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UAS Biokank - Coggle Diagram
UAS Biokank
Cancer Treatment
Definisi
Cancer treatment is a multifaceted field depends heavily on the tumor type, stage, and the patient's specific biological profile, including age and comorbidities
Traditional Treatment
Radiotherapy (RT)
Mechanism
Radiation removes electrons from intracellular molecules, generating reactive free radicals that attack DNA -> triggers P53 -> apoptosis & chromosome damage -> mitotic death
Administration
Fractioned (small doses) over weeks. This allows normal cells, which repair DNA faster than cancer cells, to recover between sessions, thereby widening the survival gap between healthy and malignant tissue
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Surgery may insufficient if:
- tumor metastazied
- the location is hard for surgery
- different cancer need different dose
Sideeffect that limit the dose:
- Damage Gastrointestinal tract -> nausea, vomiting and diarrhea
- Bone Marrow -> anemia, blood clothing, immune deficiencies
Chemotherapy (CT)
- Antimetabolites: These mimic normal cellular molecules to disrupt metabolism, purine or pyrimidine analogs
- Alkylating Agents: Drugs like Cisplatin and Cyclophosphamide crosslink DNA strands (intra-strand or inter-strand), preventing the DNA double helix from separating for replication
- Plant-Derived Agents: These target microtubules. Taxol stabilizes microtubules to disrupt the mitotic spindle
- Antibiotics: Doxorubicin inserts itself into the DNA helix to inhibit topoisomerase, an enzyme that prevents excessive DNA twisting during replication
- Hormone Therapy: Used for hormone-dependent cancers. Tamoxifen blocks estrogen receptors in breast cancer, while Leuprolide suppresses androgen production for prostate cancer
Intefere with cell proliferation, good for cancer that already metastasized
Drug resistance
Mekanisme
- Pump out: Cancer cells may upregulate the MDR1 gene, which encodes P-glycoprotein. This protein acts as a pump, ejecting drugs from the cell before they can cause damage
- Block drugs
- Metabolize drugs using detoxifying enzymes
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Combination Strategies
- Immunotherapy + Radiotherapy (IRT)
- Abscopal Effect: Local radiation can trigger a systemic immune response, causing untreated distant tumors to shrink
- Radscopal Effect: Low-dose radiation can reshape the tumor microenvironment, increasing immune cell infiltration
- Mechanism: Radiation damages DNA, triggering the cGAS-STING pathway, which releases pro-inflammatory signals that turn "cold" (immune-ignorant) tumors into "hot" (immune-responsive) tumors
- Immunotherapy + Chemotherapy Certain chemotherapy drugs (e.g., Gemcitabine) can reduce immunosuppressive cells like myeloid-derived suppressor cells (MDSCs). Chemo can also induce immunogenic cell death, exposing markers like calreticulin that help dendritic cells recognize the tumor
Cancer and Aging
Older Cancer
Global health status of older people are heterogenous and older cancer patients are highly underrepresented in clinical trials this can cause:
- Overtreatment= Reduction of the quality of life without therapeutic benefit
- Undertreatment= Exclusion of older patients from viable therapeutic options
Comprehensive Geriartic Assesment= evaluasi menyeluruh kesehatan seseorang dari physycal performance, riwayat penyakit, riwayat obat, nutrisi, mental dll. Yang dibagi menjadi 3 klasifikasi :
- Fit: oriented towards standard treatment
- Vulnerable: they undergo adapted treatments
- Frail= given palliative care, make them feel better without attempt to cure it
High prevelence in older age due to
- Genomic instability
- Mutation accumulation
- ROS & DNA damage accumulation
- age associated mitocondrial dysfunction
- Epigenetic alterations
- progressive loss of cell identities
- enhance risk of carsinogenesis tumor heterogenity dan phenotypic plasticity
- Senecent Cell causing inflammatory env promote tumor growth by creating a tumorigenic environment
- Immune function decrease, progressive decay of immune function becomes less resilient and less effective.
- Chronic inflammation , hallmark of cancer
Chldern Cancer
Common cancer are Leukemia (2-5 yo), brain tumor (childhood) and non Hodgkin lymphoma (young adult) , bonemarrow and sarcoma ( mid adolesence)
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Reduced cancer in adults due to changes if lifestyle and screening programs
Reduced cancer i childern through early detection and advanced treatment
Caused of childhood cancer:
- genetic mutation
- Rare mutation and non mendeliat inheritance
- identifide single nucleotide polimorphism (SNP)
Inherent Risk Factor:
- Birth Weight
- Older parental age
- Conginital anomalies or birth defects
- Males has higher incidence of cancer
- environtment factor
- Karsinogenic process, radiation, air pollution
Future Direction:
- Molecular Epidemiology = Epigenetik mempelajari bagaimana lingkungan (polusi, dll.) dapat mengubah cara gen bekerja tanpa mengubah DNA.
- Tumor Biology= Setiap kanker anak tidak sama secara genetik, meskipun jenisnya sama.Studi besar menemukan banyak pola mutasi berbeda yang terkait usia, lingkungan, dan perbaikan DNA.
- Global Epidemiology = Perlu lebih banyak riset di negara menengah dan berkembang.
Future research in childhood cancer focuses on genetic and epigenetic factors, tumor genetic diversity, and global epidemiology. Advanced genetic methods help identify cancer risk and prenatal environmental exposures, while studying mutation patterns improves prevention and treatment strategies. Expanding research beyond high-income countries is important to better understand the causes of childhood cancer.
