MOLECULAR ONCOLOGY

• One of the leading causes of mortality worldwide
• Cancer


  NOT a single disease, but a group of diverse diseases (>100 types) with similar manifestations

  
• Symptoms of cancer


  • Difficulty of breathing → lung cancer
  • Bleeding, especially if the cancer / enlarging tumor erodes some of the blood vessels that surrounds a particular organ → esophageal cancer

  
• Cancer


  • Characterized by abnormal cell growth and potential to invade or spread to other parts of the body
  • Cancer defies many of the established principles that underlie normal cellular processes (i.e. cell growth and division, cell death, cell organization, and gene expression)

  
• Vogelstein cascade


  1. Stepwise chain of events (i.e. genetic mutations) leading to cancer development and progression

  2. Cancer does NOT happen overnight because there is a stepwise progression

  3. Each step in the pathway, there are genetic mutations that enable the development of phenotypes that are characteristic of cancer eventually leading to their progression

  
• Traditional cancer treatments


  • Surgery
  • Radiation therapy
  • Chemotherapy

  
• Surgery


  Allows the bulk excision of tumors
• Radiation


  Destroy DNA of cancer cells
• Chemotherapy (cytotoxic chemotherapeutic agents)


  Target rapidly dividing cells such as cancer cells

  
• Nowadays we benefit from a fourth pillar of cancer treatment → immunotherapy and targeted therapies

  
• Molecular Oncology aims at elucidating causative genetic changes and oncogenic pathways to develop novel therapeutic strategies, some of which have already entered clinical practice

  
• Neoplasm


  Literally "new growth," due to abnormal cell growth and division
• Cancer (from a pathologic perspective)


  A neoplasm

  
• Tumor classification based on behavior

  • Benign
  • Malignant

  
• Benign tumors


  Tumors in which cancer cells have not yet become invasive

  
• Benign tumors do not always remain benign, some cancers initially manifest as benign but later on become malignant

  
• Benign tumors


  • Adenoma
  • Myoma or leiomyoma

  
• Malignant tumors


  Cancer cells acquired the ability to invade surrounding tissue and distant sites as well → phenomena known as metastasis

  
• Malignant tumors


  • Adenocarcinoma
  • Leiomyosarcoma

  
• There are exceptions to the naming rule for benign and malignant tumors
• Exceptions to the naming rule

  • Teratoma
  • Melanoma
  • Seminomas
  • Lymphomas
• Carcinoma


  Cancers which are epithelial in origin (be it surface epithelium or glandular epithelium)

  
• Sarcoma


  Cancers from mesenchymal origin (e.g. connective tissue, muscle cells)
• Leukemia


  Cancers derived from white blood cells and their precursors

  
• Benign tumor cells do not cross or invade basal lamina, while malignant tumor cells cross or invade or breach the basal lamina

  
• Cancers are driven by two events: genetic mutations and epigenetic alterations

  
• Somatic mutations


  Mutations in the somatic cells
• Germ-line mutations


  Mutations that occur in the gametes, leading to heritable forms of cancer

  
• Cancer critical genes


  Genes whose mutation would lead to a phenotype that is characteristic of cancer

  
• Oncogenes


  Genes whose overexpression can stimulate the development of cancer; arise from mutations of protooncogenes

  
• Proto-oncogenes


  Normal genes that encode for proteins responsible for maintenance of normal cellular processes such as cell growth and cell division, cell death

  
• Intrinsic subtypes (based on gene expression profile)

  • Luminal
  • Basal
  • Normal cell-like
  • HER2-like
• Breast cancer treatment


  Tailored based on the molecular profile of breast cancer
• Lung cancer


  Most common cause of cancer-related mortality in both men and women
• Lung cancer


  • Identified based on distinct clinical, histologic, and molecular characteristics
  • Approximately 80% of lung cancers are related to carcinogens in tobacco smoke
• Types of lung cancer

  • Non-small cell lung cancer (NSCLC)
  • Small-cell lung cancer
• Non-small cell lung cancer (NSCLC)


  More common
• Therapeutic strategy for lung cancer

  Follows the same dictum as breast cancer
• Modern treatment approach for lung cancer

  Largely based on tumor mutational profile
• Tumor mutational profile


  Can give an appropriate targeted therapy