PART 4: Introduction to Cancer Treatment

Cancer cells are able to adapt quickly to treatment, making it harder to find strategies that consistently eliminate them.

Anti-tumor therapies target specific differences between cancer cells and healthy cells to minimize harm to healthy tissues.

Cancer cells have increased genome instability, which means they are more prone to mutations. This leads to a range of changes in their behavior, including rapid growth and resistance to treatments.

Cancer cells rapidly consume glucose for energy, a process called the Warburg effect, making them highly visible in PET scans that detect glucose uptake.

FDG-6P (Fluorodeoxyglucose-6-phosphate) is a radioactive molecule used in PET scans to detect tumors because it mimics glucose and is taken up by high-glucose consuming cancer cells.

The primary goal of tumor surgery is to remove as much of the tumor as possible, either completely or partially, while minimizing harm to healthy tissues.

Tumors that are well-defined, localized, and not invasive are more suitable for surgery because the risk of re-growth from remaining cells is lower.

A major limitation of surgery is that it can't address cancer cells that may have spread, making it a temporary solution as cancer can recur.

Anatomopathological analysis is used to evaluate the tumor tissue after surgery to identify the type of cancer, its stage, and its potential aggressive behavior.

Surgery offers less toxicity to normal cells compared to other therapies like chemotherapy and radiotherapy, making it a more tolerable treatment option.

Chemotherapy targets rapidly dividing cells, aiming to kill both cancer cells and healthy cells that also divide quickly.

Chemotherapy affects all rapidly dividing cells, including healthy tissues like hair follicles, bone marrow, and intestinal epithelium, leading to side effects.

Alkylating agents primarily target the S phase of the cell cycle when DNA replication occurs, interfering with DNA synthesis by cross-linking bases.

Alkylating agents work by disrupting the DNA structure by cross-linking DNA bases, leading to double-strand breaks.

Antimicrotubule agents, such as Vincristine, target the M (mitotic) phase of the cell cycle, interfering with microtubule assembly, which is essential for cell division.

Antimicrotubule agents work by primarily targeting the M phase, interfering with the process of mitosis (cell division) by disrupting microtubule assembly.

5-Fluorouracil (5-FU) is an example of a nucleotide analog used in chemotherapy that blocks DNA synthesis by competing with thymine.

Chemotherapy can damage rapidly dividing cells in the bone marrow, leading to pancytopenia, a condition characterized by low blood cell counts (red blood cells, white blood cells, and platelets).

Alkylating agents are considered the most toxic class of chemotherapy drugs due to their indiscriminate damage to both cancerous and healthy DNA, leading to severe side effects.

Intestinal epithelial damage caused by chemotherapy can lead to diarrhea and vomiting, as the rapidly dividing cells lining the intestines are also targeted.

Targeted therapy uses specific drugs or molecules to target only cancer-specific molecules or pathways, reducing harm to normal tissues.

Normal metabolic enzymes are not typically targeted by targeted therapy, as targeting them would affect healthy cells.

Monoclonal antibodies in targeted therapies bind to and block mutated surface receptors found on cancer cells, preventing their growth and signaling.

Anti-HER2 monoclonal antibody is used to target the HER2 receptor, commonly found in some breast cancers, to block their growth.

Targeted therapy can fail to target cancer cells in cases of very high heterogeneity, which is a diverse genetic make-up of the tumor, making the treatment less effective.

Immunotherapy involves using the patient's immune system to fight cancer by enhancing the body's natural defenses to recognize and attack cancer cells.

The four main types of immunotherapy are non-specific immunotherapy, vaccines, checkpoint inhibitors, and cellular therapy (e.g., CAR-T cells).

Immune checkpoint inhibitors block immune suppression mechanisms used by tumors to escape detection by the immune system, allowing the immune system to fight it.

Anti-PD1 therapies target the PD-1 receptor, found on T cells, and block the interaction of PD-1 with its ligand on tumor cells, restoring T-cell activity.

CAR-T cell therapy involves genetically engineering T cells to express a chimeric antigen receptor (CAR) that recognizes tumor-specific antigens, making them more effective in attacking cancer cells.

CAR-T therapy is highly specific and effective for blood cancers like leukemia and lymphoma, but it can be less effective against solid tumors and can cause severe side effects.

CAR-T therapy has shown promising results in treating blood cancers, especially leukemias and lymphomas, but it is still under development for solid tumors.

A CAR (chimeric antigen receptor) is created by fusing an antibody specific to a tumor antigen to a signaling domain, allowing T cells to recognize and attack tumor cells.

Cancer vaccines aim to educate the immune system to recognize and attack cancer-specific antigens, preventing future tumor growth or recurrence.

Immune checkpoint ligands expressed by tumors suppress immune system function by binding to receptors like PD-1 on T cells, allowing tumors to escape immune surveillance.

IL-2 (Interleukin-2) is a cytokine often used in non-specific immunotherapy to stimulate the growth and activation of T cells, enhancing the overall immune response.

Anti-CTLA-4 therapies work by blocking the CTLA-4 receptor on T cells, preventing its interaction with its ligand and reducing immune suppression, allowing T cells to attack tumors.

Checkpoint inhibitors directly enhance the activity of T cells by blocking the inhibitory signals that normally dampen their activity.

CAR-T cells are less effective against solid tumors because the dense matrix of solid tumors restricts their access to target antigens.

Finding specific antigens that are unique to solid tumors and not expressed by healthy cells is a major challenge in immunotherapy development, as it is necessary for effective immune targeting without damaging normal tissues.