Cancer in chronic diseases:
- cancer, cardiovascular disease, diabetes, chronic kidney disease, and respiratory disease. Gouty arthritis marker
- chronic diseases and markers are equally important to cancer incidence as five major lifestyle factors
- five lifestyle factors (smoking, insufficient physical activity, insufficient fruit and vegetable intake, alcohol consumption, and obesity)
- 1/5 of cancer incidence and >1/3 of cancer deaths were attributable to the eight chronic diseases or markers.
Gene Therapy for Cancer
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immunotheraphy
CAR-T Cell Therapy This involves genetically engineering a patient's T cells to express Chimeric Antigen Receptors (CARs).
- Structure: CARs allow T cells to recognize tumor antigens independently of Major Histocompatibility Complex (MHC) molecules, overcoming a common immune escape mechanism
- Generations: The technology has evolved through five generations
- Manufacturing: The process involves leukapheresis (collecting T cells), T Cell Activation, genetic modification (inserting the CAR gene), expansion in the lab, QC, Persiapan pasien, and re-infusion
- Challenges: Risks include Cytokine Release Syndrome (CRS), neurotoxicity, and "antigen escape" (tumor stops expressing the target)
imune system recognize tumor using TAA, but tumor have ability to immune escape:
- Down regulating surface antigen expression
- Upregulating immune checkpoint surface to supress T cell activity
- secretion of immunosuppresive factor that inhibit immune cell in TME
- Monoclonal antibodies (mAbs) = consist of two terminal bindings fab (target) fc (immune system). so it works by either kill cancer dirrectly or facilitate activation of immune system to destroy it.
- minus: serious immune reaction and too large (inconvinience)
- theraupeutic mAbs : Non-conjugated mAbs, and Antibodies-Drug conjugated
- mAbs : biomarker menandai sel kanker untuk dihancurkan or block receptor
- Bispesific mAbs : menjadi jembatan
- Small Molecules : easy administration, high bioavailibility and safety, used for complement or alternative for mAbs
- Pd-1/Pd-L1 inhibitor used for inhibit immune checkpoints
- IDO1 inhibitor used for menginhibit ekspresi immune suppresion dalam TME
- Oncolytic virues: virus yang memperbanyak diri hanya di dalam cancer cell biar selnya meledak, klo sel meledak TAA cancer keluar dan mengaktifasi imun system, ex: HSV-1
- Cancer Vacciines: sel darah putih pasien diambil, terus di expose sama TAA cancer kalo udah kenal dan bisa lawan dimasukin lagi ke pasien biar sel imunnya punya immune memory dan serang cancer klo ketemu di badan
- Adoptive Cell Theraphy: Adoptive cell therapy is the transfer of autologous or allogeneic immune cells into a patient.
- Tumor infiltrating lymphocytes (TILs) = immune yg spesifik di jaringan tumor diambil, diperbanyak trus di masukin lagi
- Endogenous T cells= isolating and expanding antigen-specific T cells from the peripheral blood.
- T cell receptor (TCR)
- Chimeric antigen receptors (CARs)
TCR-T merupakan terapi sel T yang dimodifikasi untuk mengenali antigen tumor melalui molekul MHC, sehingga dapat mendeteksi antigen yang berasal dari protein intraseluler.
Sebaliknya, CAR-T menggunakan reseptor buatan yang memungkinkan sel T langsung mengenali antigen di permukaan sel tumor tanpa bergantung pada MHC, sehingga aktivasi sel T terjadi lebih cepat dan kuat.
CAR T Limitation:
- Antigen escape -> multiple targets
- Ontarget off target = mengenali protein + PTM spesific cancer
- Car T Cell trafiking and tumor infiltration= engineer penetration to phisiscal barier
- immunosupresive microenvirontment : combine with IT
- Car T associated toxicity = Car off switches
CRISPR Cas 9
- CRISPR adalah teknologi penyuntingan gen yang bekerja seperti gunting molekuler untuk memotong DNA di lokasi yang sangat spesifik.
- Has 2 componennts:
- A Guide RNA
- A protein complex Cas 9
- Cara Kerja:
- gRNA menempel pada Cas 9 membentuk complex CRISPR dgn bantuan tracrRNA
- CRISPR menmpel pada gen target, Cas9 menggunting 2 untai DNA
- perbaikan DNA menggunakan NHEJ (knokout gen) atau menggunakan HDR memungkinkan penyisipan atau perbaikan gen
- Limitation
- Long Term safety
- off target activity
- Ethical challenge
- manufucturing and delivering costs
SOAL UAS 2025
- Cancer prevelance in older age, kenapa efek samping di older people lebih parah?
- Mekanisme Oncogene inhibition dan relevansinya dengan cancer theraphy
- Gambar Histology, jelaskan karakteristik apa saja yang harus diperhatikan dari histology dan sistem grading bagaimana
- Riset terbaru yang kamu baca, latarbelakang, dasar theori dan kaitanya dengan gene therapy
SOAL UAS 2024
- ditanya CAR bedanya apa
- grading cancer materi bu nova
- perkembangan riset terkininya apa dan apa yang bisa dilakukan biologist
- kenapa prevalensi kanker di lansia lebih tinggi