in Cancer Immunotherapy

This study represents a significant step forward in the development of novel cancer treatments that harness the power of the immune system. The findings suggest that N. caninum holds immense promise as a new weapon in the fight against cancer. Further research is ongoing to fully unlock its therapeutic potential and bring this innovative approach to the clinic.

]]> A fitness landscape instability governs the morphological diversity of tip-growing cells https://www.newtheoryofcancer.com/2024/04/22/a-fitness-landscape-instability-governs-the-morphological-diversity-of-tip-growing-cells/ Mon, 22 Apr 2024 22:14:33 +0000 https://www.newtheoryofcancer.com/?p=193 Ohairwe et al. demonstrate that an intrinsic mechanical instability in the convergent mechanism of “inflationary” cell growth shared by diverse tip-growing cells leads to a bifurcation (branching) of their fitness landscape. This bifurcation strictly constrains natural tip-growing cell shapes.

]]> Ohairwe et al. demonstrate that an intrinsic mechanical instability in the convergent mechanism of “inflationary” cell growth shared by diverse tip-growing cells leads to a bifurcation (branching) of their fitness landscape. This bifurcation strictly constrains natural tip-growing cell shapes.

]]> Genomic deletions explain the generation of alternative BRAF isoforms conferring resistance to MAPK inhibitors in melanoma https://www.newtheoryofcancer.com/2024/04/22/genomic-deletions-explain-the-generation-of-alternative-braf-isoforms-conferring-resistance-to-mapk-inhibitors-in-melanoma/ Mon, 22 Apr 2024 22:14:32 +0000 https://www.newtheoryofcancer.com/?p=191 Aya et al. show that the production of alternative BRAF mRNA isoforms (altBRAFs), associated with resistance to BRAF inhibitors in melanoma, is caused by genomic deletions rather than by alternative splicing, as previously thought. They also find that altBRAFs are present […]

]]> Aya et al. show that the production of alternative BRAF mRNA isoforms (altBRAFs), associated with resistance to BRAF inhibitors in melanoma, is caused by genomic deletions rather than by alternative splicing, as previously thought. They also find that altBRAFs are present in treatment-naive, non-V600 BRAF-mutant and BRAF wild-type mutant tumors.

]]> The soil microbiome modulates the sorghum root metabolome and cellular traits with a concomitant reduction of Striga infection https://www.newtheoryofcancer.com/2024/04/22/the-soil-microbiome-modulates-the-sorghum-root-metabolome-and-cellular-traits-with-a-concomitant-reduction-of-striga-infection/ Mon, 22 Apr 2024 22:14:32 +0000 https://www.newtheoryofcancer.com/?p=192 The soil microbiome protects sorghum, and likely other crops, from infection with the root parasite Striga hermonthica. Kawa et al. show that soil-borne bacteria modify sorghum root development and root exudate content, likely preventing Striga from penetrating sorghum. This study provides […]

]]> The soil microbiome protects sorghum, and likely other crops, from infection with the root parasite Striga hermonthica. Kawa et al. show that soil-borne bacteria modify sorghum root development and root exudate content, likely preventing Striga from penetrating sorghum. This study provides a framework for developing microbial-based solutions for Striga infestation.

]]> The nociceptive activity of peripheral sensory neurons is modulated by the neuronal membrane proteasome https://www.newtheoryofcancer.com/2024/04/22/the-nociceptive-activity-of-peripheral-sensory-neurons-is-modulated-by-the-neuronal-membrane-proteasome/ Mon, 22 Apr 2024 22:14:31 +0000 https://www.newtheoryofcancer.com/?p=190 Proteasomes are critical for sensory neuron function. Villalón Landeros et al. uncover a specialized proteasome in somatosensory neurons called the neuronal membrane proteasome (NMP). The NMP mediates crosstalk between somatosensory neurons to modulate sensitivity to stimulation. Inhibition of the NMP reduces […]

]]> Proteasomes are critical for sensory neuron function. Villalón Landeros et al. uncover a specialized proteasome in somatosensory neurons called the neuronal membrane proteasome (NMP). The NMP mediates crosstalk between somatosensory neurons to modulate sensitivity to stimulation. Inhibition of the NMP reduces sensitivity to mechanical and painful stimuli in vivo.

]]> Environmentally dependent and independent control of 3D cell shape https://www.newtheoryofcancer.com/2024/04/22/environmentally-dependent-and-independent-control-of-3d-cell-shape/ Mon, 22 Apr 2024 22:14:30 +0000 https://www.newtheoryofcancer.com/?p=188 Using high-throughput light-sheet microscopy, Dent et al. study 3D cancer cell morphogenesis. Environmental cues modulate the opposing roles of non-muscle myosin II (myosin) and microtubules, with varied impacts on RhoGEFs FARP1 and TIAM2. The study underscores the critical interplay between cytoskeletal […]

]]> Using high-throughput light-sheet microscopy, Dent et al. study 3D cancer cell morphogenesis. Environmental cues modulate the opposing roles of non-muscle myosin II (myosin) and microtubules, with varied impacts on RhoGEFs FARP1 and TIAM2. The study underscores the critical interplay between cytoskeletal regulators and the microenvironment, enhancing our understanding of cell behavior in diverse settings.

]]> Distributed X chromosome inactivation in brain circuitry is associated with X-linked disease penetrance of behavior https://www.newtheoryofcancer.com/2024/04/22/distributed-x-chromosome-inactivation-in-brain-circuitry-is-associated-with-x-linked-disease-penetrance-of-behavior/ Mon, 22 Apr 2024 22:14:30 +0000 https://www.newtheoryofcancer.com/?p=189 Szelenyi et al. demonstrate that adult brain XCI is systematically biased toward maternal X-active cells, which is sufficient for disease penetrance of the X-linked Fmr1-KO allele. Furthermore, local XCI mosaicism distinguishes phenotypic outcomes of individuals based on mutant X-active cells populating […]

]]> Szelenyi et al. demonstrate that adult brain XCI is systematically biased toward maternal X-active cells, which is sufficient for disease penetrance of the X-linked Fmr1-KO allele. Furthermore, local XCI mosaicism distinguishes phenotypic outcomes of individuals based on mutant X-active cells populating distinct brain circuits.

]]> Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling https://www.newtheoryofcancer.com/2024/04/22/antibodies-targeting-the-shared-cytokine-receptor-il-1-receptor-accessory-protein-invoke-distinct-mechanisms-to-block-all-cytokine-signaling/ Mon, 22 Apr 2024 22:14:29 +0000 https://www.newtheoryofcancer.com/?p=187 Fields et al. demonstrate the viability of targeting a shared cytokine receptor for comprehensive signaling blockade of all associated cytokines. CAN10 and 3G5, two anti-IL-1RAcP antibodies, target distinct epitopes on this shared receptor and potently block IL-1α, IL-1β, IL-33, IL-36α, IL-36β, […]

]]> Fields et al. demonstrate the viability of targeting a shared cytokine receptor for comprehensive signaling blockade of all associated cytokines. CAN10 and 3G5, two anti-IL-1RAcP antibodies, target distinct epitopes on this shared receptor and potently block IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ signaling.

]]> LXR/CD38 activation drives cholesterol-induced macrophage senescence and neurodegeneration via NAD+ depletion https://www.newtheoryofcancer.com/2024/04/22/lxr-cd38-activation-drives-cholesterol-induced-macrophage-senescence-and-neurodegeneration-via-nad-depletion/ Mon, 22 Apr 2024 22:14:28 +0000 https://www.newtheoryofcancer.com/?p=186 Terao et al. demonstrated how dysregulated cholesterol metabolism drives macrophage senescence and the development of subretinal drusenoid deposits in mice. LXR/CD38 signaling activated by cholesterol reduces NAD+ availability and promotes macrophage senescence. Senolytic agents targeting NAD+ decline and senescent macrophages are […]

]]> Terao et al. demonstrated how dysregulated cholesterol metabolism drives macrophage senescence and the development of subretinal drusenoid deposits in mice. LXR/CD38 signaling activated by cholesterol reduces NAD+ availability and promotes macrophage senescence. Senolytic agents targeting NAD+ decline and senescent macrophages are a potential therapeutic option against early AMD.

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